A Study of Two Dose Levels of Vobramitamab Duocarmazine in Participants With Metastatic Castration Resistant Prostate Cancer

Study Overview
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Brief Summary
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Study CP-MGC018-03 is a randomized, open-label, Phase 2 study. The study will enroll participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one prior androgen receptor axis-targeted therapy (ARAT). ARAT includes abiraterone, enzalutamide, or apalutamide. Participants may have received up to 1 prior taxane-containing regimen, but no other chemotherapy agents. The study will assess efficacy and tolerability of two vobramitamab duocarmazine (MGC018) experimental arms (2.0 mg/kg every 4 weeks [Q4W] and 2.7 mg/kg Q4W) . Approximately 100 participants will be randomized 1:1. Vobramitamab duocarmazine will be administered intravenously (IV) in clinic on Day 1 of each 4-week cycle. Vobramitamab duocarmazine will be administered for up to 26 cycles, approximately 2 years, until criteria for treatment discontinuation are met. Participants will undergo regular testing for signs of disease progression using computed tomography (CT) scans, magnetic resonance imaging (MRI), bone scans, and prostate-specific antigen (PSA) blood tests. Routine examinations and blood tests will be performed and evaluated by the study doctor. An analysis of radiographic progression-free survival (rPFS) will occur after 100 participants have been on-study for at least 6 months.

Official Title
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A Phase 2, Randomized, Open-label, Study of Two Dose Levels of Vobramitamab Duocarmazine in Participants With Metastatic Castration-resistant Prostate Cancer

Conditions
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Castration-Resistant Prostatic Cancer, Androgen-Independent Prostatic Cancer, Hormone Refractory Prostatic Cancer, Androgen-Insensitive Prostatic Cancer, Androgen-Resistant Prostatic Cancer

