A Phase 1/2 Study of REGN7075 (EGFRxCD28 Costimulatory Bispecific Antibody) in Combination With Cemiplimab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 548
- 试验地点
- 98
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This study is researching an investigational drug called marlotamig (REGN7075) by itself and in combination with cemiplimab with or without chemotherapy. The study is focused on patients with certain solid tumors that are in an advanced stage.
The aim of the study is to see how safe and tolerable marlotamig is by itself and in combination with cemiplimab (with or without chemotherapy), and to find out what is the best dose of marlotamig to be given to patients with advanced solid tumors when combined with cemiplimab (with or without chemotherapy). Another aim of the study is to see how effective marlotamig by itself, or in combination with cemiplimab (with or without chemotherapy), is at treating cancer patients.
The study is also looking at:
- Side effects that may be experienced by people taking marlotamig by itself and in combination with cemiplimab with or without chemotherapy
- How marlotamig works in the body by itself and in combination with cemiplimab with or without chemotherapy
- How much marlotamig is present in the blood when given by itself and in combination with cemiplimab with or without chemotherapy
- To see if marlotamig by itself and in combination with cemiplimab with or without chemotherapy works to treat cancer by controlling the proliferation of tumor cells to shrink the tumor
- Whether the body makes antibodies against the study drugs (marlotamig and cemiplimab) (which could make the drug less effective or could lead to side effects)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Has histologically or cytologically confirmed cancer that meets criteria as defined in the protocol
- •Expansion Cohorts only: Is anti-Programmed cell Death protein-1 (PD-1)/Programmed cell Death Ligand-1 (PD-L1) naïve, defined as never having previously been treated with a drug that targets the PD-1
- •Has at least 1 lesion that meets study criteria as defined in the protocol
- •Willing to provide tumor tissue from newly obtained biopsy (at a minimum core biopsy) from a tumor site that has not been previously irradiated
- •Has adequate organ and bone marrow function as defined in the protocol
- •In the judgement of the investigator, has a life expectancy of at least 3 months
排除标准
- •Is currently participating in another study of a therapeutic agent
- •Has participated in any study of an investigational agent or an investigational device within 4 weeks of the first administration of study drug as defined in the protocol
- •Has received treatment with an approved systemic therapy within 4 weeks of the first administration of study drug or has not yet recovered (ie, grade 1 or baseline) from any acute toxicities
- •Has received recent anti-Epidermal Growth Factor Receptor (EGFR) antibody therapy as defined in the protocol
- •Has received radiation therapy or major surgery within 14 days of the first administration of study drug or has not recovered (ie, grade 1 or baseline) from adverse events
- •Has received any previous systemic, non-immunomodulatory biologic therapy within 4 weeks of first administration of study drug.
- •Has had prior anti-cancer immunotherapy within 5 half-lives prior to study drug as defined in the protocol
- •Has second malignancy that is progressing or requires active treatment as defined in the protocol
- •Has any condition requiring ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1-2 weeks prior to the first dose of study drug as defined in the protocol
- •Has ongoing or recent (within 5 years) evidence of significant autoimmune disease or any other condition that required treatment with systemic immunosuppressive treatments as defined in the protocol
- •Has untreated or active primary brain tumor, Central Nervous System (CNS) metastases, leptomeningeal disease, or spinal cord compression
- •Has encephalitis, meningitis, organic brain disease (eg, Parkinson's disease) or uncontrolled seizures within 1 year prior to the first dose of study drug
- •Has any ongoing inflammatory skin disease as defined in the protocol
- •NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply
研究组 & 干预措施
Dose Expansion C
Non-Small Cell Lung Cancer (NSCLC)
干预措施: Platinum-based doublet chemotherapy (Drug)
Dose Escalation
Variety of mixed advanced solid tumor types
干预措施: Cemiplimab (Drug)
Dose Expansion E
Microsatellite Stable-Colorectal Cancer (MSS-CRC), with Active Liver Metastases and/or Active Peritoneal Metastases
干预措施: Cemiplimab (Drug)
Dose Expansion I
Third-line (3L) MSS-CRC with Active Liver Metastases
干预措施: Trifluridine-tipiracil (Drug)
Dose Expansion J
3L MSS-CRC without Active Liver Metastases
干预措施: Trifluridine-tipiracil (Drug)
Dose Expansion I
Third-line (3L) MSS-CRC with Active Liver Metastases
干预措施: REGN7075 (Drug)
Dose Expansion I
Third-line (3L) MSS-CRC with Active Liver Metastases
干预措施: Bevacizumab (Drug)
Dose Expansion G
Epidermal Growth Factor Receptor (EGFR) -mutant NSCLC Post Third Generation tyrosine kinase inhibitor (TKI)
干预措施: Platinum-based doublet chemotherapy (Drug)
Dose Expansion J
3L MSS-CRC without Active Liver Metastases
干预措施: Cemiplimab (Drug)
Dose Expansion H
EGFR-mutant NSCLC Post Third Generation TKI and Post Platinum-Doublet Chemotherapy
干预措施: Cemiplimab (Drug)
Dose Expansion H
EGFR-mutant NSCLC Post Third Generation TKI and Post Platinum-Doublet Chemotherapy
干预措施: REGN7075 (Drug)
Dose Expansion B
Cutaneous Squamous Cell Carcinoma (CSCC)
干预措施: Cemiplimab (Drug)
Dose Expansion C
Non-Small Cell Lung Cancer (NSCLC)
干预措施: Cemiplimab (Drug)
Dose Expansion F
MSS-CRC with Isolated Lung/Lymph Node Metastases (no active liver and no active peritoneal metastases)
干预措施: Cemiplimab (Drug)
Dose Expansion I
Third-line (3L) MSS-CRC with Active Liver Metastases
干预措施: Cemiplimab (Drug)
Dose Expansion J
3L MSS-CRC without Active Liver Metastases
干预措施: REGN7075 (Drug)
Dose Expansion J
3L MSS-CRC without Active Liver Metastases
干预措施: Bevacizumab (Drug)
Dose Expansion D
Head and Neck Squamous Cell Carcinoma (HNSCC)
干预措施: Cemiplimab (Drug)
Dose Expansion A
Triple Negative Breast Cancer (TNBC)
干预措施: REGN7075 (Drug)
Dose Expansion F
MSS-CRC with Isolated Lung/Lymph Node Metastases (no active liver and no active peritoneal metastases)
干预措施: REGN7075 (Drug)
Dose Expansion G
Epidermal Growth Factor Receptor (EGFR) -mutant NSCLC Post Third Generation tyrosine kinase inhibitor (TKI)
干预措施: Cemiplimab (Drug)
Dose Escalation
Variety of mixed advanced solid tumor types
干预措施: REGN7075 (Drug)
Dose Expansion D
Head and Neck Squamous Cell Carcinoma (HNSCC)
干预措施: REGN7075 (Drug)
Dose Expansion A
Triple Negative Breast Cancer (TNBC)
干预措施: Cemiplimab (Drug)
Dose Expansion B
Cutaneous Squamous Cell Carcinoma (CSCC)
干预措施: REGN7075 (Drug)
Dose Expansion E
Microsatellite Stable-Colorectal Cancer (MSS-CRC), with Active Liver Metastases and/or Active Peritoneal Metastases
干预措施: REGN7075 (Drug)
Dose Expansion G
Epidermal Growth Factor Receptor (EGFR) -mutant NSCLC Post Third Generation tyrosine kinase inhibitor (TKI)
干预措施: REGN7075 (Drug)
Dose Expansion C
Non-Small Cell Lung Cancer (NSCLC)
干预措施: REGN7075 (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to 5 years
Dose expansion
Incidence and severity of grade ≥3 laboratory abnormalities
时间窗: Approximately 90 days from last dose; up to 5 years
Dose escalation
The incidence of Dose-Limiting Toxicities (DLTs) during the DLT period
时间窗: Up to 6 weeks
Dose escalation
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Approximately 90 days from last dose; up to 5 years
Dose escalation
Incidence and severity of Adverse Events of Special Interest (AESIs)
时间窗: Approximately 90 days from last dose; up to 5 years
