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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer; Advanced Malignancies
• Intervention / Treatment: Drug: Docetaxel; Drug: Cyclophosphamide; Drug: Pemetrexed; Drug: Carboplatin; Drug: Paclitaxel; Drug: GM-CSF; Drug: Cemiplimab; Radiation: Hypofractionated radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 398
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • Peter Maccallum Cancer Centre
• Spain
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain
    • Fundacion Jimenez Diaz
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • MD Anderson Cancer Center
  • Madrid, Spain
    • Hospital Universitario HM Sanchinarro-CIOCC
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain
      • Institut Catala d'Oncologia L'Hospitalet
• United States
  • Arizona
    • Gilbert, Arizona, United States
      • Banner MD Anderson Cancer Center
    • Goodyear, Arizona, United States
      • Western Regional Medical Center
    • Phoenix, Arizona, United States
      • Mayo Clinic
    • Tucson, Arizona, United States
      • University of Arizona Cancer Center
  • California
    • Duarte, California, United States
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
    • Los Angeles, California, United States
      • Ronald Reagan UCLA Medical Center
    • Stanford, California, United States
      • Stanford University
  • Colorado
    • Denver, Colorado, United States
      • Sarah Cannon Research Institute at HealthONE
  • Connecticut
    • Norwalk, Connecticut, United States
      • Norwalk Hospital
  • District of Columbia
    • Washington, District of Columbia, United States
      • Georgetown University Medical Center
  • Florida
    • Tampa, Florida, United States
      • H Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States
      • Winship Cancer Institute, Emory University
  • Illinois
    • Chicago, Illinois, United States
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States
      • Indiana University
  • Kansas
    • Fairway, Kansas, United States
      • University of Kansas Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States
      • Barbara Ann Karmanos Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States
      • Washington University School of Medicine Siteman Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States
      • Nebraska Methodist Hospital
  • New Jersey
    • Hackensack, New Jersey, United States
      • Hackensack University Medical Center
    • New Brunswick, New Jersey, United States
      • Cancer Institute of New Jersey
  • New York
    • New York, New York, United States
      • Columbia University Medical Center
    • New York, New York, United States
      • Weill Cornell Medical College
    • New York, New York, United States
      • Mount Sinai Medical Center
    • New York, New York, United States
      • Laura & Isaac Perlmutter Cancer Center
  • North Carolina
    • Durham, North Carolina, United States
      • Duke Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States
      • University Hospitals Case Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States
      • Providence Portland Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States
      • Penn State Milton S Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center Shadyside
  • Rhode Island
    • Providence, Rhode Island, United States
      • Miriam Hospital
  • Tennessee
    • Nashville, Tennessee, United States
      • Sarah Cannon Research Institute
    • Nashville, Tennessee, United States
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States
      • Mary Crowley Cancer Research Center - Medical City
    • Houston, Texas, United States
      • Baylor College of Medicine
    • Houston, Texas, United States
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States
      • Start South Texas Accelerated Research Therapeutics
  • Washington
    • Tacoma, Washington, United States
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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: Docetaxel; Drug: Cyclophosphamide; Drug: Cemiplimab; Other Names: REGN2810; Libtayo; Radiation: Hypofractionated radiotherapy
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: Docetaxel; Drug: Cyclophosphamide; Drug: Pemetrexed; Drug: Carboplatin; Drug: Paclitaxel; Drug: GM-CSF; Other Names: LEUKINE®; Drug: Cemiplimab; Other Names: REGN2810; Libtayo; Radiation: Hypofractionated radiotherapy
Experimental: Quadruple Combination Cohorts; Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF plus Cyclophosphamide	Drug: Cyclophosphamide; Drug: GM-CSF; Other Names: LEUKINE®; Drug: Cemiplimab; Other Names: REGN2810; Libtayo; Radiation: Hypofractionated radiotherapy

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi

Publications and helpful links

General Publications

• Rischin D, Migden MR, Lim AM, Schmults CD, Khushalani NI, Hughes BGM, Schadendorf D, Dunn LA, Hernandez-Aya L, Chang ALS, Modi B, Hauschild A, Ulrich C, Eigentler T, Stein B, Pavlick AC, Geiger JL, Gutzmer R, Alam M, Okoye E, Mathias M, Jankovic V, Stankevich E, Booth J, Li S, Lowy I, Fury MG, Guminski A. Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing. J Immunother Cancer. 2020 Jun;8(1):e000775. doi: 10.1136/jitc-2020-000775.
• Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS, Rabinowits G, Thai AA, Dunn LA, Hughes BGM, Khushalani NI, Modi B, Schadendorf D, Gao B, Seebach F, Li S, Li J, Mathias M, Booth J, Mohan K, Stankevich E, Babiker HM, Brana I, Gil-Martin M, Homsi J, Johnson ML, Moreno V, Niu J, Owonikoko TK, Papadopoulos KP, Yancopoulos GD, Lowy I, Fury MG. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2018 Jul 26;379(4):341-351. doi: 10.1056/NEJMoa1805131. Epub 2018 Jun 4.
• Babiker H, Brana I, Mahadevan D, Owonikoko T, Calvo E, Rischin D, Moreno V, Papadopoulos KP, Crittenden M, Formenti S, Giralt J, Garrido P, Soria A, Hervas-Moron A, Mohan KK, Fury M, Lowy I, Mathias M, Feng M, Li J, Stankevich E. Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Oncologist. 2021 Sep;26(9):e1508-e1513. doi: 10.1002/onco.13810. Epub 2021 May 22.
• Moreno V, Garrido P, Papadopoulos KP, De Miguel Luken MJ, Gil-Martin M, Aljumaily R, Rosen LS, Rietschel P, Mohan KK, Yoo SY, Stankevich E, Lowy I, Fury MG. Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, as monotherapy in patients with pretreated non-small cell lung cancer (NSCLC): Data from the Phase 1 NSCLC expansion cohort. Lung Cancer. 2021 May;155:151-155. doi: 10.1016/j.lungcan.2021.02.034. Epub 2021 Mar 4.
• Falchook GS, Leidner R, Stankevich E, Piening B, Bifulco C, Lowy I, Fury MG. Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer. 2016 Nov 15;4:70. doi: 10.1186/s40425-016-0176-3. eCollection 2016.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2015
• Primary Completion (Actual): November 18, 2019
• Study Completion (Actual): November 18, 2019

Study Registration Dates

• First Submitted: February 2, 2015
• First Submitted That Met QC Criteria: March 3, 2015
• First Posted (Estimate): March 9, 2015

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 23, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Advanced cancerous growth
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Docetaxel; Cyclophosphamide; Carboplatin; Paclitaxel; Pemetrexed; Cemiplimab
• Other Study ID Numbers: R2810-ONC-1423; 2015-002132-41 (EudraCT Number)