Methods for determining treatment for prostate cancer

Abstract

This invention provides a method for assessing individuals with prostate cancer. [Solution] A method for treating prostate cancer in a subject or making a decision on the management of such treatment, comprising determining the presence or absence of one or more metastases in the subject using 18F-DCFPyL PET / CT, and treating the subject or making a decision on the management of treatment for the subject based on the presence or absence of one or more metastases, wherein the subject has metastatic or recurrent prostate cancer, or is suspected of having metastatic or recurrent prostate cancer.

Description

[Technical Field]

[0001] Related applications This application claims priority under Section 119 of the United States Patent Act to U.S. Provisional Application No. 62 / 744,400 filed on 11 October 2018, U.S. Provisional Application No. 62 / 754,520 filed on 1 November 2018, U.S. Provisional Application No. 62 / 804,081 filed on 11 February 2019, and U.S. Provisional Application No. 62 / 842,136 filed on 2 May 2019, the entire contents of each of these are incorporated herein by reference. [Background technology]

[0002] Background of the Invention Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in seven men will be diagnosed with prostate cancer in their lifetime. The American Cancer Society estimates that approximately 164,609 new cases of prostate cancer are diagnosed each year, and about 26,730 men will die from the disease. Approximately 2,900,000 men in the United States are currently among the prostate cancer survivors. New methods are needed to broaden treatment and management options. [Overview of the project]

[0003] In one aspect, a method for treating prostate cancer in a subject or for making decisions regarding the treatment and management thereof, 18A method is provided which includes determining the presence or absence of one or more metastases in a subject using F-DCFPyL PET / CT. In one embodiment of such a method, the method further includes treating the subject or making a treatment management decision regarding the subject based on the presence or absence of one or more metastases. In one embodiment of any one of the methods provided herein, the determination is based on obtaining or being given a result for any one of the assessment methods provided herein. In one embodiment of any one of the methods provided herein, the determination is based on performing any one of the assessment methods provided herein.

[0004] In one embodiment of any of the methods provided herein, the subject is any one of the subjects defined herein, such as having metastatic or recurrent prostate cancer, or suspected of having metastatic or recurrent prostate cancer. In one embodiment of any of the methods provided herein, the subject has an extraprostatic lesion, or is suspected of having metastatic or extraprostatic lesions. In one embodiment of any of the methods provided herein, the subject has pelvic (e.g., lymph node) metastasis, or is suspected of having pelvic (e.g., lymph node) metastasis. In one embodiment of any of the methods provided herein, the subject has distant metastasis, or is suspected of having distant metastasis. In one embodiment of any of the methods provided herein, the subject has nodular, bone, and / or visceral / soft tissue metastasis.

[0005] In one embodiment of any of the methods provided herein, one or more metastases are larger than 4 mm. In one embodiment of any of the methods provided herein, the median size of lymph node metastases is >4 mm. In any one of the methods provided herein, 18 F-DCFPyL is administered to the subject 1-2 hours before PET / CT. In one embodiment of any of the methods provided herein, 9 mCi (333 MBq) 18 F-DCFPyL is administered to the target patient via intravenous injection.

[0006] In one embodiment of any of the methods provided herein, the method further includes treating the subject based on the determination. In one embodiment of any of the methods provided herein, the treatment is any one of the treatments provided herein. In one embodiment of any of the methods provided herein, the method further includes making a treatment management decision. In one embodiment of any of the methods provided herein, making a treatment management decision includes one or more of the treatment management decisions provided herein.

[0007] In one embodiment of any of the methods provided herein, the subject has undergone a prior diagnostic test, such as a PSA test or a conventional imaging test. In one embodiment of any of the methods provided herein, the prior diagnostic test was a conventional imaging test that showed a negative or ambiguous finding for prostate cancer.

