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

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT02383212

Collaborator

Sanofi (Industry)

398

Enrollment

Locations

Arms

57.5

Actual Duration (Months)

8.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer Advanced Malignancies	Drug: Cemiplimab Radiation: Hypofractionated radiotherapy Drug: Cyclophosphamide Drug: Docetaxel Drug: Carboplatin Drug: GM-CSF Drug: Paclitaxel Drug: Pemetrexed	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

398 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 2, 2015

Actual Primary Completion Date :

Nov 18, 2019

Actual Study Completion Date :

Nov 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Monotherapy Cohort Cemiplimab will be administered alone	Drug: Cemiplimab Other Names: REGN2810 Libtayo
Experimental: Dual Combination Cohorts 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 Other Names: REGN2810 Libtayo Radiation: Hypofractionated radiotherapy Drug: Cyclophosphamide Drug: Docetaxel
Experimental: Triple Combination Cohorts 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 Other Names: REGN2810 Libtayo Radiation: Hypofractionated radiotherapy Drug: Cyclophosphamide Drug: Docetaxel Drug: Carboplatin Drug: GM-CSF Other Names: LEUKINE® Drug: Paclitaxel Drug: Pemetrexed
Experimental: Quadruple Combination Cohorts Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF plus Cyclophosphamide	Drug: Cemiplimab Other Names: REGN2810 Libtayo Radiation: Hypofractionated radiotherapy Drug: Cyclophosphamide Drug: GM-CSF Other Names: LEUKINE®

Outcome Measures

Primary Outcome Measures

Incidence of Treatment Emergent Adverse Events (TEAEs) [Change from baseline to week 48]
Primary safety variables include incidence and severity of TEAEs, abnormal laboratory findings and number of participants with dose limiting toxicities (DLTs)
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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States
2	Western Regional Medical Center	Goodyear	Arizona	United States
3	Mayo Clinic	Phoenix	Arizona	United States
4	University of Arizona Cancer Center	Tucson	Arizona	United States
5	City of Hope National Medical Center	Duarte	California	United States
6	The Angeles Clinic and Research Institute	Los Angeles	California	United States	90025
7	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States
8	Stanford University	Stanford	California	United States
9	Sarah Cannon Research Institute at HealthONE	Denver	Colorado	United States
10	Norwalk Hospital	Norwalk	Connecticut	United States
11	Georgetown University Medical Center	Washington	District of Columbia	United States
12	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States
13	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States
14	University of Chicago	Chicago	Illinois	United States
15	Indiana University	Indianapolis	Indiana	United States
16	University of Kansas Cancer Center	Fairway	Kansas	United States
17	Dana Farber Cancer Institute	Boston	Massachusetts	United States
18	Barbara Ann Karmanos Cancer Center	Detroit	Michigan	United States
19	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri	United States
20	Nebraska Methodist Hospital	Omaha	Nebraska	United States
21	Hackensack University Medical Center	Hackensack	New Jersey	United States
22	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States
23	Columbia University Medical Center	New York	New York	United States
24	Laura & Isaac Perlmutter Cancer Center	New York	New York	United States
25	Mount Sinai Medical Center	New York	New York	United States
26	Weill Cornell Medical College	New York	New York	United States
27	Duke Cancer Institute	Durham	North Carolina	United States
28	University Hospitals Case Medical Center	Cleveland	Ohio	United States
29	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States
30	Providence Portland Medical Center	Portland	Oregon	United States
31	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States
32	University of Pittsburgh Medical Center Shadyside	Pittsburgh	Pennsylvania	United States	15232
33	Miriam Hospital	Providence	Rhode Island	United States
34	Sarah Cannon Research Institute	Nashville	Tennessee	United States
35	Vanderbilt University Medical Center	Nashville	Tennessee	United States
36	Mary Crowley Cancer Research Center - Medical City	Dallas	Texas	United States
37	Baylor College of Medicine	Houston	Texas	United States
38	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States
39	START South Texas Accelerated Research Therapeutics	San Antonio	Texas	United States
40	Northwest Medical Specialties	Tacoma	Washington	United States
41	Peter Maccallum Cancer Centre	Melbourne		Australia
42	Institut Catala d'Oncologia L'hospitalet	L'Hospitalet de Llobregat	Barcelona	Spain
43	Hospital Universitario Vall d'Hebron	Barcelona		Spain
44	Fundacion Jimenez Diaz	Madrid		Spain
45	Hospital Universitario HM Sanchinarro-CIOCC	Madrid		Spain
46	Hospital Universitario Ramon y Cajal	Madrid		Spain
47	MD Anderson Cancer Center	Madrid		Spain