USE OF A COMPLEXED COMPOUND WITH A METAL, MEDICINE FOR CANCER TREATMENT, PHARMACEUTICAL COMPOSITION AND COMBINATION, AND KIT

Description

[001] This application claims priority under 35 U.S.C. § 119(e) of Provisional Application Serial No. U.S. 62 / 659,016, filed April 17, 2018, and Provisional Application Serial No. U.S. 62 / 670,442, filed May 11, 2018, the disclosures of which are incorporated herein in their entirety by reference. FIELD OF THE INVENTION

[002] The invention described relates to drug delivery conjugates for targeted therapy. The invention described in this document relates to methods of treating PSMA-expressing cancers with a compound of Formula 1. The invention described in this document also relates to methods of treating PSMA-expressing cancers with a compound of Formula 1 in patients resulting in stable disease after treatment with the compound of Formula 1. BACKGROUND

[003] Prostate-specific membrane antigen (PSMA) is a type II cell surface membrane-bound glycoprotein with a molecular weight of approximately 110 kDa, comprising an intracellular segment (amino acids 1-18), a transmembrane domain (amino acids 19-43), and an extensive extracellular domain (amino acids 44-750). Although the functions of the intracellular segment and transmembrane domains are currently considered insignificant, the extracellular domain is involved in several distinct activities. PSMA plays a role in the central nervous system. Petition 870260029766, dated 03 / 30 / 2026, page 7 / 127 2 / 49 tral, in which it metabolizes N-acetyl-aspartyl glutamate (NAAG) into glutamic acid and N-acetyl aspartic acid. Consequently, it is sometimes also referred to as an N-acetyl alpha-linked acid dipeptidase (NAALADase). PSMA is also sometimes referred to as folate hydrolase I (FOLH I) or glutamate carboxypeptidase (GCP II) due to its role in the proximal small intestine, where it removes γ-linked glutamate from poly-γ-glutamate folate and α-linked glutamate from peptides and small molecules.

[004] PSMA is named, in large part, due to its higher level of expression in prostate cancer cells; however, its particular function in prostate cancer cells remains elusive. PSMA is overexpressed in malignant prostate tissues when compared to other organs in the human body, such as the kidney, proximal small intestine, and salivary glands. Unlike many other membrane-bound proteins, PSMA undergoes rapid internalization into the cell in a manner similar to cell surface-bound receptors, such as vitamin receptors. PSMA is internalized via clathrin-coated wells and can subsequently recycle to the cell surface or go to lysosomes. It has been suggested that the dimer and monomer forms of PSMA are interconvertible, although direct evidence of interconversion is debated. Even so, only the PSMA dimer possesses enzymatic activity, and the monomer does not.

[005] Although the activity of PSMA on the cell surface of prostate cells remains under investigation, it has been recognized by the inventors in this document that PSMA represents a viable target for the selective and / or specific delivery of biologically active agents, including drug compounds, to such prostate cells. One such drug compound is Compound 1. Petition 870260029766, dated 03 / 30 / 2026, page 8 / 127 3 / 49 (also known as (3S,10S,14S)-3-[(naphthalen-2-yl)methyl]1,4,12-trioxo-1-[(1R,4S)-4-[[2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetamido]methyl]cyclohexyl]-2,5,11,13-tetra-azahexadecane-10,14,16-tricarboxylic acid) wherein 177Lu is complexed with the compound, useful for cancer treatment as described in document no. WO2015 / 055318. Compound 1 can be prepared according to the methods described in documents WO2015 / 055318, and WO2015 / 055318 is incorporated by reference for the preparation of Compound 1 as described in Example 3 and Example 5.

[006] Without being limited by theory, PSMA-617 is believed to consist of the pharmacophore ligand, glutamate-urea-lysine; the chelating agent DOTA (capable of complexing 177Lu); and a linker connecting these 2 entities. It is further believed that the urea-based binding motif allows the agent to bind to PSMA and be internalized at least at the site of disease.It is also believed that the binding of 177LuPSMA-617 leads to internalization via endocytosis and sustained retention of the ligand and its bound radioactive cargo within the cancer cell.

[007] Another compound is the PSMA 4 image conjugate Petition 870260029766, dated 03 / 30 / 2026, p. 9 / 127 4 / 49 (also known as 4,6,12,19-tetra-azadocosane-1,3,7tricarboxylic acid, 22-[3-[[[2-[[[5-(2-carboxyethyl)-2-hydroxyphenyl]methyl](carboxymethyl)amino]ethyl](carboxymethyl)amino]methyl]-4-hydroxyphenyl]-5,13,20trioxo-,(3S,7S)) wherein 68Ga (or a similar radioactive metal isotope) is complexed to the conjugate, useful for cancer imaging, as described in Eder M., Schafer M., Bauder-Wust U, Hull WE, Wangler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chern. 2012; 23: 688 to 697. The PSMA 4 imaging conjugate that can be prepared according to the methods described in (Eder, 2012), and (Eder, 2012) is incorporated by way of reference for the preparation of the PSMA 4 imaging conjugate, as described in the examples. SUMMARY

[008] In some embodiments, the present disclosure provides a method for treating cancer in a patient in need of such treatment comprising administering to the patient a therapeutically effective amount of Compound 1.

[009] In some embodiments, the present disclosure provides for the use of Compound 1 for the treatment of cancer in a patient. Petition 870260029766, dated 03 / 30 / 2026, page 10 / 127 5 / 49 In some respects, use involves administering a therapeutically effective amount of Compound 1 to the patient.

[0010] In some embodiments, the present disclosure provides the use of Compound 1 in the preparation of a medicament useful for the treatment of cancer in a patient. In some respects, the medicament comprises a therapeutically effective amount of Compound 1.

[0011] In some aspects of these modalities, the cancer is a PSMA-expressing cancer. In some aspects of these modalities, the compound is at least about 98 percent pure. In some modalities, the cancer is selected from the group consisting of a glioma, a carcinoma, a sarcoma, a lymphoma, a melanoma, a mesothelioma, a nasopharyngeal carcinoma, a leukemia, an adenocarcinoma, and a myeloma.

[0012] In some aspects of these modalities, cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, head cancer, neck cancer, cutaneous melanoma, intraocular melanoma, uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple-negative breast cancer, metastatic breast cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small bowel cancer, endocrine system cancer, thyroid gland cancer, parathyroid gland cancer, non-small cell lung cancer, adrenal gland cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic leukemia, acute leukemia, lymphocytic lymphomas, pleural mesothelioma, cancer of bladder, Burkitt's lymphoma, ureter cancer,kidney cancer, renal cell carcinoma, renal pelvis carcinoma, neo Petition 870260029766, dated 03 / 30 / 2026, page 11 / 127 6 / 49 Central nervous system (CNS) plasma cells, primary CNS lymphoma, spinal axis tumors, glioma, brainstem glioma, pituitary adenoma, and gastroesophageal junction adenocarcinoma. In some of these modalities, the cancer is a primary or secondary brain cancer. In some of these modalities, the cancer is prostate cancer. In some of these modalities, the cancer is metastatic prostate cancer.

[0013] In some aspects of these modalities, Compound 1 is administered in a parenteral dosage form. In some aspects of these modalities, the parenteral dosage form is selected from the group consisting of intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous, and intrathecal. In some aspects of these modalities, the therapeutically effective amount is from about 2 GBq to about 13 GBq. In some aspects of these modalities, the therapeutically effective amount is from about 4 GBq to about 11 GBq. In some aspects of these modalities, the therapeutically effective amount is from about 5 GBq to about 10 GBq. In some aspects of these modalities, the therapeutically effective amount is from about 6 GBq to about 9 GBq. In some aspects of these modalities, the therapeutically effective amount is from about 6.5 GBq to about 8.5 GBq. In some aspects of these modalities, the therapeutically effective amount is approximately 7 GBq to approximately 8 GBq.In some aspects of these modalities, the therapeutically effective amount is approximately 7.4 GBq. In some aspects of these modalities, the total dose ranges from approximately 15 GBq to approximately 200 GBq. In some aspects of these modalities, the total dose ranges from approximately 25 GBq to approximately 185 GBq. In some aspects of these modalities, the total dose ranges from approximately 35 GBq to approximately 150 GBq. In some aspects of these modalities, the total dose ranges from approximately 40 GBq to approximately... Petition 870260029766, dated 03 / 30 / 2026, p. 12 / 127 7 / 49 100 GBq. In some aspects of these modalities, the total dose is approximately 44 GBq. In some aspects of these modalities, the maximum duration of treatment for a subject is approximately 19 to 23 months.

[0014] In some aspects of these modalities, the therapeutically effective amount is 2 GBq to 13 GBq. In some aspects of these modalities, the therapeutically effective amount is 4 GBq to 11 GBq. In some aspects of these modalities, the therapeutically effective amount is 5 GBq to 10 GBq. In some aspects of these modalities, the therapeutically effective amount is 6 GBq to 9 GBq. In some aspects of these modalities, the therapeutically effective amount is 6.5 GBq to 8.5 GBq. In some aspects of these modalities, the therapeutically effective amount is 7 GBq to 8 GBq. In some aspects of these modalities, the therapeutically effective amount is 7.4 GBq.

[0015] In some aspects of these modalities, the therapeutically effective amount is from about 0.1 mg / m2 to about 6.0 mg / m2. In some aspects of these modalities, the therapeutically effective amount is from about 0.1 mg / m2 to about 5.0 mg / m2. In some aspects of these modalities, the therapeutically effective amount is from about 0.1 mg / m2 to about 4.0 mg / m2. In some aspects of these modalities, the therapeutically effective amount is from about 0.1 mg / m2 to about 3.5 mg / m2. In some aspects of these modalities, the therapeutically effective amount is from about 0.1 mg / m2 to about 3.0 mg / m2. In some aspects of these modalities, the therapeutically effective amount is from about 0.1 mg / m2 to about 2.5 mg / m2. In some aspects of these modalities, the therapeutically effective amount is approximately 0.1 mg / m2 to approximately 2.0 mg / m2.

[0016] In some aspects of these modalities, the therapeutically effective amount is about 0.1 mg / m2 to about 6.0 mg / m2. In some aspects of these modalities, the therapeutically effective amount Petition 870260029766, dated 03 / 30 / 2026, page 13 / 127 The therapeutically effective amount is approximately 0.1 mg / m2 to approximately 5.0 mg / m2. In some aspects of these modalities, the therapeutically effective amount is approximately 0.1 mg / m2 to approximately 4.0 mg / m2. In some aspects of these modalities, the therapeutically effective amount is approximately 0.1 mg / m2 to approximately 3.5 mg / m2. In some aspects of these modalities, the therapeutically effective amount is approximately 0.1 mg / m2 to approximately 3.0 mg / m2. In some aspects of these modalities, the therapeutically effective amount is approximately 0.1 mg / m2 to approximately 2.5 mg / m2. In some aspects of these modalities, the therapeutically effective amount is approximately 0.1 mg / m2 to approximately 2.0 mg / m2.

[0017] In other respects, the methods and uses described in this document also include imaging of PSMA expression by cancer. In some aspects of these modalities, the imaging step occurs before the administration step. In some aspects of these modalities, imaging is performed by SPECT imaging, with the imaging being selected from the group consisting of SPECT imaging, PET imaging, IHC, and FISH. In some aspects of these modalities, imaging is performed by SPECT imaging.

[0018] In some aspects of these embodiments, the imaging step comprises administering to the patient a PSMA ligand imaging conjugate of Formula 2 or a pharmaceutically acceptable salt thereof, wherein R' is hydrogen, or R' is selected from the group consisting of alkyl, aminoalkyl, carboxyalkyl, hydroxyalkyl, heteroalkyl, aryl, aryl Petition 870260029766, dated 03 / 30 / 2026, page 14 / 127 9 / 49 lalkyl and heteroarylalkyl, each of which is optionally substituted and wherein a radionuclide is attached to the conjugate.

[0019] In some aspects of these modalities, the imaging stage comprises the administration of a Formula 3 PSMA ligand imaging conjugate. or a pharmaceutically acceptable salt thereof, wherein R' is hydrogen, or R' is selected from the group consisting of alkyl, aminoalkyl, carboxyalkyl, hydroxyalkyl, heteroalkyl, aryl, arylalkyl and heteroarylalkyl, each of which is optionally substituted, and wherein M is a cation of a radionuclide. In some aspects of these embodiments, M in the conjugate, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of an isotope of gallium, an isotope of indium, an isotope of copper, an isotope of technetium and an isotope of rhenium. In some aspects of these embodiments, M in the conjugate, or a pharmaceutically acceptable salt thereof, is an isotope of technetium.

[0020] In some aspects of these modalities, the PSMA ligand imaging conjugate presents Formula 2a 2a or a pharmaceutically acceptable salt thereof, wherein a Petition 870260029766, dated 03 / 30 / 2026, page 15 / 127 10 / 49 dionuclide is linked to the conjugate. In some aspects of these modalities, the PSMA ligand imaging conjugate presents Formula 3a 3a or a pharmaceutically acceptable salt thereof.

[0021] In some aspects of these modalities, the imaging step comprises administering to the patient a Formula 4 PSMA binder imaging conjugate or a pharmaceutically acceptable salt thereof, wherein a radionuclide is attached to the conjugate. In some aspects of these modalities, the radionuclide is 68Ga.

[0022] In other respects, the methods and uses described in this document further include the determination of the patient's PSMA status by imaging. In some aspects of these modalities, the imaging is SPECT imaging. In some aspects of these modalities, the patient's PSMA status correlates with a Petition 870260029766, dated 03 / 30 / 2026, page 16 / 127 11 / 49 clinical benefit for the patient. In some aspects of these modalities, the clinical benefit is selected from the group consisting of tumor growth inhibition, stable disease, a partial response, and a complete response. In some aspects of these modalities, the clinical benefit is stable disease. In some aspects of these modalities, PSMA-positive lesions indicate functionally active PSMA.

[0023] In some aspects of these embodiments, the determination step comprises administering to the patient a PSMA ligand imaging conjugate of Formula 2 or a pharmaceutically acceptable salt thereof, wherein R' is hydrogen or R' is selected from the group consisting of alkyl, aminoalkyl, carboxyalkyl, hydroxyalkyl, heteroalkyl, aryl, arylalkyl and heteroarylalkyl, each of which is optionally substituted and wherein the conjugate is linked to a radionuclide.

[0024] In some aspects of these modalities, the determination step comprises the administration of a Formula 3 PSMA ligand imaging conjugate N. .COOH HOOC' INN - COOH H H H H H or a pharmaceutically acceptable salt thereof, wherein R' is Petition 870260029766, dated 03 / 30 / 2026, page 17 / 127 12 / 49 hydrogen, or R', is selected from the group consisting of alkyl, aminoalkyl, carboxyalkyl, hydroxyalkyl, heteroalkyl, aryl, arylalkyl, and heteroarylalkyl, each of which is optionally substituted, and wherein M is a cation of a radionuclide.

[0025] In some aspects of these embodiments, M in the conjugate, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of a gallium isotope, an indium isotope, a copper isotope, a technetium isotope, and a rhenium isotope. In some aspects of these embodiments, M in the conjugate, or a pharmaceutically acceptable salt thereof, is a technetium isotope. In some aspects of these embodiments, the PSMA ligand imaging conjugate has Formula 2a 2a or a pharmaceutically acceptable salt thereof, wherein a radionuclide is attached to the conjugate.

[0026] In some aspects of these modalities, the PSMA ligand imaging conjugate presents Formula 3a 3a or a pharmaceutically acceptable salt thereof.

[0027] In some aspects of these modalities, the determination step involves administering a combination to the patient Petition 870260029766, dated 03 / 30 / 2026, page 18 / 127 13 / 49 PSMA binder imaging of Formula 4 or a pharmaceutically acceptable salt thereof, wherein a radionuclide is attached to the conjugate. In some aspects of these modalities, the radionuclide is 68Ga.

[0028] In other embodiments, the present disclosure provides a method of treating cancer in a patient in need of such treatment comprising administering to the patient a therapeutically effective amount of Compound 1 177Lu is complexed with Compound 1, resulting in stable disease after Compound 1, or a pharmaceutically acceptable salt thereof, is administered. Petition 870260029766, dated 03 / 30 / 2026, page 19 / 127 14 / 49

[0029] In other embodiments, the present disclosure provides the use of a Compound 1 177Lu is complexed with Compound 1, resulting in stable disease after Compound 1, or a pharmaceutically acceptable salt thereof, is administered. In some aspects of these embodiments, use involves administering a therapeutically effective amount of Compound 1 to the patient.

[0030] In other embodiments, the present disclosure provides the use of a Compound 1 whereby 177Lu is complexed with Compound 1 in the preparation of Petition 870260029766, dated 03 / 30 / 2026, page 20 / 127 15 / 49 a useful medicine for the treatment of cancer in a patient, resulting in stable disease after Compound 1, or a pharmaceutically acceptable salt thereof, is administered. In some respects, the medicine comprises a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof.

[0031] In some aspects of these modalities, the patient has been treated with at least one prior treatment. In some aspects of these modalities, the at least one prior treatment is selected from the group consisting of systemic androgen axis therapy, a chemotherapeutic agent, surgery, radiotherapy, immunotherapy, photodynamic therapy, stem cell therapy, and hyperthermia. In some aspects of these modalities, the at least one prior treatment is a systemic treatment. In some aspects of these modalities, the systemic treatment is selected from the group consisting of palifosfamide, 5-fluorouracil, capecitabine, pemetrexed, cisplatin, carboplatin, gemcitabine, paclitaxel, vinorelbine, eribulin, docetaxel, cyclophosphamide, doxorubicin, regorafinibicin, and combinations thereof. In some aspects of these modalities, the cancer is a PSMA-expressing cancer.In some aspects of these forms, the compound is at least about 98 percent pure.

[0032] The embodiments of the invention are further described by the following enumerated clauses:

[0033] 1. A method for treating cancer in a patient in need of such treatment comprising administering to the patient a therapeutically effective amount of a compound of Formula 1 or 2 Petition 870260029766, dated 03 / 30 / 2026, page 21 / 127 16 / 49 whereby the compound is complexed with a metal.

[0034] 2. The method, according to clause 1, wherein the cancer is a cancer that expresses PSMA.

[0035] 3. The method according to clause 1 or 2, wherein the compound of Formula 1 is at least about 98 percent pure.

[0036] 4. The method, according to any of the preceding clauses, wherein the cancer is prostate cancer.

[0037] 5. The method, according to any of the preceding clauses, wherein the cancer is metastatic castration-resistant prostate cancer.

[0038] 6. The method, according to any of the preceding clauses, wherein the compound of Formula 1 is administered in a parenteral dosage form.