Dose escalation
Incidence and severity of Serious Adverse Events (SAEs)
时间窗: Approximately 90 days from last dose; up to 5 years
Dose escalation
次要结局
- The incidence and severity of AESIs(Approximately 90 days from last dose; up to 5 years)
- Patient reported Quality of Life (QoL) per EORTC QLQ-BR23 in breast cancer patients(Approximately 90 days from last dose; up to 5 years)
- Overall survival (OS)(Up to 5 years)
- Incidence of ADA to cemiplimab(Approximately 90 days from last dose; up to 5 years)
- The incidence and severity of TEAEs(Approximately 90 days from last dose; up to 5 years)
- The incidence and severity of SAEs(Approximately 90 days from last dose; up to 5 years)
- Patient reported Quality of Life (QoL) per EQ-5D-5L(Approximately 90 days from last dose; up to 5 years)
- Patient reported symptoms per EORTC QLQ-C30(Approximately 90 days from last dose; up to 5 years)
- Patient reported symptoms per EORTC QLQ-BR23 in breast cancer patients(Approximately 90 days from last dose; up to 5 years)
- Patient reported symptoms per EQ-5D-5L(Approximately 90 days from last dose; up to 5 years)
- Patient reported functioning per EORTC QLQ-LC13 in NSCLC patients(Approximately 90 days from last dose; up to 5 years)
- ORR(Up to 5 years)
- Duration of Response (DOR)(Up to 5 years)
- Patient reported Quality of Life (QoL) per EORTC QLQ-CR29 in CRC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reported symptoms per EORTC QLQ-HN35 in HNSCC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reported functioning per EORTC QLQ-BR23 in breast cancer patients(Approximately 90 days from last dose; up to 5 years)
- The incidence and severity of grade ≥3 laboratory abnormalities(Approximately 90 days from last dose; up to 5 years)
- Patient reported Quality of Life (QoL) per EORTC QLQ-HN35 in HNSCC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reported symptoms per EORTC QLQ-LC13 in NSCLC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reporting general health status per EORTC QLQ-LC13 in NSCLC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reporting general health status per EORTC QLQ-HN35 in HNSCC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reported Quality of Life (QoL) per EORTC QLQ-LC13 in NSCLC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reported symptoms per EORTC QLQ-CR29 in CRC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reported functioning per EORTC QLQ-C30(Approximately 90 days from last dose; up to 5 years)
- Patient reported functioning per EORTC QLQ-CR29 in CRC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reported functioning per EORTC QLQ-HN35 in HNSCC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reporting general health status per EORTC QLQ-CR29 in CRC patients(Approximately 90 days from last dose; up to 5 years)
- Patient reporting general health status per EQ-5D-5L(Approximately 90 days from last dose; up to 5 years)
- Patient reported functioning per EQ-5D-5L(Approximately 90 days from last dose; up to 5 years)
- Patient reporting general health status per EORTC QLQ-C30(Approximately 90 days from last dose; up to 5 years)
- Patient reporting general health status per EORTC QLQ-BR23 in breast cancer patients(Approximately 90 days from last dose; up to 5 years)
- Concentrations of marlotamig in serum(Up to 5 years)
- Progression Free Survival (PFS)(Up to 5 years)
- Disease Control Rate (DCR)(Up to 5 years)
- Complete Response (CR) rate(Up to 5 years)
- Incidence of Anti-Drug Antibodies (ADA) to marlotamig(Approximately 90 days from last dose; up to 5 years)
- Magnitude of ADA to marlotamig(Approximately 90 days from last dose; up to 5 years)
- Magnitude of ADA to cemiplimab(Approximately 90 days from last dose; up to 5 years)
- Patient reported Quality of Life (QoL) per European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30(Approximately 90 days from last dose; up to 5 years)