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)

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

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: REGN7075; Drug: Cemiplimab; Drug: Platinum-based doublet chemotherapy; Drug: Bevacizumab; Drug: Trifluridine-tipiracil

• Study Type: Interventional
• Enrollment (Actual): 548
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Hospital Paris Saint-Joseph
  • Auvergne-Rhone
    • Lyon, Auvergne-Rhone, France, 69008
      • Centre Leon Berard (CLB) - Centre de Recherche en Cancerologie Lyon-Est (CRCL)
  • Auvergne-Rhône
    • Pierre-Bénite, Auvergne-Rhône, France, 69310
      • Hôpital Lyon Sud
  • Bourgogne-Franche-Comté
    • Dijon, Bourgogne-Franche-Comté, France, 21034
      • Centre Georges François Leclerc
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Institut Claudius Regaud, IUCT-Oncopole
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59000
      • Centre Hospitalier Universitaire (CHU) de Lille
  • New Aquitaine
    • Bordeaux, New Aquitaine, France, 33076
      • Institut Bergonie
    • Poitiers, New Aquitaine, France, 86021
      • Centre Hospitalier Universitaire (CHU) de Poitiers
  • Pays de la Loire Region
    • Nantes, Pays de la Loire Region, France, 44093
      • Nantes University Hospital
  • Provence Alpes Cote dAzur
    • Nice, Provence Alpes Cote dAzur, France, 06189
      • Centre Antoine Lacassagne
  • Île-de-France Region
    • Saint-Mandé, Île-de-France Region, France, 94240
      • Begin Army Instruction Hospital
    • Villejuif, Île-de-France Region, France, 94800
      • Gustave Roussy
• Israel
  • Beersheba, Israel, 84101
    • Soroka University Medical Center
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 91220
    • Hadassah Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Central District
    • Ramat Gan, Central District, Israel, 5265601
      • Sheba Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Netherlands Cancer Institute
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC
• Poland
  • Wielkopolska
    • Poznan, Wielkopolska, Poland, 60-693
      • Medpolonia Sp. z o.o.
  • Zach
    • Szczecin, Zach, Poland, 70-784
      • Dom Lekarski SA
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital 12 De Octubre
  • Madrid, Spain, 28002
    • Genesis Care Hospital San Francisco de Asis
  • Valencia, Spain, 28040
    • Hospital Clinico Universitario - University of Valencia
  • Barcelona
    • Sant Cugat del Vallès, Barcelona, Spain, 08195
      • Hospital General De Catalunya
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quiron Salud Madrid
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06200
    • Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
  • Istanbul, Turkey (Türkiye), 81450
    • Istanbul Medeniyet University - Prof Dr Suleyman Yalcin Sehir Hospital
  • Mersin, Turkey (Türkiye), 33343
    • Ciftlikkoy Campus Yenisehir Mersin
  • Adana
    • Yüreğir, Adana, Turkey (Türkiye), 01120
      • Baskent Universitesi
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles (UCLA) Medical Center
    • Los Angeles, California, United States, 90067
      • Valkyrie Clinical Trials
    • San Francisco, California, United States, 94118
      • The Regents of the University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Cancer Pavilion - Lung Cancer Clinic
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida Health
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest - Cancer & Hematology Centers of Western Michigan, PC
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Columbus, Ohio, United States, 43212
      • The Stefanie Spielman Comprehensive Breast Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute - 25th Ave
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Oncology And Hematology
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington/Fred Hutchinson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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, Central Nervous System (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Variety of mixed advanced solid tumor types	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo
Experimental: Dose Expansion A; Triple Negative Breast Cancer (TNBC)	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo
Experimental: Dose Expansion B; Cutaneous Squamous Cell Carcinoma (CSCC)	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo
Experimental: Dose Expansion C; Non-Small Cell Lung Cancer (NSCLC)	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo; Drug: Platinum-based doublet chemotherapy; Administered IV Q3W
Experimental: Dose Expansion D; Head and Neck Squamous Cell Carcinoma (HNSCC)	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo
Experimental: Dose Expansion E; Microsatellite Stable-Colorectal Cancer (MSS-CRC), with Active Liver Metastases and/or Active Peritoneal Metastases	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo
Experimental: Dose Expansion F; MSS-CRC with Isolated Lung/Lymph Node Metastases (no active liver and no active peritoneal metastases)	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo
Experimental: Dose Expansion G; Epidermal Growth Factor Receptor (EGFR) -mutant NSCLC Post Third Generation tyrosine kinase inhibitor (TKI)	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo; Drug: Platinum-based doublet chemotherapy; Administered IV Q3W
Experimental: Dose Expansion H; EGFR-mutant NSCLC Post Third Generation TKI and Post Platinum-Doublet Chemotherapy	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo
Experimental: Dose Expansion I; Third-line (3L) MSS-CRC with Active Liver Metastases	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo; Drug: Bevacizumab; Administered per protocol; Drug: Trifluridine-tipiracil; Administered per protocol
Experimental: Dose Expansion J; 3L MSS-CRC without Active Liver Metastases	Drug: REGN7075; Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W); Other Names: marlotamig; Drug: Cemiplimab; Administered concomitantly Q3W by IV infusion or SC injection; Other Names: REGN2810; Libtayo; Drug: Bevacizumab; Administered per protocol; Drug: Trifluridine-tipiracil; Administered per protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of grade ≥3 laboratory abnormalities	Dose escalation	Approximately 90 days from last dose; up to 5 years
Objective Response Rate (ORR)	Dose expansion	Up to 5 years
The incidence of Dose-Limiting Toxicities (DLTs) during the DLT period	Dose escalation	Up to 6 weeks
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)	Dose escalation	Approximately 90 days from last dose; up to 5 years
Incidence and severity of Adverse Events of Special Interest (AESIs)	Dose escalation	Approximately 90 days from last dose; up to 5 years
Incidence and severity of Serious Adverse Events (SAEs)	Dose escalation	Approximately 90 days from last dose; up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Dose escalation	Up to 5 years
Duration of Response (DOR)	Dose escalation and dose expansion	Up to 5 years
Overall survival (OS)	Dose escalation and dose expansion	Up to 5 years
Incidence of ADA to cemiplimab	Dose escalation and dose expansion	Approximately 90 days from last dose; up to 5 years
The incidence and severity of TEAEs	Dose expansion	Approximately 90 days from last dose; up to 5 years
The incidence and severity of AESIs	Dose expansion	Approximately 90 days from last dose; up to 5 years
The incidence and severity of SAEs	Dose expansion	Approximately 90 days from last dose; up to 5 years
The incidence and severity of grade ≥3 laboratory abnormalities	Dose expansion	Approximately 90 days from last dose; up to 5 years
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Concentrations of marlotamig in serum	Dose escalation and dose expansion	Up to 5 years
Progression Free Survival (PFS)	Dose escalation and dose expansion	Up to 5 years
Disease Control Rate (DCR)	Dose escalation and dose expansion	Up to 5 years
Complete Response (CR) rate	Dose escalation and dose expansion	Up to 5 years
Incidence of Anti-Drug Antibodies (ADA) to marlotamig	Dose escalation and dose expansion	Approximately 90 days from last dose; up to 5 years
Magnitude of ADA to marlotamig	Dose escalation and dose expansion	Approximately 90 days from last dose; up to 5 years
Magnitude of ADA to cemiplimab	Dose escalation and dose expansion	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	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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2020
• Primary Completion (Estimated): November 13, 2026
• Study Completion (Estimated): March 5, 2027

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: First in Human (FIH); Variety of mixed advanced solid tumor types
• Additional Relevant MeSH Terms: Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; trifluridine tipiracil drug combination; cemiplimab
• Other Study ID Numbers: R7075-ONC-2009; 2022-501234-37-00 (Ctis: EU CTR-CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing 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, or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry),
• the legal authority to share the data,
• ensured the ability to protect participant privacy.

• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No