Dosage of antibody drug conjugate rinatabart sesutecan

Abstract

The present invention relates to a method of treating a solid tumor by administering to a human subject an antibody-drug conjugate (ADC) comprising an antibody directed against FOLR1 conjugated to avixetecan via a hydrophilic linker. The ADC is administered at a dose of from 40 mg / m2 to 200 mg / m2. In one embodiment, the ADC is a conjugate rinatabart sesutecan (Rina-S), and in one embodiment, the ADC is a conjugate rinatabart sesutecan (Rina-S). The ADC can reduce tumor size when administered at specific doses and schedules and is effective to treat cancers that are resistant to standard therapies, such as radiation therapy, chemotherapy, or immunotherapy. The ADC can be used in combination with other anti-cancer drugs.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202480061222.6 (22) Application Date 2024.09.26 (30) Priority Data 63 / 585,585 2023.09.26 US 63 / 674,151 2024.07.22 US 63 / 691,804 2024.09.06 US (85) PCT International Application Entering National Phase Date 2026.03.24 (86) PCT International Application Application Data PCT / US2024 / 048613 2024.09.26 (87) PCT International Application Publication Data WO2025 / 072486 EN 2025.04.03 (71) Applicant: Jinmai Anbo Co., Ltd. Address: Valby, Copenhagen, Denmark (72) Inventors: Zhao Baiteng, Han Taixi (74) Patent Agency: Beijing Liushen Law Firm, 11105 Patent Attorney: Zhang Wenhui (51) Int.Cl. A61K 47 / 68 (2006.01) A61K 45 / 06 (2006.01) A61K 33 / 243 (2006.01) A61K 31 / 502 (2006.01) A61K 39 / 395 (2006.01) A61P 35 / 00 (2006.01) (54) Invention Name: Antibody-Drug Conjugate RINATABART The present invention relates to a method for treating solid tumors by administering an antibody-drug conjugate (ADC) to a human subject, the ADC comprising an antibody against FOLR1 conjugated to ezetine via a hydrophilic linker. The ADC is administered at a dose of 40 mg / m² to 200 mg / m². In one embodiment, the ADC is the conjugate rinatabart sesutecan (Rina-S). When administered at specific doses and schedules, the ADC can reduce tumor size and effectively treat cancers resistant to standard therapies such as radiotherapy, chemotherapy, or immunotherapy. The ADC can be used in combination with other anticancer drugs. Claims 3 pages Description 47 pages Sequence Listing (electronic publication) Drawings 16 pages CN 121909050 A 2026.04.21 CN 1 21 90 90 50 A

Claims

1. A method for treating solid tumors that are positive for folate receptor 1 (FOLR1), said method comprising administering 40 mg / m² 2 Up to 200mg / m 2 The dose of rinatabart sesutecan (Rina-S) was administered to human subjects with the aforementioned solid tumor.

2. The method according to claim 1, wherein the solid tumor is selected from the group consisting of ovarian cancer, endometrial cancer, breast cancer, lung cancer, and mesothelioma.

3. The method according to claim 1 or 2, wherein the solid tumor is ovarian epithelial carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma.

4. The method according to claim 1 or 2, wherein the solid tumor is endometrial cancer.

5. The method according to claim 1 or 2, wherein the solid tumor is ovarian cancer.

6. The method according to claim 1, wherein the solid tumor is: a) Non-small cell lung cancer (NSCLC); b) Breast cancer, including HER2-negative breast cancer; c) Pleural mesothelioma; or d) Peritoneal mesothelioma.

7. The method according to any one of the preceding claims, wherein the solid tumor is a platinum-resistant tumor, optionally a high-grade serous or endometrioid EOC, primary peritoneal carcinoma, or fallopian tube carcinoma resistant to platinum-based chemotherapy.

8. The method according to any one of the preceding claims, wherein the solid tumor is platinum-resistant ovarian cancer.

9. The method according to any one of claims 1-3 or 5, wherein the solid tumor is platinum-sensitive ovarian cancer.

10. The method according to any one of the preceding claims, wherein the solid tumor is localized or metastatic; and / or wherein at least one tumor is not surgically removable.

11. The method according to any one of the preceding claims, wherein Rina-S is at 60 mg / m² 2 Up to 180 mg / m 2 Dosage administration.

12. The method according to any one of the preceding claims, wherein Rina-S is at 100 mg / m² 2 Up to 140 mg / m 2 Dosage administration.

13. The method according to any one of the preceding claims, wherein Rina-S is at 100 mg / m² 2 Up to 120 mg / m 2 Dosage administration.

14. The method according to any one of the preceding claims, wherein Rina-S is at about 100 mg / m³ 2 Dosage administration.

15. The method according to any one of the preceding claims, wherein Rina-S is at about 120 mg / m³ 2 Dosage administration.

