Phase 1/2 Study of REGN4336 (a PSMAxCD3 Bispecific Antibody) Administered Alone or in Combination With 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
- 228
- 试验地点
- 14
- 主要终点
- Incidence and severity of Serious Adverse Events (SAEs)
研究概览
简要总结
This study is researching an investigational drug called REGN4336 both alone or together with another investigational drug called REGN5678. The study is focused on participants with previously treated metastatic prostate cancer.
The main purpose of the study is to look at the safety, tolerability (how the body reacts to the drug) and effectiveness (how well the drug works to shrink tumors) of REGN4336 when given in combination with REGN5678.
The study has 2 parts. The purpose of Part 1 is to determine a safe dose(s) of REGN4336 to be given alone or in combination with REGN5678. Part 1 is known as the "dose escalation" phase.
The purpose of Part 2, (known as the "dose expansion" phase), is to use the doses of REGN4336 and REGN5678 selected in Part 1 to further test how well the combination treatment with REGN4336 and REGN5678 works to shrink tumors.
The study is looking at several other research questions, including:
- What side effects may happen from taking REGN4336 alone or in combination with REGN5678
- How well does REGN4336 in combination with REGN5678 reduce tumor size
- How much REGN4336 is in the blood at different times when it is given alone or in combination with REGN5678
- Does the body make antibodies against the study drugs (REGN4336 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 and that has progressed within 6 months prior to screening, according to at least 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 biologic therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities except for laboratory changes as described in inclusion criteria
- •Has received any previous systemic biologic or anti-cancer immunotherapy within 5 half-lives of first dose of study therapy, as described in the protocol
- •Has received prior Prostate-Specific Membrane Antigen (PSMA)-targeting therapy NOTE: Prior therapy with PSMA-targeting radioligand(s) (eg, 177Lu-PSMA-617) is permitted. However, a period of 12 weeks must elapse between the last dose of the PSMA- targeting radioligand and the first dose of study drug
- •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 Virus (HBV), or Hepatitis C Virus (HCV) 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
干预措施: REGN4336 (Drug)
Module 3-Combo Therapy
干预措施: REGN4336 (Drug)
Module 3-Combo Therapy
干预措施: REGN5678 (Drug)
结局指标
主要结局
Incidence and severity of Serious Adverse Events (SAEs)
时间窗: Up to 5 years
Dose escalation
REGN4336 monotherapy concentrations in serum
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: up to 21 days
Dose escalation
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to 5 years
Dose escalation
Incidence and severity of Adverse Events of Special Interest (AESIs)
时间窗: Up to 5 years
Dose escalation
Composite Response Rate (CRR) of ≥50% decline of prostate specific antigen (PSA) and/or confirmed radiographic response of complete response (CR) or partial response (PR)
时间窗: Up to 5 years
Dose expansion
次要结局
- ADA to REGN4336 and REGN5678(Up to 5 years)
- Incidence and severity of SAEs(Up to 5 years)
- REGN4336 concentrations in serum in combination with REGN5678(Up to 5 years)
- Incidence and severity of TEAEs(Up to 5 years)
- Incidence and severity of AESIs(Up to 5 years)
- Anti-Drug Antibodies (ADA) to REGN4336(Up to 5 years)
- CRR of ≥50% decline of PSA and/or confirmed radiographic response of CR or PR(Up to 5 years)
- Percentage of patients with ≥50% reduction in PSA confirmed by a second PSA test ≥3 weeks later(Up to 5 years)
- Percentage of patients with ≥90% reduction in PSA confirmed by a second PSA test ≥3 weeks later(UP to 5 years)