[0008] In one embodiment of any of the methods provided herein, the method further includes a step of performing an additional diagnostic test on the subject, such as a PSA test or a conventional imaging test. In one embodiment of any of the methods provided herein, the PSA test result was a detectable or elevated PSA in the subject after radical prostatectomy. In one embodiment of any of the methods provided herein, the PSA test result was an increase in PSA levels in the subject after radiotherapy, cryotherapy, or brachytherapy. [Brief explanation of the drawing]

[0009] [Figure 1] Figure 1 shows the OSPREY study design and cohort. [Figure 2] Figure 2 shows the diagnostic performance in pelvic lymph nodes.

Mode for Carrying Out the Invention

[0010] Detailed Description of the Invention This specification also refers to it as PyL 18 F-DCFPyL is a positron emission tomography / computed tomography (PET / CT) contrast agent that targets fluorinated PSMA and enables visualization of metastases such as bone and soft tissue metastases. Surprisingly, it has been found that imaging with such an agent can be used to determine the presence or absence of recurrent or metastatic prostate cancer in subjects as defined herein with a high level of sensitivity or positive intermediate degree.

[0011] The subjects defined herein are those having or suspected of having metastatic or recurrent prostate cancer in which PSMA is expressed. PSMA is a 100 kd type II membrane glycoprotein expressed in prostate tissue (Horoszewicz et al., 1987, Anticancer Res. 7:927-935; U.S. Patent No. 5,162,504). PSMA has been characterized as a type II transmembrane protein with sequence homology to the transferrin receptor (Israeli et al., 1994, Cancer Res. 54:1807-1811) and associated NAALADase activity (Carter et al., 1996, Proc. Natl. Acad. Sci. U.S.A. 93:749-753). PSMA is expressed in increased amounts in prostate cancer (Horoszewicz et al., 1987, Anticancer Res. 7:927-935; Rochon et al., 1994, Prostate 25:219-223; Murphy et al., 1995, Prostate 26:164-168; and Murphy et al., 1995, Anticancer Res. 15:1473-1479).

[0012] Surprisingly, it was also found that, in some embodiments, the identification of pelvic lymph node metastases larger than 4 mm provided even greater predictive power and sensitivity. Therefore, in any one of the methods provided herein, the subjects have (or are suspected of having) metastases, such as pelvic lymph node metastases larger than 4 mm.

[0013] When used herein, “metastatic” refers to primary cancer or cancer that has spread from a primary site. In prostate cancer, metastasis may occur outside the prostate. Metastasis may occur within the pelvis, such as in the pelvic lymph nodes, or in a site distant from the pelvis (also referred to herein as “distant metastasis”). In one embodiment of any one of the methods provided herein, metastasis is pelvic lymph node metastasis or metastasis to a other distant site. When used herein, "recurrent" refers to prostate cancer that occurs after the initial prostate cancer, or prostate cancer that has survived treatment.

[0014] In one aspect, a method for taking action on or making a decision on the management of any one of the subjects specified herein, 18 The method is provided, which includes identifying metastases in a subject using F-DCFPyL PET / CT imaging, and treating the subject or making a treatment management decision for the subject based on the presence or absence of identified metastases.

[0015] When used herein, “treatment” means any clinical activity that is taken or recommended to be taken in order to reduce or eliminate prostate cancer in a subject, or to provide any benefit to the subject, such as a reduction in symptoms resulting from having prostate cancer. Treatment of prostate cancer includes, but is not limited to, surgery, radiation therapy, cryotherapy, brachytherapy, chemotherapy, or hormone / androgen depletion therapy (ADT). In any of the methods provided herein, treatment or treatment of a subject may include, recommending, one of the forms of treatment provided herein, or providing such treatment to a subject.

