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

Study Overview
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Brief Summary
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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.

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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: REGN7075
* Drug: cemiplimab
* Drug: Platinum-based doublet chemotherapy


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 Key Exclusion Criteria: 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, 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Variety of mixed advanced solid tumor types | Drug: REGN7075<br>* Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)<br>Drug: cemiplimab<br>* administered concomitantly Q3W by IV infusion or SC injection<br>* Other names: Libtayo;|
| Experimental: Dose Expansion A<br>Triple Negative Breast Cancer (TNBC) | Drug: REGN7075<br>* Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)<br>Drug: cemiplimab<br>* administered concomitantly Q3W by IV infusion or SC injection<br>* Other names: Libtayo;|
| Experimental: Dose Expansion B<br>Cutaneous Squamous Cell Carcinoma (CSCC) | Drug: REGN7075<br>* Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)<br>Drug: cemiplimab<br>* administered concomitantly Q3W by IV infusion or SC injection<br>* Other names: Libtayo;|
| Experimental: Dose Expansion C<br>Non-Small Cell Lung Cancer (NSCLC) | Drug: REGN7075<br>* Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)<br>Drug: cemiplimab<br>* administered concomitantly Q3W by IV infusion or SC injection<br>* Other names: Libtayo;Drug: Platinum-based doublet chemotherapy<br>* administered IV Q3W<br>|
| Experimental: Dose Expansion D<br>Head and Neck Squamous Cell Carcinoma (HNSCC) | Drug: REGN7075<br>* Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)<br>Drug: cemiplimab<br>* administered concomitantly Q3W by IV infusion or SC injection<br>* Other names: Libtayo;|
| Experimental: Dose Expansion E<br>Microsatellite Stable-Colorectal Cancer (MSS-CRC), with Active Liver Metastases and/or Active Peritoneal Metastases | Drug: REGN7075<br>* Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)<br>Drug: cemiplimab<br>* administered concomitantly Q3W by IV infusion or SC injection<br>* Other names: Libtayo;|
| Experimental: Dose Expansion F<br>MSS-CRC with Isolated Lung/Lymph Node Metastases (no active liver and no active peritoneal metastases) | Drug: REGN7075<br>* Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)<br>Drug: cemiplimab<br>* administered concomitantly Q3W by IV infusion or SC injection<br>* Other names: Libtayo;|
| Experimental: Dose Expansion G<br>Epidermal Growth Factor Receptor (EGFR) -mutant NSCLC Post Third Generation tyrosine kinase inhibitor (TKI) | Drug: REGN7075<br>* Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)<br>Drug: cemiplimab<br>* administered concomitantly Q3W by IV infusion or SC injection<br>* Other names: Libtayo;Drug: Platinum-based doublet chemotherapy<br>* administered IV Q3W<br>|
| Experimental: Dose Expansion H<br>EGFR-mutant NSCLC Post Third Generation TKI and Post Platinum-Doublet Chemotherapy | Drug: REGN7075<br>* Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)<br>Drug: cemiplimab<br>* administered concomitantly Q3W by IV infusion or SC injection<br>* Other names: Libtayo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of REGN7075 in serum | Dose escalation and dose expansion | Up to 5 years | 
| ORR | Dose escalation | Up to 5 years | 
| Progression free survival (PFS) | Dose escalation and dose expansion | Up to 5 years | 
| Duration of Response (DOR) | 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 | 
| Overall survival (OS) | Dose escalation and dose expansion | Up to 5 years | 
| Incidence of anti-drug antibodies (ADA) to REGN7075 | Dose escalation and dose expansion | Approximately 90 days from last dose; up to 5 years | 
| Titers of ADA to REGN7075 | Dose escalation and dose expansion | Approximately 90 days from last dose; up to 5 years | 
| Incidence of ADA to cemiplimab | Dose escalation and dose expansion | Approximately 90 days from last dose; up to 5 years | 
| Titers 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-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 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-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 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-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-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-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-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-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-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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Variety of mixed advanced solid tumor types, First in Human (FIH)