A Trial to Find Out How Safe REGN7075 is and How Well it Works in Combination With Cemiplimab for Adult Participants With Advanced Cancers

Advanced Solid Tumors Clinical Trial

— COMBINE-EGFR-1  

Official title:

A Phase 1/2 Study of REGN7075 (EGFRxCD28 Costimulatory Bispecific Antibody) in Combination With Cemiplimab in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04626635
• Other study ID #: R7075-ONC-2009
• Secondary ID: 2022-501234-37-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 21, 2020
• Est. completion date: December 12, 2026

Study information

• Verified date: October 2023
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 your 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 your cancer by controlling the proliferation of tumor cells to shrink your tumor.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 769
• Est. completion date: December 12, 2026
• Est. primary completion date: August 19, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Drug:
• REGN7075
Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)
• cemiplimab
administered concomitantly Q3W by IV infusion or SC injection
• Platinum-based doublet chemotherapy
administered IV Q3W

Locations

Country	Name	City	State
France	Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux
Spain	Hospital Universitari General de Catalunya	Barcelona
Spain	Hospital Clinico Universitario-University of Valencia	Valencia
Turkey	Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi	Ankara
Turkey	Istanbul Medeniyet University Prof.Dr.Suleyman Yalcin Sehir Hospital	Istanbul
Turkey	Baskent Universitesi	Yuregir	Adana
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	START Midwest - Cancer & Hematology Centers of Western Michigan, PC	Grand Rapids	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Tennessee Oncology Sarah Cannon Research Institute	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	START - South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	The Regents of the University of California, San Francisco (UCSF)	San Francisco	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of dose-limiting toxicities (DLTs) during the DLT period	Dose escalation	Up to 6 weeks
Primary	Incidence and severity of treatment emergent adverse events (TEAEs)	Dose escalation	Approximately 90 days from last dose; up to 5 years
Primary	Incidence and severity of adverse events of special interest (AESIs)	Dose escalation	Approximately 90 days from last dose; up to 5 years
Primary	Incidence and severity of serious adverse events (SAEs)	Dose escalation	Approximately 90 days from last dose; up to 5 years
Primary	Incidence and severity of grade =3 laboratory abnormalities	Dose escalation	Approximately 90 days from last dose; up to 5 years
Primary	Objective Response Rate (ORR)	Dose expansion	Up to 5 years
Secondary	Concentrations of REGN7075 in serum	Dose escalation and dose expansion	Up to 5 years
Secondary	ORR	Dose escalation	Up to 5 years
Secondary	Progression free survival (PFS)	Dose escalation and dose expansion	Up to 5 years
Secondary	Duration of Response (DOR)	Dose escalation and dose expansion	Up to 5 years
Secondary	Disease control rate (DCR)	Dose escalation and dose expansion	Up to 5 years
Secondary	Complete response (CR) rate	Dose escalation and dose expansion	Up to 5 years
Secondary	Overall survival (OS)	Dose escalation and dose expansion	Up to 5 years
Secondary	Incidence of anti-drug antibodies (ADA) to REGN7075	Dose escalation and dose expansion	Approximately 90 days from last dose; up to 5 years
Secondary	Titers of ADA to REGN7075	Dose escalation and dose expansion	Approximately 90 days from last dose; up to 5 years
Secondary	Incidence of ADA to cemiplimab	Dose escalation and dose expansion	Approximately 90 days from last dose; up to 5 years
Secondary	Titers of ADA to cemiplimab	Dose escalation and dose expansion	Approximately 90 days from last dose; up to 5 years
Secondary	The incidence and severity of TEAEs	Dose expansion	Approximately 90 days from last dose; up to 5 years
Secondary	The incidence and severity of AESIs	Dose expansion	Approximately 90 days from last dose; up to 5 years
Secondary	The incidence and severity of SAEs	Dose expansion	Approximately 90 days from last dose; up to 5 years
Secondary	The incidence and severity of grade =3 laboratory abnormalities	Dose expansion	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported Quality of Life (QoL) per EORTC QLQ-C30	EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported Quality of Life (QoL) per EORTC QLQ-CR29 in CRC patients	The EORTC QLQ CR-29 questionnaire consists of 29 items (Likert scale), with a response scale for each of them from 1 to 4, with the following structure: 1 = Not at All 2 = A little; 3 = Quite a Bit; 4 = Very much. The QLQ-CR29 has five functional and 18 symptom scales. It contains four subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items (urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, anxiety, weight, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, sexual interest (men), impotence, sexual interest (women), and dyspareunia). Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported Quality of Life (QoL) per EORTC QLQ-BR23 in breast cancer patients	The EORTC-QLQ-BR23 includes functional scales (body image, sexual functioning, sexual enjoyment, and future perspective) and single item symptoms scales (systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss). Questions use 4-point Likert scale (1 'Not at All' to 4 'Very Much'). Scores average and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported Quality of Life (QoL) per EORTC QLQ-LC13 in NSCLC patients	The EORTC QLQ-LC13 is a 13-item, disease-specific module which assesses quality of life across multiple scales, including dyspnea, cough and chest pain.; The scale for EORTC-QLQ-LC13 is 1-4 for most outcome measures of systems, with 1 rated as "not at all" and 4 rated as "very much".	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported Quality of Life (QoL) per EORTC QLQ-HN35 in HNSCC patients	The EORTC QLQ-HN35 is a 35-item, disease-specific module which assesses quality of life across multiple scales, including pain, swallowing, and senses.; The questionnaire has 35 Likert type questions in total and the evaluation is made by giving the score of None: 1, A little: 2, Quite: 3, A lot: 4.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported Quality of Life (QoL) per EQ-5D-5L	The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported symptoms per EORTC QLQ-C30	EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported symptoms per EORTC QLQ-CR29 in CRC patients	The EORTC QLQ CR-29 questionnaire consists of 29 items (Likert scale), with a response scale for each of them from 1 to 4, with the following structure: 1 = Not at All 2 = A little; 3 = Quite a Bit; 4 = Very much. The QLQ-CR29 has five functional and 18 symptom scales. It contains four subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items (urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, anxiety, weight, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, sexual interest (men), impotence, sexual interest (women), and dyspareunia). . Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported symptoms per EORTC QLQ-BR23 in breast cancer patients	The EORTC-QLQ-BR23 includes functional scales (body image, sexual functioning, sexual enjoyment, and future perspective) and single item symptoms scales (systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss). Questions use 4-point Likert scale (1 'Not at All' to 4 'Very Much'). Scores average and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported symptoms per EORTC QLQ-LC13 in NSCLC patients	The EORTC QLQ-LC13 is a 13-item, disease-specific module which assesses quality of life across multiple scales, including dyspnea, cough and chest pain.; The scale for EORTC-QLQ-LC13 is 1-4 for most outcome measures of systems, with 1 rated as "not at all" and 4 rated as "very much".	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported symptoms per EORTC QLQ-HN35 in HNSCC patients	The EORTC QLQ-HN35 is a 35-item, disease-specific module which assesses quality of life across multiple scales, including pain, swallowing, and senses.; The questionnaire has 35 Likert type questions in total and the evaluation is made by giving the score of None: 1, A little: 2, Quite: 3, A lot: 4.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported symptoms per EQ-5D-5L	The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported functioning per EORTC QLQ-C30	EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported functioning per EORTC QLQ-CR29 in CRC patients	The EORTC QLQ CR-29 questionnaire consists of 29 items (Likert scale), with a response scale for each of them from 1 to 4, with the following structure: 1 = Not at All 2 = A little; 3 = Quite a Bit; 4 = Very much. The QLQ-CR29 has five functional and 18 symptom scales. It contains four subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items (urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, anxiety, weight, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, sexual interest (men), impotence, sexual interest (women), and dyspareunia). Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported functioning per EORTC QLQ-BR23 in breast cancer patients	The EORTC-QLQ-BR23 includes functional scales (body image, sexual functioning, sexual enjoyment, and future perspective) and single item symptoms scales (systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss). Questions use 4-point Likert scale (1 'Not at All' to 4 'Very Much'). Scores average and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported functioning per EORTC QLQ-LC13 in NSCLC patients	The EORTC QLQ-LC13 is a 13-item, disease-specific module which assesses quality of life across multiple scales, including dyspnea, cough and chest pain.; The scale for EORTC-QLQ-LC13 is 1-4 for most outcome measures of systems, with 1 rated as "not at all" and 4 rated as "very much".	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported functioning per EORTC QLQ-HN35 in HNSCC patients	The EORTC QLQ-HN35 is a 35-item, disease-specific module which assesses quality of life across multiple scales, including pain, swallowing, and senses.; The questionnaire has 35 Likert type questions in total and the evaluation is made by giving the score of None: 1, A little: 2, Quite: 3, A lot: 4.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reported functioning per EQ-5D-5L	The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reporting general health status per EORTC QLQ-C30	EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reporting general health status per EORTC QLQ-CR29 in CRC patients	The EORTC QLQ CR-29 questionnaire consists of 29 items (Likert scale), with a response scale for each of them from 1 to 4, with the following structure: 1 = Not at All 2 = A little; 3 = Quite a Bit; 4 = Very much. The QLQ-CR29 has five functional and 18 symptom scales. It contains four subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items (urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, anxiety, weight, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, sexual interest (men), impotence, sexual interest (women), and dyspareunia). Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reporting general health status per EORTC QLQ-BR23 in breast cancer patients	The EORTC-QLQ-BR23 includes functional scales (body image, sexual functioning, sexual enjoyment, and future perspective) and single item symptoms scales (systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss). Questions use 4-point Likert scale (1 'Not at All' to 4 'Very Much'). Scores average and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reporting general health status per EORTC QLQ-LC13 in NSCLC patients	The EORTC QLQ-LC13 is a 13-item, disease-specific module which assesses quality of life across multiple scales, including dyspnea, cough and chest pain.; The scale for EORTC-QLQ-LC13 is 1-4 for most outcome measures of systems, with 1 rated as "not at all" and 4 rated as "very much".	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reporting general health status per EORTC QLQ-HN35 in HNSCC patients	The EORTC QLQ-HN35 is a 35-item, disease-specific module which assesses quality of life across multiple scales, including pain, swallowing, and senses.; The questionnaire has 35 Likert type questions in total and the evaluation is made by giving the score of None: 1, A little: 2, Quite: 3, A lot: 4.	Approximately 90 days from last dose; up to 5 years
Secondary	Patient reporting general health status per EQ-5D-5L	The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	Approximately 90 days from last dose; up to 5 years