[0016] In any one embodiment of the methods provided herein, the treatment or treatment of the subject comprises I-131 1095 in combination with enzalutamide. I-131 (iodine-131) 1095, a small molecule therapeutic agent, binds to the extracellular domain of PSMA. Preclinical data showed high tumor uptake and good tumor-versus-kidney discrimination, minimizing normal tissue dose while producing a lethal dose to the tumor. In a human prostate cancer mouse model, the compound, administered in single or multi-dose schedules, significantly reduced long-term tumor burden and enhanced survival without significant signs of toxicity. When used in a specially considered use setting, I-131 1095 significantly reduced PSA levels and bone pain, yet showed good tolerability in a group of heavily pre-treated patients with advanced prostate cancer.

[0017] The chemical structure of I-131 1095 (or 131I 1095) (i.e., 131I-(S)-2-(3((S)-1-carboxy-5-(3-(4-iodophenyl)ureido)pentyl)ureido)pentanedioic acid) is: [ka] That is the case.

[0018] Enantiomers, stereoisomers, rotational isomers, tautomers, diastereomers, or racemates thereof are also included in the definition of “I-131 1095”. U.S. Patent No. 8,487,129 describes such compounds, and those compounds and methods for producing them are incorporated herein by reference. In one embodiment, these compounds are for use in any one of the methods and compositions provided herein.

[0019] When used herein, "making a treatment management decision" means any decision that a clinician may make with respect to a subject having prostate cancer in order to monitor and / or treat the prostate cancer in that subject. Decisions regarding treatment management include, but are not limited to, deciding to perform a biopsy, changing the location of the biopsy, changing the frequency of the biopsy, deciding to perform surgery, changing the type of surgery, changing the location of the surgery, changing the timing of the surgery, deciding to administer radiation therapy, changing the type of radiation therapy, determining the dose of radiation therapy, determining the location of radiation therapy, changing the dose of radiation therapy, changing the location of radiation therapy, deciding to administer chemotherapy, changing the type of chemotherapy, determining the dose of chemotherapy, changing the dose of chemotherapy, changing the regimen for chemotherapy, deciding to administer hormone / ADT therapy, changing the type of hormone / ADT therapy, determining the dose of hormone / ADT therapy, changing the dose of hormone / ADT therapy, and changing the regimen for hormone / ADT therapy.

[0020] In any of the methods provided herein, the step of making a treatment management decision may include one or more of the steps described above. In any of the methods provided herein, the method may further include the step of treating or monitoring (or recommending treatment or monitoring) the subject in accordance with the treatment management decision.

[0021] Any subject of any one of the methods provided herein may have (or be suspected of having) metastatic or recurrent prostate cancer. In some embodiments of any one of the methods provided, the subject may have elevated or increased prostate-specific antigen (PSA) levels, such as those with elevated PSA levels exceeding 0.2 ng / mL above the lowest point (nadir). In some embodiments of such subjects, the subjects have undergone radiotherapy, cryotherapy, or brachytherapy. In some embodiments of any one of the methods provided herein, the subject has undergone radiotherapy, cryotherapy, or brachytherapy, or the method includes a step of treating the subject with radiotherapy, cryotherapy, or brachytherapy.

[0022] In some embodiments of any one of the methods provided, the subject may have high or elevated prostate-specific antigen (PSA) levels, such as a detectable or elevated PSA level of 0.2 ng / mL or higher with a confirmatory PSA level of 0.2 ng / mL or higher. In some embodiments of such subjects, the subject may have undergone radical prostatectomy. In some embodiments of any one of the methods provided herein, the subject may have undergone radical prostatectomy, or the method may include a step of treating the subject with radical prostatectomy.

[0023] In some embodiments of any one of the methods provided, a subject may have negative or ambiguous findings for prostate cancer by conventional imaging tests, such as conventional imaging tests performed as part of a standard therapeutic examination. Conventional imaging methods include, but are not limited to, pelvic CT / MRI, whole-body scans, NaF, flucyclovin, or choline PET. In some embodiments of any one of the methods provided herein, a subject may have undergone or the method may include a step of assessing the subject with conventional imaging. In some embodiment of any one of the methods provided herein, the subject is a person who has undergone a PSA level test, or the method includes a step of testing the PSA level in the subject.

[0024] In one embodiment of any of the methods provided herein, a subject had received prior antiandrogen therapy, such as with abiraterone. In another embodiment of any of the methods provided herein, such subject had received prior antiandrogen therapy, such as with abiraterone, but had not received prior cytotoxic chemotherapy, such as with taxane chemotherapy. In another embodiment of any of the methods provided herein, any one of such subjects has advanced prostate cancer despite these prior treatments (one or more). In another embodiment of any of the methods provided herein, any one of such subjects has advanced mCRPC despite these prior treatments (one or more).

[0025] In one embodiment of any of the methods provided herein, the subject had received multiple rounds of prior anti-androgen therapy, such as with abiraterone. In another embodiment of any of the methods provided herein, the subject had received prior anti-androgen therapy, such as with abiraterone, but had not received prior cytotoxic chemotherapy, such as with taxane chemotherapy. In another embodiment of any of the methods provided herein, any one of such subjects has prostate cancer that has progressed despite these prior treatments (one or more). In another embodiment of any of the methods provided herein, any one of such subjects has mCRPC that has progressed despite these prior treatments (one or more).

[0026] When used herein, “antiandrogen” refers to an agent that blocks (for example, inhibits) the action of androgenic hormones and androgenic regulatory molecules. Adrenergic receptor antagonists are considered antiandrogens herein. The term “antiandrogen” encompasses antiandrogens, antiandrogenic analogs, and antiandrogenic derivatives. In prostate cancer, antiandrogens block the activity of testosterone, which typically slows the growth of prostate cancer. In some embodiments, antiandrogens block the enzyme cytochrome P450 17A1, encoded by the CYP17A gene. Antiandrogens may be steroidal or non-steroidal (also referred to as “pure”). Examples of antiandrogenic substances include, but are not limited to, abiraterone (ZYTIGA®), enzalutamide (XTANDI®), nilutamide (NILANDRON®), flutamide (EULEXIN®), bicalutamide (CASODEX®), and orteronel (TAK-700, Tokai Pharmaceuticals, Inc.).

[0027] When used herein, “progression” refers to the proliferation of prostate cancer cells that have not been reduced by any of the preceding treatments or combinations thereof referred herein. Disease progression may be indicated by rising PSA levels (e.g., an increase of ≥25% from baseline or a preceding measurement, and a minimum of ≥2 ng / ml, accompanied or not accompanied by a second such assessment of progression ≥3 weeks later), disease progression of soft tissues as defined by RECIST 1.1, disease progression of bones as defined by two or more new lesions on a bone scan, and / or new pain in an area of ​​disease evident on a radiograph. In one embodiment of any one of the methods provided herein, the progressing prostate cancer is substantially unreduced by their preceding treatments or combinations and is considered unresponsive by a clinician.

[0028] In one aspect of any one of the methods provided herein, the subject had or had soft tissue or bone progression, such as by a scan showing progression relative to a comparative scan performed during a prior abiraterone treatment or after interruption from abiraterone. In one aspect of any one of the methods provided herein, the subject had or had soft tissue or bone progression, such as by a scan showing progression relative to the results of a previous scan performed during a prior abiraterone treatment or after interruption from abiraterone.

