A Phase 2, Open-label, Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- MacroGenics
- 入组人数
- 192
- 试验地点
- 63
- 主要终点
- Part 1: Six-month Radiographic Progression Free Survival (rPFS) as Determined by the Investigator
研究概览
简要总结
Study CP-MGC018-03 is an open-label, two-part, Phase 2 study. Part 1 of 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 docetaxel-containing regimen, but no other chemotherapy agents.
This part of the study will assess the efficacy and tolerability of vobramitamab duocarmazine (MGC018) in two experimental arms (2.0 mg/kg every 4 weeks [Q4W] and 2.7 mg/kg Q4W) . Approximately 100 participants will be randomized 1:1.
Part 2 of the study will enroll participants with locally advanced or metastatic solid tumors. Participants must have progressive following at least 1 prior line of standard chemotherapy for advanced or metastatic disease. Participants will receive vobramitamab duocarmazine at a dose of 2.7 mg/kg every 4 weeks. Up to 200 participants may be enrolled in Part 2.
In both parts, vobramitamab duocarmazine will be administered intravenously (IV) in clinic on Day 1 of each 4-week cycle. Vobramitamab duocarmazine will be administered 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part 1 only: Histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine differentiation, signet cell, or small cell features.
- •Part 2 only: Histologically confirmed SCC or the anus, melanoma, HNSCC, squamous NSCLC, or SCLC.
- •Part 1 only: 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. Up to 3 total prior lines of therapy for mCRPC are permitted..
- •Part 2 only: At least 1 prior line of systemic therapy for unresectable or metastatic disease and no more than 2 prior lines of cytotoxic chemotherapy. Participants with HNSCC or melanoma must have received prior PD-1 or PD-L1 inhibitor for advanced or metastatic disease.
- •All participants must have ≥ 1 metastatic lesion, according to RECIST 1.1 or PCWG3 criteria, that is present on magnetic resonance imaging (MRI), computed tomography (CT), or bone scan obtained ≤ 28 days prior to initiation of study treatment.
- •All participants must have tumor progression, according to disease-specific criteria, following their most recent anti-cancer therapy.
- •All participants must have and available archival or formalin-fixed paraffin-embedded (FFPE) tumor tissue sample for participants with metastasis to internal organs
- •All participants have acceptable physical condition and laboratory values.
- •All participants of childbearing potential must agree to use highly effective methods of birth control.
- •All participants must not be pregnant, planning to be pregnant, or breastfeeding.
排除标准
- •Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.
- •Part 1 only: Received >1 prior taxane-containing regimen for prostate cancer. A second taxane regimen of <60 days used as bridging for lutetium-177 is permitted.
- •Part 1 only: Received >3 total prior therapies for mCRPC
- •Part 1 only: 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.
- •Part 1 only: Use of products that have published anti-prostate cancer activity or are known to decrease PSA.
研究组 & 干预措施
Part 1: MGC018 2.7 mg (Arm B)
MGC018 2.7 mg/kg every 4 weeks
干预措施: vobramitamab duocarmazine 2.7 mg (Arm B) (Biological)
Part 1: MGC018 2.0 mg (Arm A)
MGC018 2.0 mg/kg every 4 weeks
干预措施: vobramitamab duocarmazine 2.0 mg (Arm A) (Biological)
Part 2
MGC018 2.7 mg/kg every 4 weeks
干预措施: vobramitamab duocarmazine (Biological)
Part 1: Control Arm
Patients are administered abiraterone or enzalutamide
干预措施: Abiraterone (Drug)
Part 1: Control Arm
Patients are administered abiraterone or enzalutamide
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Part 1: Six-month Radiographic Progression Free Survival (rPFS) as Determined by the Investigator
时间窗: Assessed every 8 weeks for six months. Six month data reported.
The landmark analysis for 6 month rPFS rate will occur when all participants on Part 1 have been on study for at least 6 months.
Part 2: Objective Response Rate (ORR) Per Investigator Assessment of Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 Criteria
时间窗: Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months.
The ORR is defined as the percentage of participants in the response evaluable population who achieve a best overall response of complete response (CR) or partial response (PR), per RECIST version 1.1 criterial CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease from baseline in the sum of diameters of target lesions.
次要结局
- Part 1: ORR Per PCWG3 Criteria as Determined by the Investigator(Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months,)
- Part 1: Median Duration of Response (DoR) Per PCWG3 Criteria as Determined by the Investigator(Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months.)
- Part 1: Mean Best Tumor Size Change Over Time(Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months.)
- Part 1: Prostate-specific Cancer Antigen (PSA) Response Rate Per PCWG3 Criteria(Every 4 weeks throughout study participation. Average duration 10 months.)
- Part 1: Time to PSA Progression Per PCWG3 Criteria(Every 4 weeks throughout study participation. Average duration of participation, 10 months.)
- Part 1: Duration of PSA Response Per PCWG3 Criteria(Every 4 weeks throughout study participation. Average duration of participation, 10 months.)
- Part 1: Best PSA Percent Change(Every 4 weeks throughout study participation. Average duration of participation, 10 months.)
- Part 1: Time to First Symptomatic Skeletal Event (SSE)(Every 4 weeks throughout the study. Average duration of participation, 10 months.)
- Number of Participants With Adverse Event (AEs), Serious AEs (SAEs), and AEs Leading to Study Treatment Discontinuation.(Throughout the study, average duration of participation, 10 months.)
- Number of Participants Who Develop Anti-drug Antibodies (ADA)(Every 4 weeks throughout the study, average duration of participation was 10 months.)
- Part 2: Median DoR Per Investigator Assessment of RECIST 1.1 Criteria(Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months.)
- Part 2: Median Progression Free Survival (PFS) Per Investigator Assessment of RECIST 1.1 Criteria(Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months.)