A Phase 2 Dose Optimization Trial Evaluating a CD46-Targeted Antibody-Drug Conjugate (FG-3246) in Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Kyntra Bio
- 入组人数
- 75
- 试验地点
- 23
- 主要终点
- Radiographic Progression-free Survival (rPFS) By Investigator Assessment Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria
研究概览
简要总结
The purpose of this study is to evaluate the safety, efficacy, tolerability, and pharmacokinetics (PK) of FG-3246, a cluster of differentiation 46 (CD46) targeting antibody-drug conjugate (ADC), in the treatment of participants with mCRPC who have progressed following treatment with one prior second-generation androgen receptor signaling inhibitor (ARSI) in any setting and no prior taxane therapy in the mCRPC setting.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Participant must have histological, and/or cytological confirmation of prostate adenocarcinoma on all prior tumor biopsies.
- •Participant with soft tissue disease and a safely accessible soft tissue tumor lesion(s) must agree to biopsy of a primary or metastatic lesion during screening. Alternatively, participant may provide a suitable archival biopsy of a primary or metastatic lesion.
- •Participant must have serum testosterone levels <50 nanograms (ng)/deciliter (dL) during screening.
- •Participant is required to have progressed on no more than one prior treatment with a second generation ARSI (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) initiated in either the castration-sensitive or castration-resistant setting.
- •Participant must have progressive mCRPC following last treatment at screening.
- •Participant must have ≥1 metastatic lesion that is present on baseline Computed Tomography (CT), Magnetic Resonance Imaging (MRI), or bone scan obtained ≤28 days prior to randomization.
- •Participant must have adequate organ function during screening.
排除标准
- •Participant has received previous treatment with a therapeutic targeting CD
- •Participant has small cell neuroendocrine carcinoma (pure or mixed) on any prior histologic evaluation of primary or metastatic lesion.
- •Participant has progressed on more than one prior second-generation ARSI in any setting or has received more than two prior second-generation ARSIs in any setting.
- •Participants must not have received recent anticancer treatments before enrollment. Ongoing supportive or hormonal therapies are allowed if they were started well before randomization and are continued without change.
- •Participant has received any prior radiation therapy within 14 days prior to randomization.
- •Participant has a known actionable mutation or gene alteration, for example, BRCA1 mutation, for which approved therapies are available, for example, PARP inhibitors, unless these therapies are not appropriate for the participant as determined by the investigator or the participant refuses such therapy.
- •Participant has National Cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 2 peripheral neuropathy at the time of screening from any etiology.
- •Participant has received any prior chemotherapy; however, one prior taxane-based chemotherapy in the castration-sensitive setting is allowed if completed >12 months before randomization.
- •Participant has known hypersensitivity to the components of FG-3246 or its analogs or a history of allergic or anaphylactic reaction to human, humanized, or chimeric monoclonal antibodies.
- •Participant has diagnosis with any other malignancy in the past 5 years, except for adequately treated basal cell or squamous cell carcinoma of the skin.
- •Participant requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer drug that cannot be safely discontinued.
- •NOTE: Other protocol-defined inclusion/exclusion may apply.
研究组 & 干预措施
FG-3246 1.8 mg/kg
Participants will receive FG-3246 1.8 milligrams (mg)/kilogram (kg) administered via intravenous (IV) infusion on Day 1 of each 21-day treatment cycle (every 3 weeks [Q3W]) until radiographic progression, unacceptable safety and tolerability, participant or investigator decision to stop treatment, other withdrawal criteria are met, or sponsor decision to close the study.
干预措施: FG-3246 (Drug)
FG-3246 2.7 mg/kg
Participants will receive FG-3246 2.7 mg/kg administered via IV infusion on Day 1 of each 21-day treatment cycle (Q3W) until radiographic progression, unacceptable safety and tolerability, participant or investigator decision to stop treatment, other withdrawal criteria are met, or sponsor decision to close the study.
干预措施: FG-3246 (Drug)
FG-3246 2.4 mg/kg
Participants will receive FG-3246 2.4 mg/kg administered via IV infusion on Day 1 of each 21-day treatment cycle (Q3W) until radiographic progression, unacceptable safety and tolerability, participant or investigator decision to stop treatment, other withdrawal criteria are met, or sponsor decision to close the study.
干预措施: FG-3246 (Drug)
结局指标
主要结局
Radiographic Progression-free Survival (rPFS) By Investigator Assessment Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria
时间窗: Until radiographic progression is noted (up to approximately 30 months)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From first dose until 28 days after last dose (up to approximately 30 months)
Maximum Plasma Concentration (Cmax) of FG-3246, Total Anticluster of Differentiation 46 Antibody (CD46), and Free Monomethyl Auristatin E (MMAE)
时间窗: Within each 21 day treatment cycle from Cycle 1 through 28 days post last dose (up to approximately 30 months)
次要结局
- rPFS Rate at 6 Months (rPFS6) Per RECIST v1.1 and PCWG3 Criteria(Month 6)
- rPFS Rate at 12 Months (rPFS12) Per RECIST v1.1 and PCWG3 Criteria(Month 12)
- Confirmed Objective Response Rate (ORR) Per RECIST v1.1 and PCWG3 Criteria(From first dose up to approximately 30 months)
- Duration of Response (DoR) Per RECIST v1.1 and PCWG3 Criteria(From first dose up to approximately 30 months)
- Confirmed PSA50 Response Rate: Percentage of Participants Achieving a Decline in Prostate-specific Antigen (PSA) ≥50% From Baseline(Up to approximately 30 months)
- Confirmed PSA90 Response Rate: Percentage of Participants Achieving a Decline in PSA ≥90% From Baseline(Up to approximately 30 months)
- Composite Response Rate (CRR) Per RECIST 1.1 and PCWG3 Criteria(Up to approximately 30 months)
- PSA Progression-free Survival (PFS)(Up to approximately 30 months)
- Disease Control Rate (DCR) per RECIST 1.1 and PCWG3 Criteria(Up to approximately 30 months)
- Clinical Benefit Rate (CBR) per RECIST 1.1 and PCWG3 Criteria(Up to approximately 30 months)
- Time to First Symptomatic Skeletal-related Event (SSRE)(Up to approximately 30 months)
- Overall Survival (OS)(Until death or up to approximately 30 months)
- Percentage of Participants Who Develop Antidrug Antibodies (ADA) and Neutralizing Antibody (NAb) Against FG-3246(Within each 21 day treatment cycle from Cycle 1 through 28 days post last dose (up to approximately 30 months))