[0029] Example Example 1 - In patients with prostate cancer 18 A PrOspective Phase 2 / 3 Multi-Center Study of F-DCFPyL PET / CT Imaging - Examination of Diagnostic AccuracY 18 (OSPREY) Background Prostate-specific membrane antigen (PSMA) is a transmembrane protein overexpressed by prostate cancer (PCa) cells and can be targeted using the novel PET tracer 18 F-DCFPyL. This example aimed to determine the diagnostic performance of F-DCFPyL PET / CT for detecting pelvic lymph node metastases and other distant disease sites in men with PCa. 18

[0030] Methods In 385 men with high-risk PCa scheduled for radical prostatectomy and lymph node dissection (cohort A, n = 268) or with radiological evidence of metastatic PCa for whom biopsy was feasible (cohort B, n = 117), 18 ​F-DCFPyL PET / CT was evaluated. 9mCi (333MBq) 18 F-DCFPyL was administered 1-2 hours before PET / CT to detect pelvic lymph node metastasis. 18 Multiple coprimary endpoints, specifically the sensitivity and specificity of F-DCFPyL PET / CT, were evaluated in Cohort A. Secondary endpoints included safety in both cohorts, positive predictive value (PPV) and negative predictive value (NPV) in Cohort A, and sensitivity and PPV in Cohort B. Three central, blinded, and independent readers were selected. 18 F-DCFPyL scans were evaluated. Histopathology served as a reference criterion compared to imaging findings. Figure 1 provides information regarding the study design and cohort.

[0031] result In cohort A (n=252 are evaluable), 18 The sensitivity of F-DCFPyL PET / CT ranged from 30.6 to 41.9% among the three leaders (lower limit of 95% CI: 19.2 to 29.7%), with a specificity range of 96.3 to 98.9% (lower limit of 95% CI: 93.6 to 96.0%). In addition, PPV and NPV ranged from 78.1 to 90.5% and 81.4 to 83.8%, respectively. When the analysis was limited to lymph node metastases with a median >4 mm, there was a significant improvement in sensitivity (ranging from 51.7 to 65.5%; lower limit of 95% CI: 33.5 to 48.0%). In patients with distant metastatic PCa (Cohort B, n=93 evaluable), sensitivity and PPV values ​​ranged from 92.9–98.6% (lower limit of 95% CI: 84.0–91.6%) and 81.2–87.8%, respectively. No serious drug-related adverse events were observed, and 27 men (7.0%) experienced a drug-related adverse event of ≥1, with dysgeusia (2.1%) and headache (2.1%) being the most common.

[0032] Diagnostic performance overview (evaluable set) Overview of Pelvic Lymph Node Diagnosis • The specificity of the primary multiple endpoint was statistically significant across the range of 96–99% and at the pre-specified limit of 80%. • The second primary endpoint, sensitivity, ranged from 31% to 42% and did not meet the pre-specified confidence interval of 40%. • High PPV (78-91%) and NPV (81-84%) performance 18 This demonstrates the strong clinical practicality of F-DCFPyL PET / CT and provides physicians with the confidence to trust the test results. Metastasis Diagnosis Overview • Secondary efficacy endpoints representing recurrent or metastatic disease outside the pelvis (e.g., bone, soft tissue, and lymph nodes) • In this patient population, high sensitivity (93-99%) and PPV (81-88%) provide strong clinical utility for accurately detecting distant metastatic lesions.

[0033] Outline of Extraprostate Diagnosis • Detect extraprostatic lesions, including pelvic lymph nodes from extended pelvic lymph node dissection and distant metastatic or recurrent lesions from targeted biopsies. 18 The performance of F-DCFPyL was statistically significant across all diagnostic parameters. • This pooled analysis improves the overall sensitivity of PyL in detecting metastatic lesions (both pelvic and distant). Cohorts A and B Prostate Overview This is a preliminary endpoint demonstrating that PyL can detect prostate cancer with near-perfect sensitivity and PPV. • Confirm that these are high-risk prostate cancer patients.

[0034] A change in the medical management of the care in question (defined, for example, as a change in one or more of the following): Table 1 [Table 1]

[0035] Changes in management based on a series of centrally read pre-PyL imaging and clinical characteristics reviews followed by a re-review based on PyL imaging results. • In one case, changes in management were observed in approximately 43% of subjects after reviewing PyL PET / CT images, with the most significant changes being in planned hormone therapy. Cohort A

[0036] conclusion 18 F-DCFPyL PET / CT demonstrated good tolerability and high overall diagnostic performance in detecting pelvic lymph node metastases and other distant metastatic disease sites, as supported by its high specificity and PPV. These data suggest that this could enable more informed treatment choices in men with prostate cancer.

