A Study of PSMA ADC in Subjects With Metastatic Castration-resistant Prostate Cancer (mCRPC)

Study Overview
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Brief Summary
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PSMA ADC 2301 is a Phase 2, open-label, study to assess the anti-tumor activity and tolerability of Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) in two groups of subjects with metastatic castration-resistant prostate cancer (mCRPC). One group comprises subjects who must have received at least one taxane-containing chemotherapy regimen (e.g. docetaxel, cabazitaxel). The second group comprises subjects who are cytotoxic chemotherapy-naïve. Subjects who are cytotoxic chemotherapy-naïve must have received and progressed on-, be ineligible for, refused, have an intolerance to-, or not have access to Radium-223. Both groups of subjects must also have received and progressed on abiraterone acetate and/or enzalutamide. If a subject is unable to receive abiraterone acetate and/or enzalutamide, Sponsor approval is required for participation in the study. Subjects will receive up to eight doses of PSMA ADC approximately once every three weeks.

Official Title
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A Phase 2, Open-label, Multicenter Study of PSMA ADC in Subjects With Metastatic Castration-resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: PSMA ADC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of metastatic castration-resistant prostate cancer. a) Prior history of treatment with at least one taxane-containing chemotherapy regimen (e.g. docetaxel, cabazitaxel). If a subject has received more than two cytotoxic chemotherapy regimens, Sponsor approval is required for study participation. OR b) No prior history of treatment with a cytotoxic chemotherapy regimen. Must have received and progressed on abiraterone acetate and/or enzalutamide. If subject is unable to receive abiraterone acetate and/or enzalutamide, Sponsor approval is required for participation in the study. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Life expectancy ≥ six months. Cytotoxic chemotherapy-naïve subjects ONLY must have received and progressed on-, be ineligible for, refused, have an intolerance to-, or not have access to Radium-223. Exclusion Criteria: Treatment within 30 days prior to first dose of study drug of the following: External Radiation therapy Radiopharmaceuticals Cytotoxic chemotherapy Treatment with an investigational agent Clinically significant cardiac disease or severe debilitating pulmonary disease An acute infection requiring ongoing antibiotic therapy Any prior treatment with PSMA ADC or other therapies targeting PSMA, or other antibody drug conjugate (ADC) products that contain monomethyl auristatin E (MMAE) (e.g., brentuximab vedotin, glembatumumab vedotin, ASG-5ME, RG7450) unless approved by Sponsor. History of drug and/or alcohol abuse History of pancreatitis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: PSMA ADC<br>Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) administered IV at 2.5 mg/kg Q3W for 8 cycles or 2.3 mg/kg Q3W for 8 cycles. | Drug: PSMA ADC<br>* PSMA ADC administered IV at 2.5 mg/kg Q3W for 8 cycles or 2.3 mg/kg Q3W for 8 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Total Serum PSA Response | Total serum prostate-specific antigen (PSA) response was defined as any decrease from baseline of at least 30% or 50%. | 24 Weeks | 
| CTC Response | Circulating tumor cells (CTC) response was examined at two levels: at least 30% decrease or at least 50% decrease in CTC levels. Response was defined as any decrease from baseline of at least 30% or 50%. | 24 Weeks | 
| Overall Radiologic Response | Overall radiologic response was measured prior to the first dose of study drug, at predose of cycle 5, and at the end of study. Imaging techniques used at screening were used throughout the study. The preferred imaging techniques include: bone scan, contrast enhanced CT of chest, contrast enhanced CT of pelvis, and contrast enhanced CT of upper & lower abdomen. Best overall radiologic response (confirmed), target and non-target lesions, was defined as responses in bone, visceral or nodal metastases according to the Modified Response Evaluation Criteria (RECIST 1.1). The best overall radiologic response is the best response recorded from the start of the treatment until disease progression/recurrence (taking, as reference for progressive disease, the smallest measurements recorded since the treatment started). The subject's best response assignment depended on the achievement of both measurement and confirmation criteria. | 24 weeks |