[0039] 7. The method, in accordance with clause 6, and the form of parenteral dosage is selected from the group consisting of intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous and intrathecal.

[0040] 8. The method, according to any of the clauses Petition 870260029766, dated 03 / 30 / 2026, p. 22 / 127 17 / 49 previous, with the therapeutically effective amount being from about 2 GBq to about 13 GBq.

[0041] 9. The method, according to any of the preceding clauses, wherein the therapeutically effective quantity is from about 4 GBq to about 11 GBq.

[0042] 10. The method, according to any of the preceding clauses, wherein the therapeutically effective quantity is from about 5 GBq to about 10 GBq.

[0043] 11. The method, according to any of the preceding clauses, wherein the therapeutically effective quantity is from about 6 GBq to about 9 GBq.

[0044] 12. The method, according to any of the preceding clauses, wherein the therapeutically effective quantity is approximately 6.5 GBq to approximately 8.5 GBq.

[0045] 13. The method, according to any of the preceding clauses, wherein the therapeutically effective quantity is approximately 7 GBq to approximately 8 GBq.

[0046] 14. The method, according to any of the preceding clauses, wherein the therapeutically effective quantity is approximately 7.4 GBq.

[0047] 15. The method, in accordance with any of the preceding clauses, which also includes imaging of PSMA expression by cancer.

[0048] 16. The method, according to clause 15, whereby imaging occurs before the administration stage.

[0049] 17. The method, according to clause 16, wherein the imaging is performed by imaging and wherein the imaging is selected from the group consisting of SPECT imaging, PET imaging, IHC and FISH.

[0050] 18. The method, according to clause 17, where the Petition 870260029766, dated 03 / 30 / 2026, page 23 / 127 18 / 49 Imaging is performed using SPECT imaging.

[0051] 19. The method, according to any of clauses 14, which also includes determining the patient's PSMA status by imaging.

[0052] 20. The method, according to clause 19, where the imaging is SPECT imaging.

[0053] 21. The method, in accordance with clause 20, whereby the patient's PSMA status correlates with a clinical benefit for the patient.

[0054] 22. The method, according to clause 21, wherein the clinical benefit is selected from the group consisting of tumor growth inhibition, stable disease, a partial response and a complete response.

[0055] 23. The method, according to clause 22, where the clinical benefit is stable disease.

[0056] 24. The method, according to clause 21, wherein at least one positive PSMA lesion indicates functionally active PSMA.

[0057] 25. The method, according to any of the preceding clauses, wherein the patient has been treated with at least one prior treatment.

[0058] 26. The method, according to clause 25, wherein at least one prior treatment is selected from the group consisting of systemic androgen axis therapy, chemotherapeutic agent, surgery, radiotherapy, immunotherapy, photodynamic therapy, stem cell therapy and hyperthermia.

[0059] 27. The method, according to clause 26, wherein at least one prior treatment is a systemic treatment with a drug of the geometric axis of androgen.

[0060] 28. The method, according to clause 26, wherein at least one prior treatment is selected from the group consisting Petition 870260029766, dated 03 / 30 / 2026, page 24 / 127 19 / 49 containing abiraterone, orteronel, galeterone, seviteronel, apalutamide, enzalutamide, and combinations thereof.

[0061] 29. The method, according to clause 25, wherein at least one prior treatment is selected from the group consisting of palifosfamide, 5-fluorouracil, capecitabine, pemetrexed, cisplatin, carboplatin, gemcitabine, paclitaxel, vinorelbine, eribulin, docetaxel, cyclophosphamide, doxorubicin, regorafinibicin and their combinations.

[0062] 30. The method, according to any of the preceding clauses, wherein the compound of Formula 1 is administered in combination with a second treatment.

[0063] 31. The method, according to clause 30, where the second treatment is the best supportive treatment.

[0064] 32. The method, in accordance with clause 30, where the second treatment is the best standard of care.

[0065] 33. The method, according to clause 30, where the second treatment is the best support / best standard of care.

[0066] 34. The method, according to clause 30, wherein the second treatment is a systemic treatment of the geometric axis of androgen.

[0067] 35. The method, according to clause 34, wherein the systemic treatment of the geometric axis of androgen is selected from the group consisting of abiraterone, orteronel, galeterone, seviteronel, apalutamide, enzalutamide and combinations thereof.

[0068] 36. The method, according to clause 30, where the second treatment is radiotherapy.

[0069] 37. The method, according to clause 30, wherein the radiotherapy is external beam radiotherapy (EBRT).

[0070] 38. The method, according to any of the preceding clauses, wherein the compound of Formula 1 is administered in a Petition 870260029766, dated 03 / 30 / 2026, page 25 / 127 20 / 49 schedule, once a week.

[0071] 39. The method, according to any of clauses 37, wherein the Formula 1 compound is administered on a schedule of once every 2 weeks.

[0072] 40. The method, according to any of clauses 1 to 37, wherein the Formula 1 compound is administered on a schedule of once every 3 weeks.

[0073] 41. The method, according to any of clauses 37, wherein the Formula 1 compound is administered on a schedule of once every 4 weeks.

[0074] 42. The method, according to any of clauses 37, wherein the Formula 1 compound is administered on a schedule of once every 5 weeks.

[0075] 43. The method, according to any of clauses 37, wherein the Formula 1 compound is administered on a schedule of once every 6 weeks.

[0076] 44. The method, according to any of clauses 37, wherein the Formula 1 compound is administered on a schedule of once every 7 weeks.

[0077] 45. The method, according to any of clauses 37, wherein the Formula 1 compound is administered on a schedule of once every 8 weeks.

[0078] 46. The method, according to any of clauses 37, wherein the Formula 1 compound is administered on a schedule of once every 4 to 6 weeks.

[0079] 47. The method, according to any of clauses 46, wherein the Formula 1 compound is administered for approximately 2 to 8 cycles of the schedule.

[0080] 48. The method, according to any of clauses 46, wherein the compound of Formula 1 is administered by approximately Petition 870260029766, dated 03 / 30 / 2026, p. 26 / 127 21 / 49 of 3 to 7 cycles of the schedule.

[0081] 49. The method, according to any of clauses 46, wherein the Formula 1 compound is administered for approximately 4 to 6 cycles of the schedule.

[0082] 50. The method, according to either of the preceding clauses, wherein the metal complexed with Compound 1 or with Compound 2 is selected from the group consisting of 90Y, 177Lu, 64Cd, 153Gd, 155Gd, 157Gd, 213Bi and 225Ac.

[0083] 51. The method, according to clause 50, wherein the metal complexed with Compound 1 is 177Lu.

[0084] 52. The method, according to clause 50, wherein the metal complexed with Compound 1 is 225Ac. BRIEF DESCRIPTION OF THE DRAWINGS

[0085] Figure 1 shows a schematic of the treatment method design. DEFINITIONS

[0086] According to the invention, functionally active PSMA means a cell surface membrane-bound glycoprotein that binds to a PSMA ligand. It will be noted that PSMA ligands are well known to those skilled in the art, such as those described in US Patent Publication No. 2010 / 0324008 A1, incorporated herein by reference.

[0087] According to the invention, clinical benefit means a patient's response to treatment with Compound 1, wherein response includes overall patient survival, ability to receive four or more cycles of therapy (e.g., four weeks of therapy) with Compound 1, inhibition of tumor growth, stable disease, a partial response and / or a complete response, among other clinical benefits defined by the Food and Drug Administration in the United States of America. Petition 870260029766, dated 03 / 30 / 2026, page 27 / 127 22 / 49

[0088] According to the invention, inhibition of tumor growth means reduction in tumor size, complete disappearance of a tumor, or growth of a patient's tumor by less than 30% over the course of therapy with Compound 1.

[0089] According to the invention, stable disease means no material progression of the disease in a patient over the course of therapy with Compound 1.

[0090] According to the invention, a partial response means a decrease in tumor size of 30% or more in a patient treated with Compound 1.

[0091] According to the invention, a complete response means the disappearance of detectable disease in a patient treated with Compound 1.

[0092] According to the invention, prior treatment means that the patient has been treated with at least one prior treatment known in the art. It will be noted that a prior treatment may be any treatment known to persons skilled in the art, including, but not limited to, chemotherapeutic agents, surgery, radiotherapy, immunotherapy, photodynamic therapy, stem cell therapy, hyperthermia and the like. Prior treatments may include systemic treatments, including, but not limited to, treatment with abiraterone, orteronel, galeterone, seviteronel, apalutamide, enzalutamide, palifosfamide, 5-fluorouracil, capecitabine, pemetrexed, cisplatin, carboplatin, gemcitabine, paclitaxel, vinorelbine, eribulin, docetaxel, cyclophosphamide, doxorubicin, regorafinib and combinations thereof.

[0093] According to the inventions, the term alkyl includes a chain of carbon atoms, which is optionally branched. It will be further understood that, in certain embodiments, alkyl is advantageously of limited length, including C1-C24, C1-C12, C1-C8, C1-C6 and Petition 870260029766, dated 03 / 30 / 2026, p. 28 / 127 23 / 49 C1-C4. Illustratively, such alkyl groups of particularly limited length, including C1-C8, C1-C6 and C1-C4, may be referred to as a lower alkyl group. It is noted in this document that shorter alkyl, alkenyl and / or alkynyl groups may add less lipophilicity to the compound and, consequently, will have different pharmacokinetic behavior. In embodiments of the invention described in this document, it should be understood in each case that the recitation of alkyl refers to alkyl as defined in this document and, optionally, to lower alkyl. Illustrative alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, 3-pentyl, neopentyl, hexyl, heptyl, octyl and the like. As used in this document, a carboxyalkyl group includes a combination of an alkyl group, as described in this document, with a carboxy group.As used in this document, a hydroxyalkyl group includes a combination of an alkyl group, as described in this document, with a hydroxy group. As used in this document, an aminoalkyl group includes a combination of an alkyl group, as described in this document, with an amino group.

[0094] According to the invention, the term heteroalkyl includes a chain of atoms that includes both carbon and at least one heteroatom, and is optionally branched. Illustrative heteroatoms include nitrogen, oxygen, and sulfur. In certain variations, illustrative heteroatoms also include phosphorus and selenium.

[0095] According to the invention, the term aryl includes monocyclic and polycyclic aromatic carbocyclic groups having from 6 to 14 carbon atoms in the ring, each of which may optionally be substituted. Illustrative aromatic carbocyclic groups described in this document include, but are not limited to, phenyl, naphthyl, and the like. According to the invention, the term hePetition 870260029766, dated 03 / 30 / 2026, p. 29 / 127 24 / 49 heteroaryl includes aromatic heterocyclic groups having 5 to 10 atoms in the ring, each of which may optionally be substituted. Illustrative aromatic heterocyclic groups include, but are not limited to, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, quinolinyl, quinazolinyl, quinoxalinyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, benzisoxazolyl, benzisothiazolyl and the like. According to the invention, the term heteroarylalkyl includes a combination of an alkyl group, as described herein, with a heteroaryl group described herein. According to the invention, the term arylalkyl includes a combination of an alkyl group, as described in this document, with an aryl group described in this document, for example, a benzyl group.

[0096] The term optionally substituted, as used in this document, includes the substitution of hydrogen atoms by other functional groups in the radical that is optionally substituted. These other functional groups include, but are not limited to, amino, hydroxyl, halo, thiol, alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, arylheteroalkyl, heteroaryl, heteroarylalkyl, heteroaryl-heteroalkyl, nitro, sulfonic acids and their derivatives, carboxylic acids and their derivatives, and the like. Illustratively, any of amino, hydroxyl, thiol, alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, arylheteroalkyl, heteroaryl, heteroarylalkyl, heteroarylheteroalkyl and / or sulfonic acid is optionally substituted.

[0097] According to the invention, the term administration, as used in this document, includes all means of introducing Compound 1 and PSMA ligand imaging conjugates described in this document to the patient, including, but not limited to, oral (po), intravenous (iv), intramuscular (im), subcutaneous (sc), trans Petition 870260029766, dated 03 / 30 / 2026, p. 30 / 127 25 / 49 dermal, inhalation, buccal, ocular, sublingual, vaginal, rectal and similar. Compound 1 and the PSMA ligand imaging conjugates described in this document may be administered in unit dose forms and / or formulations containing conventional non-toxic and pharmaceutically acceptable carriers, adjuvants and vehicles.

[0098] According to the invention, becquerel means a unit of radioactivity derived from the SI system, as is commonly understood by a person skilled in the art. One becquerel is defined as the activity of a quantity of radioactive material in which one nucleus decays per second. One becquerel is therefore equivalent to one inverse second, s-1. The becquerel is known to people skilled in the art as the successor to the curie (Ci), an older, non-SI unit of radioactivity based on the activity of 1 gram of radium-226. The curie is defined as 3.7 × 1010 s-1, or 37 GBq.

[0099] According to the invention, Curie or Ci means a unit of radioactivity named after the French physicist and chemist Marie Curie, as commonly understood by a person skilled in the art. The prefixes milli and micro are from the metric system and represent 0.001 and 0.000001, respectively. So, one millicurie (mCi) is 0.001 curie. One microcurie (pCi) is 0.000001 curie. DETAILED DESCRIPTION

[00100] According to the Applicant's invention described in this document, the embodiments of the numbered clauses provided in the summary above, or any combination thereof, are contemplated for combination with any of the embodiments described in the Detailed Description section of this patent application.

[00101] With reference to Figure 1, the design of the method can be described according to the scheme shown. In some embodiments, the stratification factors for the design include, but are not limited to. Petition 870260029766, dated 03 / 30 / 2026, p. 31 / 127 26 / 49 limited to, serum lactate dehydrogenase (LDH) (< / = 260 IU / L v. > 260 IU / L), presence of liver metastases, ECOG score (0-1 v. 2), inclusion of NAAD in best support / best standard of care, and similar outcomes. In some modalities, the primary outcome may be overall survival. In some modalities, secondary outcomes include, but are not limited to, radiographic progression-free survival (rPFS), RECIST response, time to first symptomatic skeletal event (SSE), and similar outcomes. In some modalities, additional secondary outcomes include, but are not limited to, safety and tolerability, heather-related quality of life (HRQoL; EQ-5D-5L, FACT-P, and Brief Pain Inventory - FORMA abbreviated [BPI-SF]), health economics, progression-free survival (PFS) (radiological, clinical, or PSA progression), biochemical response such as PSA levels, alkaline phosphatase level, and / or lactate dehydrogenase level.In some modalities, an outcome for the treatment methods described in this document may be a patient who achieved a reduction of ≥ 50% from baseline, confirmed by a second PSA measurement at ≥ 4 weeks. In some modalities, an outcome for the treatment methods described in this document may be a patient who achieved a reduction of ≥ 40% from baseline, confirmed by a second PSA measurement at ≥ 4 weeks. In some modalities, an outcome for the treatment methods described in this document may be a patient who achieved a reduction of ≥ 30% from baseline, confirmed by a second PSA measurement at ≥ 4 weeks.

[00102] In one embodiment, the methods described in this document can be used for applications in human and veterinary clinical medicine. Thus, a patient can be administered Compound 1 or PSMA ligand imaging conjugates described Petition 870260029766, dated 03 / 30 / 2026, p. 32 / 127 27 / 49 in this document and may be human or, in the case of veterinary applications, may be a laboratory, farm, domestic or wild animal. In one aspect, the patient may be a human being, a laboratory animal such as a rodent (e.g., mice, rats, hamsters, etc.), a rabbit, a monkey, a chimpanzee, domestic animals such as dogs, cats and rabbits, farm animals such as cows, horses, pigs, sheep, goats and wild animals in captivity such as bears, pandas, lions, tigers, leopards, elephants, zebras, giraffes, gorillas, dolphins and whales.

[00103] In some modalities, patients with positive PSMA tests may be randomized in a 2:1 ratio to receive Compound 1 plus best supportive / best standard of care or to receive best supportive / best standard of care alone. In some modalities, best supportive / best standard of care may be determined by the attending physician / investigator. In some modalities, best supportive / best standard of care may be determined by the attending physician / investigator but will exclude investigational agents, cytotoxic chemotherapy, other systemic radioisotopes, and hemibody radiotherapy. In some modalities, novel geometric androgen axis drugs [NAADs], such as abiraterone or enzalutamide, are permitted.

[00104] In some modalities, patients will be monitored throughout the 6- to 10-month treatment period for survival, disease progression, and adverse events. In some modalities, a long-term follow-up period may include collecting survival and treatment updates, assessing adverse events, as well as blood for hematology and chemistry tests.

[00105] In some modalities, the patient is 18 years of age or older. In some modalities, the patient is male. Petition 870260029766, dated 03 / 30 / 2026, page 33 / 127 28 / 49 In some modalities, the patient was previously diagnosed with prostate cancer. In some modalities, the patient was previously diagnosed with metastatic castration-resistant prostate cancer (mCRPC).In some modalities, the patient meets one or more criteria, selected from the group consisting of an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; a life expectancy of at least 6 months; histological, pathological, and / or cytological confirmation of prostate cancer; a positive 68Ga-PSMA-11 PET / CT scan; prior orchiectomy and / or ongoing androgen deprivation therapy and a serum testosterone castration level (<50 ng / dl or <1.7 nmol / l); has previously received at least one NAAD, such as enzalutamide and / or abiraterone; has previously been treated with at least 1 or 2 prior taxane regimens, with one taxane regimen comprising a minimum exposure of 2 cycles of a taxane, or has previously received only one taxane regimen, and a. the patient does not wish to receive a second taxane regimen, or b.The patient's physician considers him or her unsuitable to receive a second taxane regimen, for example, due to frailty assessed by geriatric assessment or health status or intolerance; progressive mCRPC, as documented progressive mCRPC based on at least one criterion, such as a. serum PSA progression defined as 2 consecutive increases in PSA relative to a previous baseline value measured at least 1 week prior, with the minimum baseline value being 2.0 ng / mL, b. soft tissue progression defined as a >20% increase in the sum of diameter (SOD) (short geometric axis for nodal lesions and long geometric axis for non-nodal lesions) of all target lesions based on the lowest SOD since treatment initiation or the appearance of one or more new lesions, and c. bone disease progression, such as assessable disease or new bone lesions by bone scan (2 + 2 criteria). Petition 870260029766, dated 03 / 30 / 2026, page 34 / 127 29 / 49 PCWG3); at least one metastatic lesion that is present on baseline CT, MRI, or bone scintigraphy imaging obtained <28 days prior to initiation of Compound 1 therapy; recovered to < Grade 2 of all clinically significant toxicities related to prior therapies such as prior chemotherapy, radiation, immunotherapy, and the like; adequate organ function, such as a. Bone marrow reserve including white blood cell (WBC) count > 2.5 x 10⁹ / µl (2.5 x 10⁹ / µl is equivalent to 2.5 x 10³ / µl and 2.5 x 10³ / µl and 2,500 / µl) or absolute neutrophil count (ANC) > 1.5 x 10⁹ / µl (1.5 x 10⁹ / µl is equivalent to 1.5 x 10³ / µl and 1.5 x 10³ / µl and 1,500 / µl), platelets > 100 x 10⁹ / µl (100 x 10⁹ / µl is equivalent to 100 x 10³ / µl and 100 x 10³ / µl and 100 x 10Λ3 / cumm and 100,000 / μl), and / or hemoglobin > 9 g / dl (9 g / dl is equivalent to 90 g / l and 5.59 mmol / l); b.Hepatic impairment, such as total bilirubin < 1.5 x institutional upper limit of normal (ULN) (for patients with known Gilbert's Syndrome, < 3 x ULN is permitted), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3.0 x ULN OR < 5.0 x ULN for patients with liver metastases, and renal impairment, such as serum creatinine < 1.5 x ULN or creatinine clearance > 50 mL / min; albumin > 3.0 g / dL (3.0 g / dL is equivalent to 30 g / L); and a stable bisphosphonate or denosumab regimen for > 30 days prior to treatment.

[00106] In some modalities, a patient may not receive treatment if the patient has had one or more of the following prior treatments with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, or hemibody irradiation within approximately 6 months prior to treatment; prior PSMA-targeted radioligand therapy; prior systemic anticancer therapy (e.g., chemotherapy, immunotherapy, or biological therapy [including monoclonal antibodies]) within approximately 28 days prior to treatment; prior administration of investigational agents within approximately 28 days prior to treatment; a hypersensitivity Petition 870260029766, dated 03 / 30 / 2026, page 35 / 127 30 / 49 of known interactions with the components of the therapy or their analogues; any other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy; a transfusion within approximately 30 days of treatment; a history of CNS metastases that have received therapy (surgery, radiotherapy, gamma-knife) and are neurologically stable, asymptomatic, and are not receiving corticosteroids for the purpose of maintaining neurological integrity; an overexamination as seen on baseline bone scintigraphy; symptomatic cord compression or clinical or radiological findings indicative of impending cord compression;Serious concurrent medical conditions (as determined by a physician), including but not limited to New York Heart Association class III or IV congestive heart failure, history of congenital long QT syndrome, uncontrolled infection, active hepatitis B or C, or other comorbid conditions that, in the investigator's opinion, would impair treatment or cooperation; or has been diagnosed with other malignancies that may alter life expectancy or interfere with disease assessment.

[00107] In various embodiments, the cancers described in this document may be a population of cancerous cells that is tumorigenic, including benign and malignant tumors, or the cancer may be non-tumorigenic. Cancer may arise spontaneously or through processes such as mutations present in the patient's germline or somatic mutations, or the cancer may be induced chemically, virally, or by radiation. Cancers applicable to the invention described in this document include, but are not limited to, glioma, carcinoma, sarcoma, lymphoma, melanoma, mesothelioma, nasopharyngeal carcinoma, leukemia, adenocarcinoma, and myeloma.

[00108] In some respects, cancers can be lung cancer Petition 870260029766, dated 03 / 30 / 2026, page 36 / 127 31 / 49 hand, bone cancer, pancreatic cancer, skin cancer, head cancer, neck cancer, cutaneous melanoma, intraocular melanoma, uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple-negative breast cancer, metastatic breast cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small bowel cancer, endocrine system cancer, thyroid gland cancer, parathyroid gland cancer, non-small cell lung cancer, adrenal gland cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic leukemia, acute leukemia, lymphocytic lymphomas, pleural mesothelioma, bladder cancer, Burkitt's lymphoma, ureter cancer, cancer of kidney, renal cell carcinoma, renal pelvis carcinoma,Neoplasms of the central nervous system (CNS), primary CNS lymphoma, spinal axis tumors, glioma, brainstem glioma, pituitary adenoma, and adenocarcinoma of the gastroesophageal junction.

[00109] Compound 1 has the formula where 177Lu is complexed with the compound. Petition 870260029766, dated 03 / 30 / 2026, page 37 / 127 32 / 49

[00110] In other embodiments, any one of a variety of PSMA ligand imaging conjugates detectable by PET imaging, SPECT imaging, and the like may be used. The exact imaging method is not limited to the imaging agents described in this document. Collectively, the PSMA ligand imaging conjugates useful for imaging described in this document, including those described by Formulas and the agents useful for PET imaging, SPECT imaging, etc., are referred to as PSMA ligand imaging conjugates.

[00111] In one embodiment, Compound 1 and the PSMA ligand imaging conjugates described herein bind to PSMA expressed in cancer cells. In an illustrative aspect, Compound 1 and the PSMA ligand imaging conjugates are able to differentially bind to PSMA in cancer cells compared to normal cells due to preferential expression (or overexpression) of PSMA in cancer cells.

[00112] In other embodiments of the methods described in this document, pharmaceutically acceptable salts of Compound 1 and PSMA ligand imaging conjugates described in this document are provided. The pharmaceutically acceptable salts of Compound 1 and PSMA ligand imaging conjugates described in this document include addition of acid and base salts thereof.

[00113] Suitable acid addition salts are formed from acids that form non-toxic salts. Illustrative examples include acetate, aspartate, benzoate, besylate, bicarbonate / carbonate, bisulfate / sulfate, borate, camsylate, citrate, esylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hydroxybenzate, hydrochloride / chloride, hydrobromide / bromide, iodide / iodide, isethionate, lactate, malate, maleate, malonate, mesylate, methylsulfate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, Petition 870260029766, dated 03 / 30 / 2026, page 38 / 127 33 / 49 phosphate / hydrogen phosphate / dihydrogen phosphate, saccharate, stearate, succinate, tartrate, tosylate and trifluoroacetate salts.

[00114] The suitable base salts of Compound 1 and the PSMA ligand imaging conjugates described in this document are formed from bases that form non-toxic salts. Illustrative examples include salts of arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine, and zinc. Hemissals of acids and bases may also be formed, for example, hemisulfate and hemicalcium salts.

[00115] In one embodiment, Compound 1 and the PSMA ligand imaging conjugates described in this document may be administered as a formulation in association with one or more pharmaceutically acceptable carriers. The carriers may be excipients. The choice of carrier will depend largely on factors such as the particular mode of administration, the effect of the carrier on solubility and stability, and the nature of the dosage form. Suitable pharmaceutical compositions for the delivery of Compound 1 and the PSMA ligand imaging conjugates described in this document and methods for their preparation will be readily apparent to those skilled in the art. Such compositions and methods for their preparation can be found, for example, in Remington: The Science & Practice of Pharmacy, 21st Edition (Lippincott Williams & Wilkins, 2005), incorporated herein by reference.

[00116] By way of illustration, a pharmaceutically acceptable carrier includes any and all solvents, dispersing media, coatings, antibacterial and antifungal agents, isotonic and absorption-retardant agents and the like, and combinations thereof, that are physiologically compatible. In some modalities Petition 870260029766, dated 03 / 30 / 2026, page 39 / 127 34 / 49 des, the carrier is suitable for parenteral administration. Pharmaceutically acceptable carriers include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. Additional active compounds may also be incorporated into the compositions of the invention.

[00117] In various embodiments, liquid formulations may include suspensions and solutions. Such formulations may comprise a carrier, for example, water, ethanol, polyethylene glycol, propylene glycol, methylcellulose or a suitable oil, and one or more emulsifying and / or suspending agents. Liquid formulations may also be prepared by reconstituting a solid.

[00118] In one embodiment, an aqueous suspension may contain the active materials mixed with appropriate excipients.Such excipients are suspending agents, for example, sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, tragacanth gum and acacia gum; dispersing or wetting agents which may be a naturally occurring phosphatide, for example, lecithin; a condensation product of an alkylene oxide with a fatty acid, for example, polyoxyethylene stearate; a condensation product of ethylene oxide with a long-chain aliphatic alcohol, for example, heptadecaethylene oxyethanol; a condensation product of ethylene oxide with a partial ester derived from fatty acids and a hexitol, such as polyoxyethylene sorbitol monooleate; or a condensation product of ethylene oxide with a partial ester derived from fatty acids and hexitol anhydrides, for example, polyoxyethylene sorbitan monooleate.Aqueous suspensions may also contain one or more preservatives, for example, ascorbic acid, ethyl, n-propyl or p-hydroxybenzoate; or one or more coloring agents. Petition 870260029766, dated 03 / 30 / 2026, p. 40 / 127 35 / 49

[00119] In an illustrative embodiment, dispersible powders and granules suitable for the preparation of an aqueous suspension by the addition of water provide the active ingredient in a mixture with a dispersing or wetting agent, a suspending agent, and one or more preservatives. Additional excipients, for example, coloring agents, may also be present.

[00120] Suitable emulsifying agents may be naturally occurring gums, for example, acacia gum or tragacanth gum; naturally occurring phosphatides, for example, soy lecithin; and esters including partial esters derived from fatty acids and hexitol anhydrides, for example, sorbitan monooleate, and condensation products of said partial esters with ethylene oxide, for example, polyoxyethylene sorbitan monooleate.

[00121] In other embodiments, isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol or sodium chloride, may be included in the composition. Prolonged absorption of injectable compositions may be achieved by including in the composition an agent that retards absorption, for example, monostearate salts and gelatin.

[00122] Illustrative formats for oral administration include tablets, capsules, elixirs, syrups and the like.

[00123] Depending on the type of cancer, as described in this document, the route of administration and / or whether Compound 1 and / or PSMA ligand imaging conjugates are administered locally or systemically, a wide range of permissible dosages are contemplated in this document, including doses falling in the range of about 1 pg / kg to about 1 g / kg. In some embodiments, permissible dosages are contemplated in this document in GBq units, including doses falling in the range of about 2 GBq to about 13 GBq. Dosages may be single or divided and po Petition 870260029766, dated 03 / 30 / 2026, p. 41 / 127 36 / 49 doses can be administered according to a wide variety of protocols, including qd, bid, tid, or even every other day, biweekly (biw), once a week, once a month, once a quarter, and so on. In each of these cases, it is understood that the therapeutically effective amounts described in this document correspond to the administration instance or, alternatively, to the total daily, weekly, monthly, or quarterly dose, as determined by the dosing protocol. In some embodiments, the compound of Formula 1 may be administered once a week, or once every two weeks, or once every three weeks, or once every four weeks, or once every five weeks, or once every six weeks, or once every seven weeks, or once every eight weeks, and so on.

[00124] In one aspect, a Compound 1 or a PSMA ligand imaging conjugate as described in this document can be administered directly into the bloodstream, muscle, or an internal organ. Suitable routes for such parenteral administration include intravenous, intra-arterial, intraperitoneal, intrathecal, epidural, intracerebroventricular, intraurethral, ​​intrasternal, intracranial, intratumoral, intramuscular, and subcutaneous administration. Suitable means for parenteral administration include needle injectors (including microneedle), needleless injectors, and infusion techniques.

[00125] In an illustrative aspect, parenteral formulations are typically aqueous solutions that may contain carriers or excipients such as salts, carbohydrates, and buffering agents (preferably at a pH of 3 to 9), but for some applications they may be more appropriately formulated as a sterile non-aqueous solution or as a dry form to be used in conjunction with a suitable vehicle such as sterile pyrogen-free water. In other embodiments, any of the liquid formulations described Petition 870260029766, dated 03 / 30 / 2026, p. 42 / 127 Section 37 / 49 in this document can be adapted for parenteral administration of Compound 1 or the PSMA ligand imaging conjugates described in this document. The preparation of parenteral formulations under sterile conditions, for example, by lyophilization under sterile conditions, can be easily performed using standard pharmaceutical techniques well known to those skilled in the art. In one embodiment, the solubility of a Compound 1 or a PSMA ligand imaging conjugate used in the preparation of a parenteral formulation can be increased by the use of appropriate formulation techniques, such as the incorporation of solubility-enhancing agents.

[00126] In various embodiments, formulations for parenteral administration can be formulated for immediate and / or modified release. In an illustrative aspect, the active agents of the invention (i.e., Compound 1 or the PSMA ligand imaging conjugates) can be administered in a time-release formulation, for example, in a composition that includes a slow-release polymer. The active Compound 1 or the PSMA ligand imaging conjugates can be prepared with carriers that will protect Compound 1 or the PSMA ligand imaging conjugate against rapid release, such as a controlled-release formulation, including microencapsulated implants and delivery systems. Biodegradable and biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, polylactic acid, and polyglycolic-polylactic copolymers (PGLA).The methods for preparing such formulations are generally known to those skilled in the art. In another embodiment, Compound 1 or the PSMA binder imaging conjugates described in this document, or compositions comprising Compound 1 or the imaging conjugates... Petition 870260029766, dated 03 / 30 / 2026, page 43 / 127 38 / 49 PSMA binder may be administered continuously, when appropriate.

[00127] In one embodiment, a kit is provided. If a combination of the active Compound 1 and the PSMA ligand imaging conjugates is administered, two or more pharmaceutical compositions may be combined in the form of a kit suitable for sequential administration or co-administration of the compositions. Such a kit comprises two or more separate pharmaceutical compositions, at least one of which contains a Compound 1 or PSMA ligand imaging conjugate described herein and means for separately retaining the compositions, such as a container, divided vial, or divided foil pack. In another embodiment, compositions comprising one or more of the Compound 1 or PSMA ligand imaging conjugates described herein are provided in containers with markers providing instructions for the use of Compound 1 or PSMA ligand imaging conjugates for patient selection and / or treatment.

[00128] In one embodiment, sterile injectable solutions can be prepared by incorporating the active agent in the required quantity into an appropriate solvent with one or a combination of ingredients described above, as needed, followed by sterilization by filtration. Typically, dispersions are prepared by incorporating the active Compound 1 or the PSMA ligand imaging conjugate into a sterile vehicle containing a dispersion medium and any additional ingredients of those described above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred preparation methods are vacuum drying and lyophilization, which yields a powder of the active ingredient plus any desired additional ingredient from a solution previously sterilized by filtration thereof, or the ingredients may be... Petition 870260029766, dated 03 / 30 / 2026, page 44 / 127 39 / 49 processed together by filtration.

[00129] The composition may be formulated as a solution, microemulsion, liposome or other ordered structure suitable for high drug concentration. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol and the like) and suitable mixtures thereof. In one embodiment, adequate fluidity may be maintained, for example, by the use of a coating such as lecithin, by maintaining the required particle size in the case of dispersion, and by the use of surfactants.

[00130] Any effective regimen for administering Compound 1 may be used. For example, Compound 1 may be administered in single doses, or the doses may be divided and administered as a multiple daily dose regimen. Additionally, a staggered regimen, for example, one to five days per week, may be used as an alternative to daily treatment, and for the purposes of the methods described in this document, such an intermittent or staggered daily regimen is considered equivalent to daily treatment and is contemplated. In one illustrative embodiment, the patient is treated with multiple injections of Compound 1 to treat cancer. In one embodiment, the patient is injected multiple times (preferably about 2 to about 50 times) with Compound 1, for example, at intervals of 12 to 72 hours or at intervals of 48 to 72 hours.Additional injections of Compound 1 may be administered to the patient at intervals of days or months after the initial injection (or initial injections), and the additional injections may prevent cancer recurrence.

[00131] Any suitable course of therapy with Compound 1 may be used. In one embodiment, individual doses and dosing regimens are selected to provide a total administered dose over one month of approximately 15 mg. In an illustrative example, the Petition 870260029766, dated 03 / 30 / 2026, page 45 / 127 40 / 49 Compound 1 is administered as a single daily dose five days a week, during weeks 1, 2, and 3 of each 4-week cycle, with no dose administered in week 4. Alternatively, Compound 1 is administered as a single daily dose three days a week, during weeks 1 and 3 of each 4-week cycle, with no dose administered in weeks 2 and 4. Alternatively, Compound 1 is administered bi-weekly during weeks 1 and 2, i.e., on days 1, 4, 8, and 11 of a 3-week cycle. Alternatively, Compound 1 is administered once a week during weeks 1 and 2, i.e., on days 1 and 8 of a 3-week cycle.

[00132] The daily unit dosage of Compound 1 may vary significantly depending on the patient's condition, the cancer being treated, the route of administration of Compound 1 and its distribution in tissues, and the possibility of co-use of other therapeutic treatments, such as radiotherapy or additional drugs in combination therapies. The effective amount to be administered to a patient is based on body surface area, mass, and the physician's assessment of the patient's condition. Therapeutically effective doses (also referred to in this document as the therapeutically effective amount) may range, for example, from about 0.5 mg / m2 to about 10.0 mg / m2.The therapeutically effective doses described in this document also include strips of approximately 0.5 mg / m2 to approximately 9.5 mg / m2, approximately 0.5 mg / m2 to approximately 9.0 mg / m2, approximately 0.5 mg / m2 to approximately 8.5 mg / m2, approximately 0.5 mg / m2 to approximately 8.0 mg / m2, approximately 0.5 mg / m2 to approximately 7.5 mg / m2, approximately 0.5 mg / m2 to approximately 7.0 mg / m2, approximately 0.5 mg / m2 to approximately 6.5 mg / m2, approximately 0.5 mg / m2 to approximately 6.0 mg / m2, approximately 0.5 mg / m2 to approximately 5.5 mg / m2, approximately 0.5 mg / m2 to approximately 5.0 mg / m2, approximately 0.5 mg / m2a close to 4.5 mg / m2, close to 0.5 mg / m2a close to 4.0 mg / m2, close. Petition 870260029766, dated 03 / 30 / 2026, page. 46 / 127 41 / 49 of 0.5 mg / m2a approximately 3.5 mg / m2, approximately 0.5 mg / m2a approximately 3.0 mg / m2, approximately 0.5 mg / m2a approximately 2.5 mg / m2, approximately 0.5 mg / m2a approximately 2.0 mg / m2, approximately 0.5 mg / m2a approximately 1.5 mg / m2, approximately 1.0 mg / m2a approximately 9.5 mg / m2, approximately 1.0 mg / m2a approximately 9.0 mg / m2, approximately 1.0 mg / m2a approximately 8.5 mg / m2, approximately 1.0 mg / m2a approximately 8.0 mg / m2, approximately 1.0 mg / m2a approximately 7.5 mg / m2, approximately 1.0 mg / m2a approximately 7.0 mg / m2, about 1.0 mg / m2a about 6.5 mg / m2, about 1.0 mg / m2a about 6.0 mg / m2, about 1.0 mg / m2a about 5.5 mg / m2, about 1.0 mg / m2a about 5.0 mg / m2, about 1.0 mg / m2a about 4.5 mg / m2, about 1.0 mg / m2a about 4.0 mg / m2, about 1.0 mg / m2a about 3.5 mg / m2, about 1.0 mg / m2a about 3.0 mg / m2, about 1.0 mg / m2a about 2.5 mg / m2, about 1.0 mg / m2a about 2.0 mg / m2e about 1.0 mg / m2a about 1.5 mg / m2.A person versed in the technique will readily observe that the therapeutically effective dose can vary within several ranges given above based on the factors mentioned above. The therapeutically effective dose for any particular patient or group of patients may be any numerical value between approximately 0.5 mg / m2 and approximately 10.0 mg / m2, including, but not limited to, 1.0 mg / m2, 1.5 mg / m2, 2.0 mg / m2, 2.5 mg / m2, 3.0 mg / m2, 3.5 mg / m2, 4.0 mg / m2, 4.5 mg / m2, 5.0 mg / m2, 5.5 mg / m2, 6.0 mg / m2, 6.5 mg / m2, 7.0 mg / m2, 7.5 mg / m2, 8.0 mg / m2, 8.5 mg / m2, 9.0 mg / m2, 9.5 mg / m2 and 10.0 mg / m2. The total dose may be administered in single or divided doses and may, at the physician's discretion, fall outside the typical range provided in this document.

[00133] In some modalities, the Formula 1 compound may be administered in combination with a second treatment. In some modalities, the second treatment is the best supportive treatment. In some modalities, the second treatment is the best standard of care. In some modalities, the se Petition 870260029766, dated 03 / 30 / 2026, page 47 / 127 42 / 49 Secondary treatment is the best supportive / best standard of care. In some modalities, secondary treatment is systemic geometric androgen axis therapy. In some modalities, systemic geometric androgen axis therapy is selected from the group consisting of abiraterone, orteronel, galeterone, seviteronel, apalutamide, enzalutamide, and combinations thereof. In some modalities, secondary treatment is radiotherapy. In some modalities, radiotherapy is external beam radiotherapy (EBRT).

[00134] The PSMA ligand image conjugates and Compound 1 described in this document may contain one or more chiral centers, or may be capable of existing as multiple stereoisomers. Consequently, it should be understood that the present invention includes pure stereoisomers as well as mixtures of stereoisomers, such as enantiomers, diastereomers, and enantiomerically or diastereomerically enriched mixtures. The PSMA ligand image conjugates and Compound 1 described in this document may be capable of existing as geometric isomers. Consequently, it should be understood that the present invention includes pure geometric isomers or mixtures of geometric isomers.

[00135] It is observed that the PSMA ligand and Compound 1 image conjugates described in this document may exist in non-solvated forms as well as in solvated forms, including hydrated forms. In general, the solvated forms are equivalent to the non-solvated forms and are included within the scope of the present invention. The PSMA ligand and Compound 1 image conjugates described in this document may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present invention and are intended to be within the scope of the present invention. Petition 870260029766, dated 03 / 30 / 2026, p. 48 / 127 43 / 49

[00136] In another embodiment, the compositions and / or dosage forms for administration of Compound 1 are prepared from Compound 1 with a purity of at least about 90%, or about 95%, or about 96%, or about 97%, or about 98%, or about 99%, or about 99.5%. In another embodiment, the compositions and / or dosage forms for administration of Compound 1 are prepared from Compound 1 with a purity of at least 90%, or at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99%, or at least 99.5%.

[00137] In another embodiment, the compositions and / or dosage forms for administration of the PSMA ligand imaging conjugate are prepared from the PSMA ligand imaging conjugate with a purity of at least about 90% or about 95%, or about 96%, or about 97%, or about 98%, or about 99% or about 99.5%. In another embodiment, the compositions and / or dosage forms for administration of the PSMA ligand imaging conjugate are prepared from the PSMA ligand imaging conjugate with a purity of at least 90%, or at least 95%, or at least 97% or at least 98%, or at least 99% or at least 99.5%.

[00138] In another embodiment, the compositions and / or dosage forms for administration of the radiolabeled PSMA ligand imaging conjugate are prepared from the PSMA ligand imaging conjugate with a radiochemical purity of at least about 90%, or about 95%, or about 96%, or about 97%, or about 98%, or about 99%, or about 99.5%. In another embodiment, the compositions and / or dosage forms for administration of the PSMA ligand imaging conjugate are prepared from the PSMA ligand imaging conjugate with a purity of at least 90%, or at least 95%, or at least Petition 870260029766, dated 03 / 30 / 2026, p. 49 / 127 44 / 49 96%, or at least 97%, or at least 98%, or at least 99%, or at least 99.5%.

[00139] The purity of Compound 1 or of the PSMA ligand imaging conjugates described in this document can be measured using any conventional technique, including various chromatographic or spectroscopic techniques, such as high-pressure or high-performance liquid chromatography (HPLC), nuclear magnetic resonance spectroscopy, TLC, UV absorbance spectroscopy, fluorescence spectroscopy and the like.

[00140] In another embodiment, Compound 1 or the PSMA ligand imaging conjugate described in this document is supplied in a sterile container or package.

[00141] In one aspect, a clinical benefit to the patient for treatment with Compound 1 can be characterized as overall survival (OS). As used in this document, the term overall survival (OS) means the time from the date of randomization to the date of death from any cause.

[00142] In one aspect, a clinical benefit to the patient from treatment with Compound 1 can be characterized using the Response Evaluation Criteria in Solid Tumors (RECIST). Illustratively, the criteria were adapted from the original WHO Manual (3), taking into account the measurement of the largest diameter for all target lesions: complete response (CR) — disappearance of all target lesions; partial response (PR) — decrease of at least 30% in the sum of the largest diameter of the target lesions, taking as reference the largest diameter of the baseline sum; stable disease (SD) — neither sufficient shrinkage to qualify as a partial response nor sufficient increase to qualify as progressive disease, taking as reference the smallest sum of the largest diameter since the beginning of treatment; progressive disease (PD) — increase of at least 20% Petition 870260029766, dated 03 / 30 / 2026, page 50 / 127 45 / 49 in the sum of the largest diameter of the target lesions, taking as a reference the smallest sum of the largest diameter recorded since the beginning of treatment or the appearance of one or more new lesions. In another aspect, the overall disease response rate (ORR) is a clinical benefit and is calculated as the percentage of patients who achieve a better response to CR or PR. The overall disease control rate (DCR) can be another clinical benefit and is calculated as the percentage of patients who achieve a better response to CR, PR, or SD. In some modalities, the response may be the disease control rate (DCR) measured by the RECIST v1.1 criteria.

[00143] In another aspect, a clinical benefit to the patient of treatment with Compound 1 may be characterized as radiographic progression-free survival (rPFS). As used in this document, radiographic progression-free survival (rPFS) means the time from the date of randomization to the date of radiographic disease progression, as described in the Prostate Cancer Working Group 3 (PCWG3) Guidelines, or death from any cause. See, for example, Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations from the Prostate Cancer Clinical Trials Work Group 3. J Clin Oncol 2016; 34(12): 1402–1418. In another aspect, a clinical benefit to the patient of treatment with Compound 1 may be characterized as time to first symptomatic skeletal event (SSE).It will be noted that a symptomatic skeletal event means a clinically significant pathological fracture, bone surgery or radiation, or spinal cord compression. As used in this document, time to first symptomatic skeletal event means the date of randomization until the date of the first new symptomatic pathological bone fracture, spinal cord compression, or orthopedic surgical intervention. Petition 870260029766, dated 03 / 30 / 2026, page 51 / 127 46 / 49 foot related to the tumor or need for radiotherapy to relieve bone pain, whichever occurs first.

[00144] In an illustrative example, overall survival is the time to death of a given patient, defined as the number of days from the first day the patient received protocol treatment (C1D1) until the date of the patient's death. All death events may be included, regardless of whether the event occurred while the patient was still taking the study drug or after the patient discontinued the study drug. If a patient did not die, the data may be censored at the last study visit, or the date of last contact, or the last date the patient was alive, whichever is last.

[00145] Alternatively, a clinical benefit to the patient as a result of treatment with Compound 1 may be characterized as the inhibition of tumor growth, which can be identified in a patient through, for example, follow-up imaging of the patient's cancer after treatment with Compound 1. For example, the inhibition of tumor growth may be characterized by measuring the size of tumors in a patient after administration of Compound 1 according to any of the imaging techniques described in this document, with the inhibition of tumor growth being indicated by a stable tumor size or a reduction in tumor size. It will be noted that the identification of tumor growth inhibition can be performed using a variety of techniques, and is not limited to the imaging methods described in this document (e.g., CT, MRI, PET imaging, SPECT imaging, or chest X-ray).

[00146] In one embodiment, a method is provided for determining whether Compound 1 is suitable for the treatment of a cancer patient, wherein the method comprises the step of determining the sta Petition 870260029766, dated 03 / 30 / 2026, page 52 / 127 47 / 49 tus of PSMA in a cancer patient, with Compound 1 being indicated for treatment if the patient's PSMA status is positive.

[00147] In one embodiment, a method is provided for evaluating whether Compound 1 is indicated for the treatment of a patient with one of the cancers described in this document. The method comprises the steps of visually determining the patient's PSMA status, wherein PSMA status is based on imaging tumors that are PSMA positive in the patient, and Compound 1 is indicated for the patient's treatment when the patient's PSMA status is positive.

