REGN7075 in Combination With Cemiplimab in Adult Participants With Advanced Solid Tumors (COMBINE-EGFR-1)

• ClinicalTrials.gov Identifier: NCT04626635
• Recruitment Status: Recruiting
• First Posted: November 12, 2020
• Last Update Posted: December 22, 2021
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: November 6, 2020
• First Posted Date: November 12, 2020
• Last Update Posted Date: December 22, 2021
• Actual Study Start Date: December 21, 2020
• Estimated Primary Completion Date: April 3, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 6, 2020)

• The incidence of dose-limiting toxicities (DLTs) during the DLT period [ Time Frame: Up to 6 weeks ]
  Dose escalation
• Incidence and severity of treatment emergent adverse events (TEAEs) [ Time Frame: Approximately 90 days from last dose; up to 5 years ]
  Dose escalation
• Incidence and severity of adverse events of special interest (AESIs) [ Time Frame: Approximately 90 days from last dose; up to 5 years ]
  Dose escalation
• Incidence and severity of serious adverse events (SAEs) [ Time Frame: Approximately 90 days from last dose; up to 5 years ]
  Dose escalation
• Incidence and severity of grade ≥3 laboratory abnormalities [ Time Frame: Approximately 90 days from last dose; up to 5 years ]
  Dose escalation
• Objective Response Rate (ORR) [ Time Frame: Up to 5 years ]
  Dose expansion

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 6, 2020)

• Drug concentrations of REGN7075 in serum [ Time Frame: Up to 5 years ]
  Dose escalation and dose expansion
• Drug concentrations of cemiplimab [ Time Frame: Up to 5 years ]
  Dose escalation and dose expansion
• ORR [ Time Frame: Up to 5 years ]
  Dose escalation
• Progression free survival (PFS) [ Time Frame: Up to 5 years ]
  Dose escalation and dose expansion
• Duration of Response (DOR) [ Time Frame: Up to 5 years ]
  Dose escalation and dose expansion
• Disease control rate (DCR) [ Time Frame: Up to 5 years ]
  Dose escalation and dose expansion
• Complete response (CR) rate [ Time Frame: Up to 5 years ]
  Dose escalation and dose expansion
• Overall survival (OS) [ Time Frame: Up to 5 years ]
  Dose escalation and dose expansion
• Incidence of anti-drug antibodies (ADA) to REGN7075 [ Time Frame: Approximately 90 days from last dose; up to 5 years ]
  Dose escalation and dose expansion
• Incidence of ADA to cemiplimab [ Time Frame: Approximately 90 days from last dose; up to 5 years ]
  Dose escalation and dose expansion
• The incidence and severity of TEAEs [ Time Frame: Approximately 90 days from last dose; up to 5 years ]
  Dose expansion
• The incidence and severity of AESIs [ Time Frame: Approximately 90 days from last dose; up to 5 years ]
  Dose expansion
• The incidence and severity of SAEs [ Time Frame: Approximately 90 days from last dose; up to 5 years ]
  Dose expansion
• The incidence and severity of grade ≥3 laboratory abnormalities [ Time Frame: Approximately 90 days from last dose; up to 5 years ]
  Dose expansion

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: REGN7075 in Combination With Cemiplimab in Adult Participants With Advanced Solid Tumors
• Official Title: A Phase 1/2 Study of REGN7075 (EGFRxCD28 Costimulatory Bispecific Antibody) in Combination With Cemiplimab in Patients With Advanced Solid Tumors

Brief Summary

The primary objective of the study is:

Dose Escalation:

• To assess the safety and tolerability of a REGN7075 monotherapy lead-in and REGN7075 in combination with cemiplimab in patients with advanced solid tumors

Dose Expansion:

• To assess the preliminary efficacy of REGN7075 in combination with cemiplimab within selected advanced solid tumor-specific cohorts, as measured by objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and/or composite response criteria

The secondary objectives of the study are:

Dose Escalation:

• To characterize the pharmacokinetics (PK) of REGN7075 alone and in combination with cemiplimab
• To assess the preliminary efficacy of REGN7075 in combination with cemiplimab, as measured by ORR, overall survival (OS), progression free survival (PFS), duration of response (DOR), complete response (CR) rate, and disease control rate (DCR) per RECIST 1.1 and/or composite response criteria
• To assess immunogenicity of REGN7075 and cemiplimab

Dose Expansion:

• To assess the preliminary efficacy of REGN7075 in combination with cemiplimab within selected advanced solid tumor-specific cohorts of patients as measured by OS, PFS, DOR, CR rate, and DCR per RECIST 1.1 and/or composite response criteria
• To assess the safety and tolerability of REGN7075 in combination with cemiplimab
• To characterize the PK of REGN7075 alone and in combination with cemiplimab
• To assess immunogenicity to REGN7075 and cemiplimab

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumors

Intervention

• Drug: REGN7075
  Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)
• Drug: cemiplimab
  administered concomitantly Q3W by IV infusion or SC injection
  Other Names:

  • REGN2810
  • Libtayo

Study Arms

• Experimental: Dose Escalation
  Variety of mixed advanced solid tumor types
  Interventions:

  • Drug: REGN7075
  • Drug: cemiplimab
• Experimental: Dose Expansion A
  Microsatellite-Stable Colorectal Cancer (MSS CRC)
  Interventions:

  • Drug: REGN7075
  • Drug: cemiplimab
• Experimental: Dose Expansion B
  Triple Negative Breast Cancer (TNBC)
  Interventions:

  • Drug: REGN7075
  • Drug: cemiplimab
• Experimental: Dose Expansion C
  Cutaneous Squamous Cell Carcinoma (CSCC)
  Interventions:

  • Drug: REGN7075
  • Drug: cemiplimab
• Experimental: Dose Expansion D
  Non-Small Cell Lung Cancer (NSCLC)
  Interventions:

  • Drug: REGN7075
  • Drug: cemiplimab
• Experimental: Dose Expansion E
  Head and Neck Squamous Cell Carcinoma (HNSCC)
  Interventions:

  • Drug: REGN7075
  • Drug: cemiplimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 4, 2021): 402
• Original Estimated Enrollment (submitted: November 6, 2020): 312
• Estimated Study Completion Date: April 3, 2025
• Estimated Primary Completion Date: April 3, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. ≥18 years of age (≥20 years of age for patients enrolled in Japan)
2. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
3. Has histologically or cytologically confirmed cancer that meets criteria as defined in the protocol
4. 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
5. Has at least 1 lesion that meets study criteria as defined in the protocol
6. Willing to provide tumor tissue from newly obtained biopsy (at a minimum core biopsy) from a tumor site that has not been previously irradiated
7. Has adequate organ and bone marrow function as defined in the protocol
8. 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04626635
• Other Study ID Numbers: R7075-ONC-2009
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• URL: https://vivli.org/

• Responsible Party: Regeneron Pharmaceuticals
• Study Sponsor: Regeneron Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: December 2021