Intervention / Treatment
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* Biological: vobramitamab duocarmazine 2.0 mg (Arm A)
* Biological: vobramitamab duocarmazine 2.7 mg (Arm B)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine differentiation, signet cell, or small cell features. Participants must have ≥ 1 metastatic lesion that is present on magnetic resonance imaging (MRI), computed tomography (CT), or bone scan obtained ≤ 28 days prior to initiation of study treatment. Tumor progression at study entry documented by PSA or imaging per PCWG3 criteria Received 1 prior ARAT for metastatic or non-metastatic, castration-sensitive or castration-resistant prostate cancer. A second ARAT regimen of <60 days used as bridging to lutetium-177 is permitted. Availability of archival or formalin-fixed paraffin-embedded (FFPE) tumor tissue sample for participants with metastasis to internal organs Acceptable physical condition and laboratory values. Exclusion Criteria: Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures. Received >1 prior taxane-containing regimen for prostate cancer. A second taxane regimen of <60 days used as bridging for lutetium-177 is permitted. Received >3 total prior therapies for mCRPC Participants with known BRCA or ATM mutation (germline or somatic) are not eligible unless they received prior treatment with a PARP inhibitor where available, indicated and tolerated. Another hematologic or solid tumor ≥ stage 1 malignancy that completed surgery, last dose of radiotherapy, or last dose of systemic anti-cancer therapy ≤ 2 years from first dose of study treatment. Participants who had curative therapy for non-melanomatous skin cancer or for localized malignancy are eligible. Untreated, symptomatic central nervous system (CNS) metastasis. Prior treatment with any B7-H3 targeted agent for cancer, Contradictions to the use of corticosteroid treatment Prior stem cell, tissue, or solid organ transplant. Use of products that have published anti-prostate cancer activity or are known to decrease PSA.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MGC018 2.0 mg (Arm A)<br>MGC018 2.0 mg/kg every 4 weeks | Biological: vobramitamab duocarmazine 2.0 mg (Arm A)<br>* 2.0 mg/kg intravenous (IV) every 4 weeks<br>* Other names: MGC018;|
| Experimental: MGC018 2.7 mg (Arm B)<br>MGC018 2.7 mg/kg every 4 weeks | Biological: vobramitamab duocarmazine 2.7 mg (Arm B)<br>* 2.7 mg.kg IV every 4 weeks<br>* Other names: MGC018;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic progression free survival (rPFS) as determined by the investigator | The rPFS is defined as the time from the date of randomization to the date of first documented progressive disease (PD) per Prostate Cancer Working Group 3 (PCWG3) or death from any cause, whichever occurs first. Three arms will be compared: Arm A, Arm B, and control. | Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) by PCWG3 criteria using investigator review | The number of participants experiencing a complete response (CR) or partial response (PR) to treatment. | Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years | 
| Duration of response (DoR) per PCWG3 criteria using investigator review | The DoR will be calculated as the time from the date of initial tumor response (CR or PR) to the date of first documented PD or death from any cause, whichever occurs first. | Every 8 weeks throughout study participation, up to 2 years | 
| Prostate-specific Cancer Antigen (PSA) response rate per PCWG3 criteria | PSA response is defined as a ≥ 50% decline in PSA from baseline with PSA confirmation ≥ 3 weeks after the first documented reduction in PSA of ≥ 50%. | Every 4 weeks throughout study participation, up to 2 years | 
| Time to PSA progression per PCWG3 criteria | In participants with a decrease in PSA from baseline: ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir value, which is confirmed by a consecutive second value obtained ≥ 3 weeks later. In participants with no decrease in PSA from baseline: ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline value after 12 weeks. | Every 4 weeks throughout study participation, up to 2 years | 
| Duration of PSA response per PCWG3 criteria | Duration of PSA response is defined as the time from the date of first documented PSA response to the earliest date of PSA progression. | Every 4 weeks throughout study participation, up to 2 years | 
| PSA percent change over time |  | Every 4 weeks throughout study participation, up to 2 years | 
| Best PSA percent change |  | Every 4 weeks throughout study participation, up to 2 years | 
| Time to first symptomatic skeletal event (SSE) | An SSE is defined as any of the following events: new symptomatic pathological fracture, requirement for radiation therapy to relieve bone pain, spinal cord compression, or tumor-related orthopedic surgical intervention. The time to first SSE is defined as the time from the date of randomization to the first occurrence of SSE. | Every 4 weeks throughout the study, up to 2 years | 
| Number of participants with adverse event (AEs), serious AEs (SAEs), and AEs leading to study treatment discontinuation. |  | Throughout the study, up to 2 years | 
| Number of participants who develop anti-drug antibodies |  | Throughout the study, up to 2 years | 
| maximum concentration or concentration at the end of infusion (Cmax) | The highest measured concentration of vobramitamab duocarmazine in the bloodstream. | Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, 6-8 hours after EOI, and Cycle 1 Day 15. Pre-infusion and EOI on Cycle 2 Days 1, Cycle 2 Day 15; Pre-infusion and EOI on Day 1 of Cycles 3, 4, 5, 6, 9 and 12 (28-day cycle) | 
| area under the concentration time curve (AUC) | AUC is the total amount of vobramitamab duocarmazine in bloodstream after drug administration | Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, 6-8 hours after EOI, and Cycle 1 Day 15. Pre-infusion and EOI on Cycle 2 Days 1, Cycle 2 Day 15; Pre-infusion and EOI on Day 1 of Cycles 3, 4, 5, 6, 9 and 12 (28-day cycle) | 
| Trough drug concentration (Ctrough or Cmin) | Trough concentration is the concentration measured before a subsequent dose of vobramitamab duocarmazine | Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, 6-8 hours after EOI, and Cycle 1 Day 15. Pre-infusion and EOI on Cycle 2 Days 1, Cycle 2 Day 15; Pre-infusion and EOI on Day 1 of Cycles 3, 4, 5, 6, 9 and 12 (28-day cycle) | 
| Clearance (CL) | Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time | Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, 6-8 hours after EOI, and Cycle 1 Day 15. Pre-infusion and EOI on Cycle 2 Days 1, Cycle 2 Day 15; Pre-infusion and EOI on Day 1 of Cycles 3, 4, 5, 6, 9 and 12 (28-day cycle) | 
| Volume of distribution (Vz) | The volume of distribution is related to how much drug is distributed to body tissues, or remains in the bloodstream. | Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, 6-8 hours after EOI, and Cycle 1 Day 15. Pre-infusion and EOI on Cycle 2 Days 1, Cycle 2 Day 15; Pre-infusion and EOI on Day 1 of Cycles 3, 4, 5, 6, 9 and 12 (28-day cycle) | 
| Terminal half-life | Terminal elimination half-life is the time it takes for the concentration of the drug in plasma or serum to be reduced by 50% | Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, 6-8 hours after EOI, and Cycle 1 Day 15. Pre-infusion and EOI on Cycle 2 Days 1, Cycle 2 Day 15; Pre-infusion and EOI on Day 1 of Cycles 3, 4, 5, 6, 9 and 12 (28-day cycle) |