MGC018 Versus Androgen Receptor Axis-targeted Therapy in Participants With Metastatic Castration Resistant Prostate Cancer (Tamarack)

• ClinicalTrials.gov Identifier: NCT05551117
• Recruitment Status: Recruiting
• First Posted: September 22, 2022
• Last Update Posted: November 29, 2022
• Sponsor: MacroGenics
• Information provided by (Responsible Party): MacroGenics

Study Description

Brief Summary:

Study CP-MGC018-03 is a randomized, open-label, seamless, Phase 2/3 study. The study will enroll participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one prior androgen receptor axis-targeted therapy (ARAT) and one prior taxane-containing regimen. ARAT includes abiraterone, enzalutamide, or apalutamide. Participants may have received up to 1 prior cabazitaxel regimen, but no other chemotherapy agents.

The Phase 2 stage will assess efficacy and tolerability of two vobramitamab duocarmazine (MGC018) experimental arms (2.0 mg/kg Q4W and 2.7 mg/kg Q4W) compared to the control arm (abiraterone or enzalutamide). Approximately 150 participants will be randomized 1:1:1 in Phase 2 among the three study treatment arms (two vobramitamab duocarmazine experimental arms and one control arm). An interim analysis will be performed to select the Phase 3 dose regimen for the vobramitamab duocarmazine experimental arm for Phase 3 after approximately 150 participants enrolled in Phase 2 have been followed for at least 2 months (60 days).

The Phase 3 stage will assess efficacy of the selected dose regimen for the vobramitamab duocarmazine experimental arm versus the control arm (abiraterone or enzalutamide). Approximately 270 additional participants will be randomized 1:1 between each study treatment arm in Phase 3 (one vobramitamab duocarmazine experimental arm and the control arm).

Condition or disease	Intervention/treatment	Phase
Castration-Resistant Prostatic Cancer; Androgen-Independent Prostatic Cancer; Androgen-Insensitive Prostatic Cancer; Androgen-Resistant Prostatic Cancer; Hormone Refractory Prostatic Cancer	Drug: ARAT; Biological: vobramitamab duocarmazine 2.0 mg (Arm A); Biological: vobramitamab duocarmazine 2.7 mg (Arm B)	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 420 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2/3, Randomized, Open-label, Study of MGC018 Versus Androgen Receptor Axis-targeted Therapy (Abiraterone or Enzalutamide) in Participants With Metastatic Castration-resistant Prostate Cancer
• Estimated Study Start Date: November 2022
• Estimated Primary Completion Date: December 2026
• Estimated Study Completion Date: December 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Control Arm; ARAT: either abiraterone or enzalutamide	Drug: ARAT; androgen receptor axis-targeted therapy; Other Names: abiraterone; enzalutimide; Zytiga; Xtandi
Experimental: MGC018 2.0 mg (Arm A); MGC018 2.0 mg/kg every 4 weeks	Biological: vobramitamab duocarmazine 2.0 mg (Arm A); 2.0 mg/kg intravenous (IV) every 4 weeks; Other Name: MGC018
Experimental: MGC018 2.7 mg (Arm B); MGC018 2.7 mg/kg every 4 weeks	Biological: vobramitamab duocarmazine 2.7 mg (Arm B); 2.7 mg.kg IV every 4 weeks; Other Name: MGC018

Outcome Measures

Primary Outcome Measures :

1. Radiographic progression free survival (rPFS) using blinded independent central review (BICR) in Phase 2 [ Time Frame: Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years ]
   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.
2. rPFS) using BICR in Phase 3 [ Time Frame: Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years ]
   The rPFS is defined as the time from the date of randomization to the date of first documented PD per PCWG3 or death from any cause, whichever occurs first. Two arms will be compared: Arm A or Arm B, and control

Secondary Outcome Measures :

1. Prostate-specific Cancer Antigen (PSA) response rate per PCWG3 criteria in Phase 2 [ Time Frame: Every 4 weeks throughout study participation, up to 2 years ]
   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%.
2. Time to PSA progression per PCWG3 criteria In Phase 2 [ Time Frame: Every 4 weeks throughout study participation, up to 2 years ]

   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.

3. Overall response rate (ORR) in Phase 2 [ Time Frame: Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years ]
   The number of participants experiencing a complete response (CR) or partial response (PR) to treatment.
4. Duration of response (DoR) per PCWG3 criteria and BICR in Phase 2 [ Time Frame: Every 8 weeks throughout study participation, up to 2 years ]
   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.
5. ORR per PCWG3 in Phase 3 [ Time Frame: Every 8 weeks throughout study participation, up to 2 years ]
   The number of participants experiencing a CR or PR to treatment according to PCWG3 criteria using BICR. Three arms will be compared: Arm A, Arm B, and control.
6. DoR in Phase 3 [ Time Frame: Every 8 weeks throughout study participation, up to 2 years. ]
   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. Two arms will be compared: Arm A or Arm B, and control.
7. Disease Control Rate (DCR) in Phase 3 [ Time Frame: Every 8 weeks throughout study participation, up to 2 years. ]
   DCR is defined as the percentage of participants with a response of CR, PR, or SD for at least 3 months. Two arms will be compared: Arm A or Arm B, and control.
8. Overall survival (OS) in Phase 3 [ Time Frame: Every 12 weeks up to 4 years ]
   The time from the date of randomization to date of death from any cause.
9. rPFS per PCWG3 using investigator review [ Time Frame: Every 8 weeks throughout study participation, up to 2 years. ]
   The rPFS is defined as the time from the date of randomization to the date of first Investigator-documented PD per PCWG3 or death from any cause, whichever occurs first.
10. ORR per PCWG3 using investigator review [ Time Frame: Every 8 weeks throughout study participation, up to 2 years. ]
    The number of participants experiencing a complete response or partial response to treatment.
11. DoR per PCWG3 using investigator review [ Time Frame: Every 8 weeks throughout study participation, up to 2 years. ]
    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.
12. Duration of PSA response per PCWG3 criteria [ Time Frame: Every 4 weeks throughout study participation, up to 2 years ]
    Duration of PSA response is defined as the time from the date of first documented PSA response to the earliest date of PSA progression.
13. PSA percent change over time [ Time Frame: Every 4 weeks throughout study participation, up to 2 years ]
14. Best PSA percent change [ Time Frame: Every 4 weeks throughout study participation, up to 2 years ]
15. Time to pain progression based on BPI-sf worst pain severity in Phase 3 [ Time Frame: Every 4 weeks throughout study participation, up to 2 years ]
    Pain progression is defined as an increase of ≥ 30% from baseline in the BPI-sf worst pain intensity score (item 3) observed at 2 consecutive evaluations ≥ 4 weeks apart. Time to pain progression is defined as the time interval from randomization to the first date a participant experiences pain progression.
16. Number of participants with pain progression based on BPI-sf worst pain severity in Phase 3 [ Time Frame: Every 4 weeks throughout study participation, up to 2 years ]
    Pain progression is defined as an increase of ≥ 30% from baseline in the BPI-sf worst pain intensity score (item 3) observed at 2 consecutive evaluations ≥ 4 weeks apart.
17. Change from baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) score In Phase 3 [ Time Frame: Every 4 weeks throughout the study, up to 2 years ]
    Change from baseline of FACT-P total scale/subscale scores at each scheduled visit will be summarized by study treatment arm. The Functional Assessment of Cancer Therapy - Prostate (FACT-P) measures the health-related quality of life in men with prostate cancer. Individual statements regarding quality of life are scored from 0 to 4. Scores are tallied and the higher the score, the better the Quality of Life.
18. Mean values in Functional Assessment of Cancer Therapy - Prostate (FACT-P) score In Phase 3 [ Time Frame: Time Frame: Every 4 weeks throughout the study, up to 2 years ]
    Mean values of FACT-P total scale/subscale scores at each scheduled visit will be summarized by study treatment. The Functional Assessment of Cancer Therapy - Prostate (FACT-P) measures the health-related quality of life in men with prostate cancer. Individual statements regarding quality of life are scored from 0 to 4. Scores are tallied and the higher the score, the better the Quality of Life.
19. Time to first symptomatic skeletal event (SSE) in Phase 3 [ Time Frame: Every 4 weeks throughout the study, up to 2 years ]
    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.
20. Number of participants with adverse event (AEs), serious AEs (SAEs), and AEs leading to study treatment discontinuation. [ Time Frame: Throughout the study, up to 2 years ]
21. Number of participants who develop anti-drug antibodies [ Time Frame: Throughout the study, up to 2 years ]
22. maximum concentration or concentration at the end of infusion (Cmax) [ Time Frame: 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) ]
    The highest measured concentration of vobramitamab duocarmazine in the bloodstream.
23. area under the concentration time curve (AUC) [ Time Frame: 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) ]
    AUC is the total amount of vobramitamab duocarmazine in bloodstream after drug administration
24. Trough drug concentration (Ctrough or Cmin) [ Time Frame: 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 concentration is the concentration measured before a subsequent dose of vobramitamab duocarmazine
25. Clearance (CL) [ Time Frame: 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) ]
    Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time
26. Volume of distribution (Vz) [ Time Frame: 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) ]
    The volume of distribution is related to how much drug is distributed to body tissues, or remains in the bloodstream.
27. Terminal half-life [ Time Frame: 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 elimination half-life is the time it takes for the concentration of the drug in plasma or serum to be reduced by 50%

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

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 prostate cancer (mPC) with lack of progression for at least 12 months
• Received 1 prior taxane-containing regimen for mPC.
• May have received up to 1 prior cabazitaxel regiment for mPC.
• 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.
• Prior chemotherapy other than docetaxel or cabazitaxel. Prior immunotherapy and radiopharmaceutical therapy is allowed.
• Known history of documented BRCA or ATM mutation (germline or somatic). Participants with known BRCA or ATM mutation who had disease progression or unacceptable toxicity on a PARP inhibitor are eligible.
• 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.

Contacts and Locations

Contacts

Contact: Global Trial Manager; 301-251-5172; info@macrogenics.com

Locations

United States, Florida

Mid Florida Hematology and Oncology Center; Recruiting

Orange City, Florida, United States, 32763

Contact: Kiran Penta

Principal Investigator: Santosh Nair, MD

United States, Louisiana

Pontchartrain Cancer Center; Recruiting

Covington, Louisiana, United States, 70433

Contact: Jessica Faucheaux

Principal Investigator: David Oubre, MD

Sponsors and Collaborators

MacroGenics

Investigators

• Study Director: Stephen L Eck, M.D.; MacroGenics

More Information

• Responsible Party: MacroGenics
• ClinicalTrials.gov Identifier: NCT05551117
• Other Study ID Numbers: CP-MGC018-03
• First Posted: September 22, 2022
• Last Update Posted: November 29, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases