A Trial to Find Out How Safe REGN7075 is and How Well it Works in Combination With Cemiplimab for Adult Participants With Advanced Cancers (COMBINE-EGFR-1)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: Platinum-based doublet chemotherapy; Drug: Bevacizumab; Drug: REGN7075; Drug: Trifluridine-tipiracil; Drug: Cemiplimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04626635

2022-501234-37-00 (Other Identifier)

R7075-ONC-2009

Details and patient eligibility

About

This study is researching an investigational drug called 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 REGN7075 is by itself and in combination with cemiplimab (with or without chemotherapy), and to find out what is the best dose of REGN7075 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 REGN7075 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 REGN7075 by itself and in combination with cemiplimab with or without chemotherapy
• How REGN7075 works in the body by itself and in combination with cemiplimab with or without chemotherapy
• How much REGN7075 is present in the blood when given by itself and in combination with cemiplimab with or without chemotherapy
• To see if REGN7075 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

Enrollment: 933 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
2. Has histologically or cytologically confirmed cancer that meets criteria as defined in the protocol
3. 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
4. Has at least 1 lesion that meets study criteria as defined in the protocol
5. Willing to provide tumor tissue from newly obtained biopsy (at a minimum core biopsy) from a tumor site that has not been previously irradiated
6. Has adequate organ and bone marrow function as defined in the protocol
7. In the judgement of the investigator, has a life expectancy of at least 3 months

Key Exclusion Criteria:

1. Is currently participating in another study of a therapeutic agent
2. 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
3. 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
4. Has received recent anti-epidermal growth factor receptor (EGFR) antibody therapy as defined in the protocol
5. 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
6. Has received any previous systemic, non-immunomodulatory biologic therapy within 4 weeks of first administration of study drug.
7. Has had prior anti-cancer immunotherapy within 5 half-lives prior to study drug as defined in the protocol
8. Has second malignancy that is progressing or requires active treatment as defined in the protocol
9. 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
10. 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
11. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression
12. Has encephalitis, meningitis, organic brain disease (eg, Parkinson's disease) or uncontrolled seizures within 1 year prior to the first dose of study drug
13. Has any ongoing inflammatory skin disease as defined in the protocol

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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933 participants in 11 patient groups

Dose Escalation

Experimental group

Description:

Variety of mixed advanced solid tumor types

Treatment:

Drug: Cemiplimab

Drug: REGN7075

Dose Expansion A

Experimental group

Description:

Triple Negative Breast Cancer (TNBC)

Treatment:

Drug: Cemiplimab

Drug: REGN7075

Dose Expansion B

Experimental group

Description:

Cutaneous Squamous Cell Carcinoma (CSCC)

Treatment:

Drug: Cemiplimab

Drug: REGN7075

Dose Expansion C

Experimental group

Description:

Non-Small Cell Lung Cancer (NSCLC)

Treatment:

Drug: Cemiplimab

Drug: REGN7075

Drug: Platinum-based doublet chemotherapy

Dose Expansion D

Experimental group

Description:

Head and Neck Squamous Cell Carcinoma (HNSCC)

Treatment:

Drug: Cemiplimab

Drug: REGN7075

Dose Expansion E

Experimental group

Description:

Microsatellite Stable-Colorectal Cancer (MSS-CRC), with Active Liver Metastases and/or Active Peritoneal Metastases

Treatment:

Drug: Cemiplimab

Drug: REGN7075

Dose Expansion F

Experimental group

Description:

MSS-CRC with Isolated Lung/Lymph Node Metastases (no active liver and no active peritoneal metastases)

Treatment:

Drug: Cemiplimab

Drug: REGN7075

Dose Expansion G

Experimental group

Description:

Epidermal Growth Factor Receptor (EGFR) -mutant NSCLC Post Third Generation tyrosine kinase inhibitor (TKI)

Treatment:

Drug: Cemiplimab

Drug: REGN7075

Drug: Platinum-based doublet chemotherapy

Dose Expansion H

Experimental group

Description:

EGFR-mutant NSCLC Post Third Generation TKI and Post Platinum-Doublet Chemotherapy

Treatment:

Drug: Cemiplimab

Drug: REGN7075

Dose Expansion I

Experimental group

Description:

Third-line (3L) MSS-CRC with Active Liver Metastases

Treatment:

Drug: Cemiplimab

Drug: Trifluridine-tipiracil

Drug: REGN7075

Drug: Bevacizumab

Dose Expansion J

Experimental group

Description:

3L MSS-CRC without Active Liver Metastases

Treatment:

Drug: Cemiplimab

Drug: Trifluridine-tipiracil

Drug: REGN7075

Drug: Bevacizumab