[0037] Example 2 - In a patient suspected of having recurrent prostate cancer 18 Research on F-DCFPyL PET / CT imaging (CONDOR) Table 2 [Table 2]

[0038] Performance Measurement Main outcome measurement: 1. 18 The Correct Localization Rate (CLR) is defined as the percentage of subjects with a one-to-one correspondence between at least one lesion identified on F-DCFPyL PET / CT imaging and a composite truth standard defined as either evaluable histopathology, informative correlative imaging, or PSA response after radiotherapy. Within 60 days following PyL PET / CT imaging, one or more suspected lesions caused by PyL are treated with biopsy / surgery, conventional imaging, or localized radiotherapy.

[0039] Secondary outcome measurement: 2. In the intended prostate cancer treatment plan 18 Percentage of subjects whose changes were caused by F-DCFPyL PET / CT imaging results. The intended changes to the prostate cancer treatment plan were based on Medical Management Questionnaires completed before and after PyL PET / CT imaging.

[0040] Eligibility Minimum age: 18 Maximum age: Gender: Male Gender-based: Yes - only male subjects will be enrolled in this study. Acceptance of healthy volunteers: None Criteria: Recruitment criteria: • Male > / = Age 18 • Prostate cancer confirmed histopathologically according to the original diagnosis, accompanied by subsequent curative treatment. • Suspected recurrence of prostate cancer based on elevated PSA levels after curative treatment based on the following: a. Post-radical prostatectomy: Detectable or elevated PSA of ≥0.2 ng / mL, accompanied by a confirmatory PSA of ≥0.2 ng / mL (American Urological Association [AUA]); or b. After radiotherapy, cryotherapy, or brachytherapy: Increased PSA levels exceeding 2 ng / mL (American Society of Radiation Oncology [ASTRO]-Phoenix) • Negative or ambiguous findings for prostate cancer in conventional imaging tests performed as part of standard treatment examinations within 60 days prior to day 1. • For each institutional standard treatment (SOC scan(s)(single or multiple) (e.g., pelvic CT / MRI, whole-body bone scan, NaF, flucyclovin, or choline PET), conventional imaging findings were completed within 60 days prior to day 1. SOC scans(single or multiple) performed more than 60 days prior to day 1 may be repeated as a screening procedure for the study and may be reviewed by the examiner before day 1. • Life expectancy ≥ 6 months as determined by the examining physician. • Ability and willingness to provide informed consent and comply with protocol requirements.

[0041] Exclusion criteria: • Subjects who were administered some kind of high-energy (>300KeV) gamma-ray emitting radioisotope within 5 physical half-lives relative to day 1. • Ongoing treatment with any systemic therapy for prostate cancer (e.g., ADT, anti-androgens, GnRH, LHRH agonists or antagonists) • Treatments performed in ADT during the past three months relative to day 1 • Having received treatment in a clinical trial for prostate cancer within 60 days prior to day 1. • Subjects who, in the opinion of the examining physician, have any medical condition or other circumstances that would compromise the safety or compliance of the subject in order to produce reliable data or to complete the study.

[0042] Example 3 - Results from the OSPREY Trial: In patients with prostate cancer 18 F-DCFPyL PET / CT Imaging Prospective Phase 2 / 3 Multicenter Study - Diagnostic Accuracy Testing background Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed by prostate cancer (PCa) cells. PSMA-based imaging is considered highly promising for PCa detection, and novel PET radiotrackers are also being used. 18It can be targeted using F-DCFPyL. This prospective multicenter trial aims to detect pelvic lymph node metastases and distant metastases in men with PCa. 18 Designed to determine the safety and diagnostic performance of F-DCFPyL PET / CT.

[0043] method In 385 men with high-risk PCa scheduled for radical prostatectomy with lymph node dissection (Cohort A), or those scheduled for biopsy with radiological evidence of recurrent or metastatic PCa (Cohort B), 18 F-DCFPyL PET / CT was evaluated. 9mCi (333MBq) 18 F-DCFPyL was administered 1-2 hours before PET / CT to detect prostate cancer metastases in the pelvic lymph nodes. 18 Multiple primary endpoints, including the sensitivity and specificity of F-DCFPyL PET / CT, were evaluated in Cohort A. The primary secondary endpoints included the incidence of adverse events and the detection of pelvic lymph node metastasis in Cohort A. 18 Positive predictive value (PPV) and negative predictive value (NPV) of F-DCFPyL PET / CT imaging for detecting prostate cancer within the site of metastasis or recurrence in Cohort B. 18 The sensitivity and PPV of F-DCFPyL PET / CT imaging were determined. Three central, blinded, and independent leaders were found to be... 18 F-DCFPyL scans were evaluated. Imaging findings were compared with histopathological findings, which served as a reference.

[0044] result Regarding the detection of pelvic lymph node metastasis in cohort A (n=252 evaluable), 18F-DCFPyL PET / CT imaging showed a median sensitivity of 40.3% (95% CI: 28.1–52.5%), a median specificity of 97.9% (95% CI: 94.5–99.4%), and median PPV and NPV of 86.7% (95% CI: 69.7–95.0%) and 83.2% (95% CI: 78.0–88.0%), respectively. In Cohort B (n=93 evaluable), the median sensitivity and PPV were 95.8% (95% CI: 87.8–99.0%) and 81.9% (95% CI: 73.7–90.2%), respectively. 18 The sensitivity and PPV of F-DCFPyL PET / CT were evaluated in Cohort B at different lesion locations at the regional level (prostate, pelvis, and extrapelvic region). The median sensitivity and PPV for the pelvic region were 100% (95% CI: N / A) and 79.5% (95% CI: 67.0–92.0%), respectively; and the median sensitivity and PPV for the extrapelvic region were 94.9% (95% CI: 82.0–99.0%) and 86.1% (95% CI: 76.0–96.0%), respectively. There were no evaluable subjects with local recurrence in the prostate region for analysis. Individual leader assessments are shown in the table below. No serious drug-related adverse events were observed. Twenty-seven men (7.0%) experienced drug-related adverse events of ≥1, with dysgeusia (2.1%) and headache (2.1%) being the most common.

[0045] conclusion 18 F-DCFPyL PET / CT has a favorable toxicity profile and was generally well-tolerated in patients with PCa. 18 F-DCFPyL PET / CT demonstrated high sensitivity in reliably detecting distant metastatic prostate cancer and high specificity in confirming the absence of pelvic lymph node metastasis in these disease settings. 18 The associated strong PPV and NPV of F-DCFPyL imaging suggests its potentially high clinical applicability. 18F-DCFPyL is currently being investigated in a Phase III trial in patients with biochemical relapses of PCa.

[0046] Table 3 Diagnostic performance by domain (Cohort B) [Table 3]

[0047] Example 4 - In the OSPREY Trial 18 Diagnostic performance of F-DCFPyL: In patients with known or suspected metastatic prostate cancer (mPC) (Pts) 18 F-DCFPyL PET / CT imaging prospective phase 2 / 3 multicenter study background Accurate detection of prostate cancer is essential for patient management, yet standard imaging methods still perform poorly in accurately detecting mPC. 18 F-DCFPyL is a novel PET contrast agent that selectively binds to prostate-specific membrane antigens, which are recognized targets for prostate cancer. OSPREY was a prospective, multicenter study in patients with either newly diagnosed high-risk prostate cancer (Cohort A) or known or suspected mPC (Cohort B). Here, we will focus on Cohort B.

