Advanced Solid Tumors
Conditions
Keywords
Variety of mixed advanced solid tumor types, First in Human (FIH)
Brief summary
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)
Interventions
DRUGREGN7075
Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)
DRUGCemiplimab
Administered concomitantly Q3W by IV infusion or SC injection
Administered IV Q3W
DRUGBevacizumab
Administered per protocol
Administered per protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 2. Has histologically or cytologically confirmed cancer that meets criteria as defined in the protocol 3. Expansion Cohorts only: Is anti-Programmed cell Death protein-1 (PD-1)/Programmed cell Death Ligand-1 (PD-L1) naïve, defined as never having previously been treated with a drug that targets the PD-1 4. Has at least 1 lesion that meets study criteria as defined in the protocol 5. Willing to provide tumor tissue from newly obtained biopsy (at a minimum core biopsy) from a tumor site that has not been previously irradiated 6. Has adequate organ and bone marrow function as defined in the protocol 7. In the judgement of the investigator, has a life expectancy of at least 3 months Key
Exclusion criteria
1. Is currently participating in another study of a therapeutic agent 2. Has participated in any study of an investigational agent or an investigational device within 4 weeks of the first administration of study drug as defined in the protocol 3. Has received treatment with an approved systemic therapy within 4 weeks of the first administration of study drug or has not yet recovered (ie, grade 1 or baseline) from any acute toxicities 4. Has received recent anti-Epidermal Growth Factor Receptor (EGFR) antibody therapy as defined in the protocol 5. Has received radiation therapy or major surgery within 14 days of the first administration of study drug or has not recovered (ie, grade 1 or baseline) from adverse events 6. Has received any previous systemic, non-immunomodulatory biologic therapy within 4 weeks of first administration of study drug. 7. Has had prior anti-cancer immunotherapy within 5 half-lives prior to study drug as defined in the protocol 8. Has second malignancy that is progressing or requires active treatment as defined in the protocol 9. Has any condition requiring ongoing/continuous corticosteroid therapy (\>10 mg prednisone/day or anti-inflammatory equivalent) within 1-2 weeks prior to the first dose of study drug as defined in the protocol 10. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease or any other condition that required treatment with systemic immunosuppressive treatments as defined in the protocol 11. Has untreated or active primary brain tumor, 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of Dose-Limiting Toxicities (DLTs) during the DLT period | Up to 6 weeks | Dose escalation |
| Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) | Approximately 90 days from last dose; up to 5 years | Dose escalation |
| Incidence and severity of Adverse Events of Special Interest (AESIs) | Approximately 90 days from last dose; up to 5 years | Dose escalation |
| Incidence and severity of Serious Adverse Events (SAEs) | Approximately 90 days from last dose; up to 5 years | Dose escalation |
| Incidence and severity of grade ≥3 laboratory abnormalities | Approximately 90 days from last dose; up to 5 years | Dose escalation |
| Objective Response Rate (ORR) | Up to 5 years | Dose expansion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to 5 years | Dose escalation and dose expansion |
| Disease Control Rate (DCR) | Up to 5 years | Dose escalation and dose expansion |
| Complete Response (CR) rate | Up to 5 years | Dose escalation and dose expansion |
| Overall survival (OS) | Up to 5 years | Dose escalation and dose expansion |
| Incidence of Anti-Drug Antibodies (ADA) to marlotamig | Approximately 90 days from last dose; up to 5 years | Dose escalation and dose expansion |
| Magnitude of ADA to marlotamig | Approximately 90 days from last dose; up to 5 years | Dose escalation and dose expansion |
| Incidence of ADA to cemiplimab | Approximately 90 days from last dose; up to 5 years | Dose escalation and dose expansion |
| Magnitude of ADA to cemiplimab | Approximately 90 days from last dose; up to 5 years | Dose escalation and dose expansion |
| The incidence and severity of TEAEs | Approximately 90 days from last dose; up to 5 years | Dose expansion |
| Patient reported Quality of Life (QoL) per European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported Quality of Life (QoL) per EORTC QLQ-CR29 in CRC patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported Quality of Life (QoL) per EORTC QLQ-BR23 in breast cancer patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported Quality of Life (QoL) per EORTC QLQ-LC13 in NSCLC patients | Approximately 90 days from last dose; up to 5 years | 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". |
| Patient reported Quality of Life (QoL) per EORTC QLQ-HN35 in HNSCC patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported Quality of Life (QoL) per EQ-5D-5L | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported symptoms per EORTC QLQ-C30 | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported symptoms per EORTC QLQ-CR29 in CRC patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported symptoms per EORTC QLQ-BR23 in breast cancer patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported symptoms per EORTC QLQ-LC13 in NSCLC patients | Approximately 90 days from last dose; up to 5 years | 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". |
| Patient reported symptoms per EORTC QLQ-HN35 in HNSCC patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported symptoms per EQ-5D-5L | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported functioning per EORTC QLQ-C30 | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported functioning per EORTC QLQ-CR29 in CRC patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported functioning per EORTC QLQ-BR23 in breast cancer patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported functioning per EORTC QLQ-LC13 in NSCLC patients | Approximately 90 days from last dose; up to 5 years | 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". |
| Patient reported functioning per EORTC QLQ-HN35 in HNSCC patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reported functioning per EQ-5D-5L | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reporting general health status per EORTC QLQ-C30 | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reporting general health status per EORTC QLQ-CR29 in CRC patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reporting general health status per EORTC QLQ-BR23 in breast cancer patients | Approximately 90 days from last dose; up to 5 years | 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. |
| Patient reporting general health status per EORTC QLQ-LC13 in NSCLC patients | Approximately 90 days from last dose; up to 5 years | 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". |
| Patient reporting general health status per EORTC QLQ-HN35 in HNSCC patients | Approximately 90 days from last dose; up to 5 years | 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. |
| The incidence and severity of AESIs | Approximately 90 days from last dose; up to 5 years | Dose expansion |
| Patient reporting general health status per EQ-5D-5L | Approximately 90 days from last dose; up to 5 years | 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. |
| The incidence and severity of SAEs | Approximately 90 days from last dose; up to 5 years | Dose expansion |
| The incidence and severity of grade ≥3 laboratory abnormalities | Approximately 90 days from last dose; up to 5 years | Dose expansion |
| Concentrations of marlotamig in serum | Up to 5 years | Dose escalation and dose expansion |
| ORR | Up to 5 years | Dose escalation |
| Progression Free Survival (PFS) | Up to 5 years | Dose escalation and dose expansion |
Countries
France, Israel, Netherlands, Poland, Spain, Turkey (Türkiye), United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed