A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With or Without Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-Resistant Prostate Cancer and Other Tumors Associated With PSMA Expression
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 345
- 试验地点
- 35
- 主要终点
- Incidence and severity of Serious Adverse Events (SAEs)
研究概览
简要总结
The main purpose of this study is to determine the safety, tolerability (how the body reacts to the drug[s]) and effectiveness (ability to treat the cancer) of REGN5678 (Nezastomig) alone, or in combination with cemiplimab.
The study has 2 parts. The goal of Part 1 (dose escalation) is to determine a safe dose(s) of REGN5678 when it is given alone or in combination with cemiplimab. The goal of Part 2 (dose expansion) is to use the REGN5678 drug dose(s) found in Part 1 to see how well REGN5678 alone or in combination with cemiplimab works to shrink tumors.
This study is looking at several other research questions, including:
- Side effects that may be experienced by taking REGN5678 alone or in combination with cemiplimab
- How REGN5678 alone or in combination with cemiplimab works in the body
- How much REGN5678 and/or cemiplimab are present in the blood
- To see if REGN5678 alone or in combination with cemiplimab works to reduce the size of the tumor by helping the immune system destroy the tumor
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
- All
- 接受健康志愿者
- 否
入选标准
- •mCRPC cohorts (men):
- •Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma.
- •PSA value at screening ≥4 ng/mL that has progressed within 6 months prior to screening as defined in the protocol.
- •Has received ≥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 (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)
- •177Lu-PSMA-617 radiotherapy, or another lutetium-based PSMA targeted radioligand, as described in the protocol
- •ccRCC cohorts (men and women):
- •Histologically or cytologically confirmed RCC with a clear-cell component.
- •Diagnosis of metastatic ccRCC with at least one measurable lesion via RECIST 1.1 criteria
- •Has progressed on or after ≥1 line prior systemic therapy approved in the metastatic setting. Prior treatment must include an anti-Programmed Death-1 (receptor) [PD-1]/Programmed Death-Ligand 1 (PD-L1) therapy and either ipilimumab and/or a tyrosine kinase inhibitor
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, as described in the protocol
- •Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy, as described in the protocol
- •Has received prior PSMA-targeting therapy with the exception of a PSMA targeting radioligand (eg. 177Lu-PSMA-617) in mCRPC
- •Dose Escalation: Has had prior anti-cancer immunotherapy (other than sipuleucel-T) within 5 half-lives prior to study therapy.
- •Dose Expansion (mCRPC only): Has had prior anti-cancer immunotherapy, as described in the protocol
- •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, as described in the protocol
- •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
- •NOTE: Other protocol defined Inclusion/Exclusion Criteria apply
研究组 & 干预措施
ccRCC - dose expansion cohort
REGN5678 with or without cemiplimab
干预措施: REGN5678 (Drug)
mCRPC - dose expansion cohort
REGN5678 with or without cemiplimab
干预措施: REGN5678 (Drug)
ccRCC - dose escalation cohort
REGN5678 with or without cemiplimab
干预措施: Cemiplimab (Drug)
ccRCC - dose escalation cohort
REGN5678 with or without cemiplimab
干预措施: REGN5678 (Drug)
mCRPC - dose escalation cohort
REGN5678 with or without cemiplimab
干预措施: REGN5678 (Drug)
mCRPC - dose escalation cohort
REGN5678 with or without cemiplimab
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Incidence and severity of Serious Adverse Events (SAEs)
时间窗: Through study completion, up to 5 years
Dose Escalation Phase
Number of participants with Grade ≥3 laboratory abnormalities
时间窗: Through study completion, up to 5 years
Dose Escalation Phase
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: First dose through day 42 of last participant in each dose level
Dose Escalation Phase
Concentration of REGN5678 in serum over time
时间窗: Through study completion, up to 5 years
Dose Escalation Phase
Concentration of REGN5678 in combination with cemiplimab in serum over time
时间窗: Through study completion, up to 5 years
Dose Escalation Phase
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Through study completion, up to 5 years
Dose Escalation Phase
Incidence and severity of Adverse Event of Special Interests (AESIs)
时间窗: Through study completion, up to 5 years
Dose Escalation Phase
Composite Response Rate (CRR) of 50% decline of Prostate Specific Antigen (PSA) and/or confirmed radiographic response of complete (CR) or partial response (PR)
时间窗: Through study completion, up to 5 years
Dose Expansion Phase - mCRPC cohort
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
时间窗: Through study completion, up to 5 years
Dose Expansion Phase - ccRCC cohort
次要结局
- CRR of 50% decline of PSA and/or confirmed radiographic of CR or PR(Through study completion, up to 5 years)
- ORR per RECIST 1.1 criteria(Through study completion, up to 5 years)
- Incidence and severity of TEAEs(Through study completion, up to 5 years)
- Incidence and severity of AESIs(Through study completion, up to 5 years)
- Incidence and severity of SAEs(Through study completion, up to 5 years)
- Number of participants with grade ≥3 laboratory abnormalities(Through study completion, up to 5 years)
- Concentration of REGN5678 in serum over time(Through study completion, up to 5 years)
- Concentration of REGN5678 in combination with cemiplimab in serum over time(Through study completion, up to 5 years)
- Percentage of participants with ≥50% decline of PSA(Through study completion, up to 5 years)
- Percentage of participants with ≥90% decline of PSA(Through study completion, up to 5 years)
- Presence or absence of antibodies against REGN5678(Through study completion, up to 5 years)
- Presence or absence of antibodies against cemiplimab(Through study completion, up to 5 years)