Phase 1/2 Study of REGN4336 (a PSMAxCD3 Bispecific Antibody) Administered Alone or in Combination With Cemiplimab or REGN5678 (a PSMAxCD28 Bispecific Antibody) in Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 370
- 试验地点
- 26
- 主要终点
- REGN4336 concentrations in serum in combination with cemiplimab
研究概览
简要总结
This study is researching an investigational drug called REGN4336. Some participants may receive additional investigational drugs in combination with REGN4336. These additional drugs include REGN5678, cemiplimab and sarilumab.
The main purpose of this study is to determine the safety, tolerability (how the body reacts to the drug) and effectiveness of REGN4336 alone, in combination with cemiplimab, or in combination with REGN5678. REGN4336, cemiplimab and REGN5678 are a type of treatment for cancer called immunotherapy,and are intended to activate T-cells to attack cancer cells.
This study has 2 parts. The purpose of Part 1 is to determine a safe dose of REGN4336 when given alone or when given in combination with cemiplimab or REGN5678. The purpose of Part 2 is to use the REGN4336 dose(s) determined in Part 1 to further test how well REGN4336 works to shrink tumors either when given alone or in combination with cemiplimab or REGN5678.
This study is looking at several other research questions, including:
- What side effects may happen from taking REGN4336 alone, in combination with cemiplimab, or in combination with REGN5678?
- How much REGN4336 is in the blood at different times when it is given alone, in combination with cemiplimab, or in combination with REGN5678?
- Does the body make antibodies against the study drugs (REGN4336, cemiplimab, or REGN5678)?
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma
- •Metastatic, castration-resistant prostate cancer (mCRPC) with PSA value at screening ≥4 ng/mL that has progressed within 6 months prior to screening, according to 1 of the following:
- •PSA progression as defined by a rising PSA level confirmed with an interval of ≥1 week between each assessment
- •Radiographic disease progression in soft tissue based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria with or without PSA progression
- •Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression NOTE: Measurable disease per RECIST version 1.1 per local reading at screening is not an eligibility criterion for enrollment
- •Has progressed upon or intolerant to ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to androgen deprivation therapy [ADT]) including at least one second-generation anti-androgen therapy (e.g. abiraterone, enzalutamide, apalutamide, or darolutamide)
排除标准
- •Has received treatment with an approved systemic therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities
- •Has received any previous systemic biologic or immune-modulating therapy (except for Sipuleucel-T) within 5 half-lives of first dose of study therapy, as described in the protocol
- •Has received prior PSMA-targeting therapy. Exception: Prior therapy with approved PSMA-targeted radioligand(s) is permitted
- •Any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study therapy
- •Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
- •Encephalitis, meningitis, neurodegenerative disease (with the exception of mild dementia that does not interfere with activities of daily living [ADLs]) or uncontrolled seizures in the year prior to first dose of study therapy
- •Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency, as described in the protocol.
- •NOTE: Other protocol defined Inclusion/Exclusion Criteria apply
研究组 & 干预措施
Module 1- Monotherapy
REGN4336
干预措施: REGN4336 (Drug)
Module 1- Monotherapy
REGN4336
干预措施: Sarilumab (Drug)
Module 2-Combo Therapy
REGN4336 + Cemiplimab
干预措施: REGN4336 (Drug)
Module 2-Combo Therapy
REGN4336 + Cemiplimab
干预措施: Cemiplimab (Drug)
Module 2-Combo Therapy
REGN4336 + Cemiplimab
干预措施: Sarilumab (Drug)
Module 3-Combo Therapy
REGN4336 + REGN5678
干预措施: REGN4336 (Drug)
Module 3-Combo Therapy
REGN4336 + REGN5678
干预措施: REGN5678 (Drug)
Module 3-Combo Therapy
REGN4336 + REGN5678
干预措施: Sarilumab (Drug)
结局指标
主要结局
REGN4336 concentrations in serum in combination with cemiplimab
时间窗: Up to 5 years
Dose escalation
Incidence and severity of Immune-mediated Adverse Events (imAEs)
时间窗: Up to 5 years
Dose escalation
Incidence and severity of Serious Adverse Events (SAEs)
时间窗: Up to 5 years
Dose escalation
Incidence and severity of adverse event of special interest (AESIs)
时间窗: Up to 5 years
Dose escalation
Number of patients with grade ≥3 laboratory abnormalities
时间窗: Up to 5 years
Dose escalation
REGN4336 concentrations in serum in combination with REGN5678
时间窗: Up to 5 years
Dose escalation
Incidence of dose-limiting toxicities (DLTs)
时间窗: 28 days, up to 42 days
Dose escalation
Incidence and severity of treatment-emergent adverse events (TEAEs)
时间窗: Up to 5 years
Dose escalation
REGN4336 monotherapy concentrations in serum
时间窗: Up to 5 years
Dose escalation
Objective response rate (ORR) per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria
时间窗: Up to 5 years
Dose expansion
次要结局
- ORR per modified per modified PCWG3 criteria(Up to 5 years)
- Incidence and severity of imAEs(Up to 5 years)
- Incidence and severity of SAEs(Up to 5 years)
- REGN4336 concentrations in serum in combination with cemiplimab(Up to 5 years)
- REGN4336 concentrations in serum in combination with REGN5678(Up to 5 years)
- Percentage of patients with ≥50% reduction in prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥3 weeks later(Up to 5 years)
- Incidence and severity of TEAEs(Up to 5 years)
- Incidence and severity of AESIs(Up to 5 years)
- REGN4336 monotherapy concentrations in serum(Up to 5 years)
- ADA to REGN4336 and cemiplimab(Up to 5 years)
- Percentage of patients with ≥90% reduction in PSA from baseline, confirmed by a second PSA test ≥3 weeks later(UP to 5 years)
- Anti-drug antibodies (ADA) to REGN4336(Up to 5 years)
- Number of patients with grade ≥3 laboratory abnormalities(Up to 5 years)
- ADA to REGN4336 and REGN5678(Up to 5 years)