Study of REGN2810 (Anti-PD-1) in Patients With Advanced Malignancies

Study Overview
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Brief Summary
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This is a phase 1, open-label, multicenter, ascending-dose escalation study of cemiplimab, alone and in combination with other anti-cancer therapies in patients with advanced malignancies.

Official Title
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A First-in-Human Study of Repeat Dosing With REGN2810, a Monoclonal, Fully Human Antibody to Programmed Death - 1 (PD-1), as Single Therapy and in Combination With Other Anti-Cancer Therapies in Patients With Advanced Malignancies

Conditions
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Advanced Cancer, Advanced Malignancies

Intervention / Treatment
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* Drug: Cemiplimab
* Radiation: Hypofractionated radiotherapy
* Drug: Cyclophosphamide
* Drug: Docetaxel
* Drug: Carboplatin
* Drug: GM-CSF
* Drug: Paclitaxel
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically or cytologically confirmed diagnosis of malignancy with demonstrated progression of a solid tumor (non-lymphoma) with no alternative standard-of-care therapeutic option (certain exceptions may apply). At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for response assessment (certain exceptions may apply) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Key Exclusion Criteria: Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement or psoriasis that does not require systemic treatment. Prior treatment with an agent that blocks the programmed death-1/ programmed death-ligand 1 (PD-1/PD-L1 pathway) (certain exceptions may apply) Prior treatment with other immune modulating agents within fewer than 4 weeks prior to the first dose of cemiplimab. Examples of immune modulating agents include blockers of CTLA-4, 4-1BB (CD137), OX-40, therapeutic vaccines, or cytokine treatments. Untreated brain metastasis(es) that may be considered active. Patients with previously treated brain metastases may participate provided they are stable (i.e., without evidence of progression by imaging for at least 6 weeks prior to the first dose of study treatment, and any neurologic symptoms have returned to baseline), and there is no evidence of new or enlarging brain metastases, and the patient does not require any systemic corticosteroids for management of brain metastases within 4 weeks prior to the first dose of cemiplimab (certain exceptions may apply). Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab The information provided above is not intended to contain all considerations relevant to potential participation in a clinical trial, therefore not all inclusion/ exclusion criteria are listed.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy Cohort<br>Cemiplimab will be administered alone | Drug: Cemiplimab<br> <br> * Other names: Libtayo;|
| Experimental: Dual Combination Cohorts<br>Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy Doses of cemiplimab will be administered in combination with Cyclophosphamide Doses of cemiplimab will be administered in combination with Docetaxel | Drug: Cemiplimab<br> <br> * Other names: Libtayo;Radiation: Hypofractionated radiotherapy<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Docetaxel<br> <br> |
| Experimental: Triple Combination Cohorts<br>Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus Cyclophosphamide Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF Doses of cemiplimab will be administered in combination with Carboplatin plus Paclitaxel Doses of cemiplimab will be administered in combination with Carboplatin plus Pemetrexed Doses of cemiplimab will be administered in combination with Carboplatin plus Docetaxel | Drug: Cemiplimab<br> <br> * Other names: Libtayo;Radiation: Hypofractionated radiotherapy<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Docetaxel<br> <br> Drug: Carboplatin<br> <br> Drug: GM-CSF<br> <br> * Other names: LEUKINE®;Drug: Paclitaxel<br> <br> Drug: Pemetrexed<br> <br> |
| Experimental: Quadruple Combination Cohorts<br>Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF plus Cyclophosphamide | Drug: Cemiplimab<br> <br> * Other names: Libtayo;Radiation: Hypofractionated radiotherapy<br> <br> Drug: Cyclophosphamide<br> <br> Drug: GM-CSF<br> <br> * Other names: LEUKINE®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | Primary safety variables include incidence and severity of TEAEs, abnormal laboratory findings and number of participants with dose limiting toxicities (DLTs) | Change from baseline to week 48 | 
| Incidence of abnormal laboratory findings |  | Change from baseline to week 48 | 
| Number of participants with dose limiting toxicities (DLTs) |  | Change from baseline to 28 days after first dose of cemiplimab | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Evaluation Criteria in Solid Tumors (RECIST) as measured by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) |  | Change from baseline to week 48 | 
| Immune-Related Response Criteria (irRC) applied to RECIST measurements |  | Change from baseline to week 48 | 
| Incidence of development of anti-cemiplimab antibodies |  | Up to week 48 | 
| Antitumor activity measured by progression-free survival (PFS) |  | Up to 72 weeks | 
| Antitumor activity measured by overall survival |  | Up to 249 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced cancerous growth