[00148] In the modalities described above, if a patient is in the PSMA-positive status group, a clinical benefit of treatment with Compound 1 is indicated. In one modality, the clinical benefit for the patient may be overall patient survival, ability to receive four or more cycles of Compound 1 therapy, inhibition of tumor growth, stable disease, a partial patient response to therapy, a complete patient response to therapy, disease control (i.e., the best outcome achieved is a complete response, a partial response, or stable disease), and / or overall disease response (i.e., the best outcome achieved is a complete or partial response). In an illustrative example, the clinical benefit for a patient being treated for pleural mesothelioma or adenocarcinoma (e.g., adenocarcinoma of the gastroesophageal junction) is stable disease.

[00149] In another embodiment, the methods described in this document include the following examples. The examples also illustrate additional features of the various embodiments of the invention described in this document. However, it should be understood that the examples are illustrative and should not be interpreted as limiting or Petition 870260029766, dated 03 / 30 / 2026, p. 53 / 127 48 / 49 other embodiments of the invention described in this document. Furthermore, it is noted that other variations of the examples are included in the various embodiments of the invention described in this document. EXAMPLES EXAMPLE 1: A. Project:

[00150] Patients with positive PSMA tests were randomized in a 2:1 ratio to receive Composite 1 plus best support / best standard of care or to receive best support / best standard of care alone. Best support / best standard of care was determined by the attending physician / investigator. The study is open-label, and patients are monitored over a treatment period of 6 to 10 months for survival, disease progression, and adverse events. A long-term follow-up period includes collection of survival and treatment updates, assessment of adverse events, as well as blood for hematology and chemistry tests. During follow-up, patients are contacted every 3 months (± 1 month) by phone, email, or letter for 24 months or until the overall censoring rate for survival falls to a level identified in the SAP. B. Arm 1: Composite 1 plus best support / best standard of care (BS / BSOC)

[00151] Approximately 160 patients were randomized to receive the investigational product at a dose of 7.4 GBq (± 10%) of Compound 1 (dose is equivalent to 200 mCi) intravenously every 6 weeks (± 1 week) for a maximum of 6 cycles, plus best support / best standard of care (BS / BSOC). After 4 cycles, patients are evaluated for (1) evidence of response, (2) residual disease, and (3) tolerance to Compound 1. A saline flush with ≥ 10 mL of normal saline is administered to ga Petition 870260029766, dated 03 / 30 / 2026, page 54 / 127 49 / 49 Ensure intravenous line patency before administering 177Lu-PSMA-617. 177Lu-PSMA-617 was administered slowly intravenously through a permanent catheter and followed by flushing with saline solution. The administration time should be recorded. Total administered activity (GBq) should be measured. To date, patients have received between 1 and 6 cycles in the randomized arm. To date, approximately 320 patients have been examined with Ga-PSMA Conjugate 4 imaging. C. Arm 2: Best Support / Best Standard of Care (BS / BSOC) alone

[00152] Patients randomized for this purpose will receive the best support / best standard of care (BS / BSOC), as determined by the investigator. D. Outcome measurements:

[00153] Overall survival (OS) in patients with progressive PSMA-positive mCRPC receiving Composite 1 in addition to the best support / standard of care.

Claims

1. Use of a therapeutically effective amount of a compound of Formula 1, wherein the compound is complexed with a metal, said use being characterized by the fact that it is for the preparation of a medicament for the treatment of cancer in a patient in need of such treatment.

2. Use, according to claim 1, characterized in that the cancer is a cancer that expresses PSMA.

3. Use according to claim 1, characterized in that the compound of Formula 1 is at least about 98 percent pure.

4. Use according to claim 1, characterized in that the cancer is prostate cancer or metastatic castration-resistant prostate cancer.

5. Use, according to any one of claims 1 to 4, characterized in that the compound of Formula 1 is administered in a parenteral dosage form. Petition 870260066322, dated 06 / 07 / 2026, page 12 / 24 2 / 6 6. Use according to claim 5, characterized in that the parenteral dosage form is selected from the group consisting of intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous and intrathecal.

7. Use, according to any one of claims 1 to 4, characterized in that the therapeutically effective amount is from about 2 GBq to about 13 GBq, or from about 4 GBq to about 11 GBq, or from about 5 GBq to about 10 GBq, or from about 6 GBq to about 9 GBq, from about 6.5 GBq to about 8.5 GBq, or from about 7 GBq to about 8 GBq.

8. Use, according to any one of claims 1 to 4, characterized in that the therapeutically effective amount is about 7.4 GBq.

9. Use, according to any one of claims 1 to 4, characterized in that it further comprises the image of PSMA expression by cancer.

10. Use according to claim 9, characterized in that the imaging occurs before the administration step.

11. Use, according to claim 10, characterized in that the imaging is performed by imaging and that the imaging is selected from the group consisting of SPECT imaging, PET imaging, IHC and FISH.

12. Use, according to claim 11, characterized in that the imaging is performed by SPECT imaging.

13. Use, according to any one of claims 1 to 4, characterized in that it further includes determining the patient's PSMA status by imaging.

14. Use according to claim 13, characterized in that the imaging is SPECT imaging.

15. Use, according to claim 14, characterized by the fact that the patient's PSMA status correlates with a clinical benefit for the patient.

16. Use according to claim 15, characterized in that the clinical benefit is selected from the group consisting of tumor growth inhibition, stable disease, a partial response, and a complete response.

17. Use, according to claim 16, characterized in that the clinical benefit is stable disease.

18. Use, according to claim 16, characterized in that at least one PSMA-positive lesion indicates functionally active PSMA.

19. Use, according to any one of claims 1 to 4, characterized in that the patient has been treated with at least one prior treatment.

20. Use according to claim 19, characterized in that at least one prior treatment is selected from the group consisting of systemic androgen axis therapy, chemotherapeutic agent, surgery, radiotherapy, immunotherapy, photodynamic therapy, stem cell therapy and hyperthermia.

21. Use according to claim 20, characterized in that at least one prior treatment is a systemic drug treatment of the geometric axis of androgen.

22. Use according to claim 20, characterized in that at least one prior treatment is selected from the group consisting of abiraterone, orteronel, galeterone, seviteronel, apalutamide, enzalutamide and combinations thereof.

23. Use, according to claim 19, characterized in that at least one prior treatment is selected from the group consisting of palifosfamide, 5-fluorouracil, capecitabine, pemetrexed, cisplatin, carboplatin, gemcitabine, paclitaxel, vinorelbine, eribulin, docetaxel, cyclophosphamide, doxorubicin, regorafinib and combinations thereof.

24. Use, according to any one of claims 1 to 4, characterized in that the compound of Formula 1 is administered in combination with a second treatment.

25. Use according to claim 24, characterized in that the second treatment is the best supportive treatment.

26. Use according to claim 24, characterized in that the second treatment is the best standard of care.

27. Use according to claim 24, characterized in that the second treatment is the best supportive treatment / best standard of care.

28. Use according to claim 24, characterized in that the second treatment is a systemic treatment of the geometric axis of androgen.

29. Use according to claim 28, characterized in that the systemic treatment of the geometric axis of androgen is selected from the group consisting of abiraterone, orteronel, galeterone, seviteronel, apalutamide, enzalutamide and combinations thereof.

30. Use according to claim 24, characterized in that the second treatment is radiotherapy.

31. Use, according to claim 24, characterized in that the radiotherapy is external beam radiotherapy (EBRT).

32. Use, according to any of claims 1 to 4, characterized in that the compound of Formula 1 is administered on a schedule of once a week, or once every 2 weeks, or once every 3 weeks, or once every 4 weeks, or once every 5 weeks, or once every 6 weeks, or once every 7 weeks, or once every 8 weeks.

33. Use, according to any one of claims 1 to 37, characterized in that the compound of Formula 1 is administered on a schedule of once every 4 to 6 weeks.

34. Use according to claim 32 or 33, characterized in that the compound of Formula 1 is administered for about 2 to 8 schedule cycles, or about 3 to 7 schedule cycles, or about 4 to 6 schedule cycles.

35. Use, according to any one of claims 1 to 34, characterized in that the metal is selected from the group consisting of 90Y, 177Lu, 64Cd, 153Gd, 155Gd, 157Gd, 213Bi, and 225Ac.

36. Use according to claim 35, characterized in that the metal is 177Lu.

37. Use according to claim 35, characterized in that the metal is 225Ac.

38. A cancer treatment drug, characterized in that it comprises a therapeutically effective amount of a compound of Formula 1, as defined in claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant and / or vehicle.

39. Pharmaceutical composition, characterized in that it comprises a compound, as defined in claim 1, and a pharmaceutically acceptable carrier.

40. Pharmaceutical combination, characterized by comprising a composition, as defined in claim 38, and PSMA ligand imaging conjugates.

41. Kit for the treatment of cancer, characterized by Petition 870260066322, dated 06 / 07 / 2026, page 26 / 24 6 / 6 comprising: (a) a compound, as defined in claim 1; or (b) a pharmaceutical composition, as defined in claim 38; or (c) a pharmaceutical combination, as defined in claim 39; and (d) instructions for patient selection and / or treatment.

42. A method for treating cancer in a patient in need of such treatment, characterized in that it comprises administering to the patient a therapeutically effective amount of a compound of the formula ^OH in which the compound is complexed with a metal.

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