16. The method according to any one of the preceding claims, wherein the Rina-S dose is administered to the human subject once or twice a week on a schedule selected from the group consisting of: (i) once a week; (ii) every other week; (iii) one week of treatment followed by a two-week, three-week, or four-week break; (iv) two weeks of treatment followed by a one-week, two-week, three-week, or four-week break; (v) three weeks of treatment followed by a one-week, two-week, three-week, four-week, or five-week break; (vi) four weeks of treatment followed by a one-week, two-week, three-week, four-week, or five-week break; (vii) five weeks of treatment followed by a one-week, two-week, three-week, four-week, or five-week break; and (viii) once a month.

17. The method according to any one of claims 1-15, wherein the Rina-S dose is administered to the human subject at a cycle of once every three weeks (Q3W).

18. The method according to any one of claims 16-17, wherein the cycle is repeated 2, 4, 6, 8, 10, 12, 16 or 20 times.

19. The method according to any one of claims 1-18, wherein the human subject has previously been treated with at least one anticancer therapy, optionally wherein (a) The at least one anticancer therapy includes treatment with chemotherapy agents, and / or (b) wherein the subject had failed to respond to at least one of the anticancer therapies prior to treatment with Rina-S.

20. The method according to any one of the preceding claims, wherein Rina-S is administered in combination with one or more treatment modalities selected from the group consisting of: unconjugated antibodies, radiolabeled antibodies, drug-conjugated antibodies, toxin-conjugated antibodies, gene therapy, chemotherapy, therapeutic peptides, cytokine therapy, oligonucleotides, local radiotherapy, surgery, and interfering RNA therapy.

21. The method according to any one of the preceding claims, wherein Rina-S is applied as follows: (a) In combination with platinum-based chemotherapy, optionally with decarboplatin; (b) In combination with VEGF-based antagonist chemotherapy, optionally debevacizumab; or (c) Combined with a PD-1 inhibitor, optionally depembrolizumab.

22. The method according to any one of the preceding claims, wherein the treatment outcome of the subject is improved, optionally wherein... (a) The improved treatment outcome is selected from objective responses of disease stability, partial response, or complete response; (b) The improved treatment outcome described therein is a reduced tumor burden, and / or (c) The improved treatment outcome mentioned above is progression-free survival or disease-free survival.

23. A method of treating solid tumors, comprising administering rinatabart sesutecan (Rina-S) to a human subject with a solid tumor and any of the following: (i) platinum-based chemotherapy, such as carboplatin; (ii) an anti-angiogenic agent, such as an anti-VEGF antibody, such as bevacizumab; (iii) a PARP inhibitor, such as olaparib; or (iv) an immune checkpoint inhibitor, such as an inhibitor of the PD-1 or PD-L1 immune checkpoint protein, such as an anti-PD-1 antibody, such as pembrolizumab.

24. The method according to any one of the preceding claims, wherein Rina-S has the following structure (Structure 1): Ab is a folate receptor 1 (FOLR1) binding antibody containing a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the VH region and the VL region have the amino acid sequences shown in SEQ ID NO: 1 and SEQ ID NO: 2, respectively, and wherein n is 8.

25. The method of claim 24, wherein Ab is a FOLR1 binding antibody comprising a heavy chain containing the amino acid sequence shown in SEQ ID NO: 6 or optionally SEQ ID NO: 4, and a light chain containing the amino acid sequence shown in SEQ ID NO:

5.

26. The method according to any one of the preceding claims, wherein the Rina-S is administered to the human subject via intravenous administration.

27. The method according to any one of the preceding claims, wherein the FOLR1 expression level of the tumor has not been determined prior to the administration of Rina-S.

28. The method according to any one of claims 1-26, wherein, according to a regulatory-approved FOLR1 expression assay, optionally the Ventana FOLR1-2.1 RxDx Assay, the subject's tumor sample has high FOLR1 expression.

29. The method according to any one of claims 1-26, wherein, according to a regulatory-approved FOLR1 expression assay, optionally the Ventana FOLR1-2.1 RxDx Assay, the subject's tumor sample has intermediate or low FOLR1 expression.

30. The method according to any one of claims 1-26 and 28, wherein the human subject does not meet the criteria for treatment with somituximab.

31. Rinatabart sesutecan (Rina-S), which is used in a method of treating solid tumors, said method comprising administering 40 mg / m² 2 Up to 200 mg / m 2 For example, 60 mg / m 2 Up to 140 mg / m 2 For example, 100 mg / m 2 Or 120 mg / m 2 The Rina-S was administered to subjects with solid tumors at a dose specified in the text.

32. Use of Rinatabart sesutecan (Rina-S) in the preparation of a medicament for the treatment of solid tumors, wherein the medicament is used at a dose of 40 mg / m². 2 Up to 200 mg / m 2 For example, 60 mg / m 2 Up to 140 mg / m 2 For example, 100 mg / m 2 Or 120mg / m 2 The Rina-S dose was administered to a human subject suffering from the solid tumor.

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