[0048] method 117 men who were scheduled for a biopsy for recurrent or mPC 18 The patient underwent F-DCFPyL. An image-guided biopsy was then performed. 18 Sensitivity, positive predictive value (PPV), and safety of F-DCFPyL PET / CT were the primary endpoints for Cohort B. 18 F-DCFPyL PET / CT scans were evaluated by three independent, blinded, central leaders; and the results were compared with histopathology as the truth standard.

[0049] result When compared to histopathology 18 The sensitivity and PPV of F-DCFPyL PET / CT ranged from 92.9–98.6% (lower limit of 95% CI: 84.0–91.6%) and 81.2–87.8%, respectively. Diagnostic performance based on anatomical location showed high sensitivity and high PPV at all disease sites (see table below). Only two patients (1.7%) in Cohort B experienced drug-related adverse events (dysgeusia and generalized rash) of ≥1, both of which were mild in severity (grade 1).

[0050] conclusion 18 F-DCFPyL PET / CT demonstrated good tolerability and high sensitivity and PPV in accurately detecting nodal, bone, and / or visceral / soft tissue metastases. Positive 18 F-DCFPyL PET / CT scans have a high probability of revealing pathologically proven distant diseases, which is a positive influence on treatment planning as a PET imaging agent. 18 Demonstrate the potential of F-DCFPyL.

[0051] Table 4 [Table 4]

Claims

1. A method for treating prostate cancer in a subject or for making decisions regarding the management of such treatment: １８ To determine the presence or absence of one or more metastases in the subject using F-DCFPyL PET / CT, and To treat a subject or to make a decision regarding treatment management for a subject based on the presence or absence of one or more metastases. Includes, The method wherein the subject has metastatic or recurrent prostate cancer, or is suspected of having metastatic or recurrent prostate cancer.

2. The method according to claim 1, wherein the subject has an extraprostatic lesion or is suspected of having metastatic or extraprostatic lesions.

3. The method according to claim 1 or the present invention, wherein the subject has or is suspected of having pelvic metastasis.

4. The method according to any one of claims 1 to 3, wherein the subject has distant metastasis or is suspected to have distant metastasis.

5. The method according to any one of claims 1 to 4, wherein the subject has joint, bone, and / or visceral / soft tissue metastases.

6. The method according to any one of claims 1 to 5, wherein one or more of the metastases are larger than 4 mm.

7. The method according to claim 6, wherein the mean or median of lymph node metastases is >4 mm.

8. １８ The method according to any one of claims 1 to 7, wherein F-DCFPyL is administered to the subject 1 to 2 hours before PET / CT.

9. 9 mCi (333 MBq) １８ The method according to any one of claims 1 to 8, wherein F-DCFPyL is administered to the subject by IV injection.

10. The method according to any one of claims 1 to 9, further comprising treating the subject based on the aforementioned determination.

11. The method according to claim 9, wherein the treatment is any one of the treatments provided herein.

12. The method according to any one of claims 1 to 11, wherein making a treatment management decision includes one or more of the treatment management decisions provided herein.

13. The method according to any one of claims 1 to 12, wherein the subject is any one of the subjects described herein.

14. The method according to any one of claims 1 to 13, wherein the subject has undergone a prior diagnostic test, such as a PSA test or a conventional imaging test.

15. The method according to claim 13, wherein a prior diagnostic test showed negative or ambiguous findings for prostate cancer in a conventional imaging test.

16. The method according to any one of claims 1 to 15, further comprising the step of performing an additional diagnostic test on a subject, such as a PSA test or a conventional imaging test.

17. The method according to claim 16, wherein the PSA test result was a detectable or elevated PSA after radical prostatectomy in the subject.

18. The method according to claim 15, wherein the PSA test result is an increase in PSA level after radiotherapy, cryotherapy, or brachytherapy in the subject.

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