Metastatic Castration-Resistant Prostate Cancer
Conditions
Interventions
Patients in all cohorts will receive treatment with JNJ-63723283, 480 mg
administered intravenously every 4 weeks, and apalutamide, 240 mg orally each
day. Subjects will also remain on androgen depr
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Each potential subject must satisfy all of the following criteria to be enrolled in the study: 1. >=18 years of age 2. Criterion modified per Amendment 3 2.1 * Pathologically confirmed adenocarcinoma of the prostate on initial diagnosis * Pathologically confirmed t-SCNC (by screening biopsy of a metastatic site): Cohort 5 only 3. Criterion modified per Amendment 1 3.1 Metastatic disease as documented by technetium-99m (99mTc) bone scan or metastatic lesions by computed tomography (CT) or magnetic resonance imaging (MRI) scans (visceral or lymph node disease). CT-portion of PET/CT scan may be used for eligibility. If lymph node metastasis is the only evidence of metastatic disease, it must be >= 1.0 cm in the short axis and above the level of the iliac bifurcation. 4. Criterion modified per Amendment 1 4.1 Criterion modified per Amendment 4 4.2 Criterion modified per Amendment 5 4.3 Progression (all of the criteria below must be met): * PSA progression confirmed per Prostate Cancer Clinical Trials Working Group (PCWG3): Castration-resistant prostate cancer (CRPC) demonstrated during continuous ADT, defined as 2 rises of PSA, at least 1 week apart with the last PSA >=2 ng/mL. * PSA progression on AR-targeted therapy (abiraterone plus prednisone/prednisolone [AA-P]; apalutamide, darolutamide, or enzalutamide). * Radiographic progression of soft tissues according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) modified based on PCWG3, or radiographic progression of bone according to PCWG3. 5. Criterion modified per Amendment 2 5.1 Criterion modified per Amendment 3 5.2 Criterion modified per Amendment 4 5.3 Criterion modified per Amendment 5 5.4 Progressed while on therapy with AA-P, enzalutamide, darolutamide, or apalutamide. No washout is required, and no additional therapy may have been administered between discontinuation of AR-targeted the agents and study treatment. Subjects will be assigned to cohorts based on the results of the biomarker panel. Cohort 1: Biomarker-negative or biomarker-unknown subjects with adenocarcinoma (and not t-SCNC) who progressed on AA-P Cohort 2: Biomarker-negative or biomarker-unknown subjects with adenocarcinoma (and not t-SCNC) who progressed on apalutamide, darolutamide, or enzalutamide Cohort 3: Biomarker-positive subjects who progressed on AA-P Cohort 4: Biomarker-positive subjects who progressed on apalutamide, darolutamide, or enzalutamide Cohort 5: Biomarker-negative subjects with t-SCNC who progressed on treatment with AA-P, apalutamide, darolutamide, or enzalutamide Note: Prior docetaxel for HSPC is allowed; no washout is required. Note: Subjects who have developed t-SCNC and are biomarker-positive will be assigned to either Cohort 3 or 4, depending on therapy history. 6. Surgical or medical castration, with testosterone levels of <50 ng/dL. If the subject is being treated with GnRH analogs (subject who has not undergone bilateral orchiectomy), this therapy must have been initiated at least 4 weeks prior to first dose of study drug and must be continued throughout the study. 7. ECOG PS grade of 0 or 1 (see Attachment 2 for conversion from KPS) 8. Criterion modified per Amendment 3 8.1 Criterion modified per Amendment 4 8.2 Clinical laboratory values at Screening: a. Hemoglobi
Exclusion criteria
Exclusion criteria: 1. Criterion modified per Amendment 3 1.1 Initial diagnosis of primary prostatic neuroendocrine or small cell carcinoma. 2. Brain metastases. 3. Prior treatment with an anti-PD-1, anti-PD-L1, or anti CTLA-4 antibody. 4. Prior chemotherapy, except for docetaxel for HSPC. 5. Prior therapy with poly ADP-ribose polymerase (PARP) inhibitors. 6. Criterion modified per Amendment 5 6.1 Both prior abiraterone acetate plus prednisone/prednisolone (AA-P) and apalutamide, darotulamide or enzalutamide. 7. Criterion modified per Amendment 3 7.1 Therapies that must be discontinued or substituted at least 4 weeks prior to first dose of study drug include the following: * Medications known to lower the seizure threshold (see Prohibited Medications) * Herbal and non-herbal products that may decrease PSA levels (eg, megestrol, 5a- reductase inhibitors). 8. Criterion modified per Amendment 3 8.1 Any investigational agent for the treatment of castration-resistant prostate cancer 9. If a subject has undergone major surgery, they must have recovered adequately from the toxicities or complications from the intervention within 4 weeks prior to starting therapy. 10.History of any of the following: * Seizure or known condition that may pre-dispose to seizure (including but not limited to: stroke, transient ischemic attack, or loss of consciousness within 1 year prior to first dose of study drug, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect) * Active malignancies (ie, requiring treatment change in the last 24 months) other than urothelial cancer (except skin cancers within the last 24 months that are considered completely cured). * Any of the following within 6 months prior to first dose of study drug: Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association (NYHA) Class II to IV heart disease; uncomplicated deep vein thrombosis (DVT) is not considered exclusionary 11. Criterion modified per Amendment 3 11.1 Criterion modified per Amendment 4 11.2 Uncontrolled hypertension (2 or more readings of blood pressure at the clinic that are above: systolic >=160 mmHg or diastolic >=100 mmHg) 12. Gastrointestinal disorder affecting absorption. 13. Active infection or conditions requiring treatment with antibiotics. 14. Has taken immunosuppressive doses of systemic medications, such as corticosteroids (doses >10 mg/day prednisone or equivalent), within 2 weeks before first dose of study drug. 15. Active autoimmune disease or a documented history of autoimmune disease that requires immunosuppressive medications (eg, chronic steroids, methotrexate, tacrolimus, etc.). Note: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with a history of transient autoimmune manifestations of an acute infectious disease that resolved upon treatment of the infectious agent (eg,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| # Incidence and severity of adverse events. # PSA response rate at 12 weeks in all-treated subjects. | — |
Secondary
| Measure | Time frame |
|---|---|
| # Maximal PSA decline in all-treated subjects. # Circulating tumor cell (CTC) response. | — |
Countries
Netherlands
Outcome results
None listed