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

Regeneron Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Advanced Malignancies; Advanced Cancer

Treatments: Drug: Cyclophosphamide; Drug: Cemiplimab; Drug: Docetaxel; Drug: GM-CSF; Radiation: Hypofractionated radiotherapy; Drug: Paclitaxel; Drug: Pemetrexed; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02383212

2015-002132-41 (EudraCT Number)

R2810-ONC-1423

Details and patient eligibility

About

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.

Enrollment: 398 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. 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).
2. At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for response assessment (certain exceptions may apply)
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Key Exclusion Criteria:

1. 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.
2. Prior treatment with an agent that blocks the programmed death-1/ programmed death-ligand 1 (PD-1/PD-L1 pathway) (certain exceptions may apply)
3. 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.
4. 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).
5. 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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398 participants in 4 patient groups

Monotherapy Cohort

Experimental group

Description:

Cemiplimab will be administered alone

Treatment:

Drug: Cemiplimab

Dual Combination Cohorts

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Drug: Docetaxel

Drug: Cemiplimab

Radiation: Hypofractionated radiotherapy

Triple Combination Cohorts

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Drug: Pemetrexed

Drug: Carboplatin

Drug: GM-CSF

Drug: Docetaxel

Drug: Cemiplimab

Radiation: Hypofractionated radiotherapy

Drug: Paclitaxel

Quadruple Combination Cohorts

Experimental group

Description:

Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF plus Cyclophosphamide

Treatment:

Drug: Cyclophosphamide

Drug: GM-CSF

Drug: Cemiplimab

Radiation: Hypofractionated radiotherapy