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

NCT02383212 | Completed Phase 1

• 2 other identifiers: R2810-ONC-14232015-002132-41
• Study Type: interventional
• Target: 398
• Locations: 3 countries
• Sites: 47

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.

Conditions

Advanced Cancer; Advanced Malignancies

Keywords

Advanced cancerous growth

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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

Study Arms (4)

Monotherapy Cohort

EXPERIMENTAL

Cemiplimab will be administered alone

Drug: Cemiplimab

Dual Combination Cohorts

EXPERIMENTAL

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; Radiation: Hypofractionated radiotherapy; Drug: Cyclophosphamide; Drug: Docetaxel

Triple Combination Cohorts

EXPERIMENTAL

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

Quadruple Combination Cohorts

EXPERIMENTAL

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

Drug: Cemiplimab; Radiation: Hypofractionated radiotherapy; Drug: Cyclophosphamide; Drug: GM-CSF

Interventions

Cemiplimab DRUG

Also known as: REGN2810, Libtayo

Dual Combination Cohorts; Monotherapy Cohort; Quadruple Combination Cohorts; Triple Combination Cohorts

Hypofractionated radiotherapy RADIATION

Dual Combination Cohorts; Quadruple Combination Cohorts; Triple Combination Cohorts

Cyclophosphamide DRUG

Dual Combination Cohorts; Quadruple Combination Cohorts; Triple Combination Cohorts

Docetaxel DRUG

Dual Combination Cohorts; Triple Combination Cohorts

Carboplatin DRUG

Triple Combination Cohorts

GM-CSF DRUG

Also known as: LEUKINE®

Quadruple Combination Cohorts; Triple Combination Cohorts

Paclitaxel DRUG

Triple Combination Cohorts

Pemetrexed DRUG

Triple Combination Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (47)

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Location

Western Regional Medical Center

Goodyear, Arizona, United States

Location

Mayo Clinic

Phoenix, Arizona, United States

Location

University of Arizona Cancer Center

Tucson, Arizona, United States

Location

City of Hope National Medical Center

Duarte, California, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Location

Stanford University

Stanford, California, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Location

Norwalk Hospital

Norwalk, Connecticut, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Location

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Location

University of Chicago

Chicago, Illinois, United States

Location

Indiana University

Indianapolis, Indiana, United States

Location

University of Kansas Cancer Center

Fairway, Kansas, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Location

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, United States

Location

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Location

Columbia University Medical Center

New York, New York, United States

Location

Laura & Isaac Perlmutter Cancer Center

New York, New York, United States

Location

Mount Sinai Medical Center

New York, New York, United States

Location

Weill Cornell Medical College

New York, New York, United States

Location

Duke Cancer Institute

Durham, North Carolina, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Location

Providence Portland Medical Center

Portland, Oregon, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Location

University of Pittsburgh Medical Center Shadyside

Pittsburgh, Pennsylvania, 15232, United States

Location

Miriam Hospital

Providence, Rhode Island, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Location

Mary Crowley Cancer Research Center - Medical City

Dallas, Texas, United States

Location

Baylor College of Medicine

Houston, Texas, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Location

START South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States

Location

Northwest Medical Specialties

Tacoma, Washington, United States

Location

Peter Maccallum Cancer Centre

Melbourne, Australia

Location

Institut Catala d'Oncologia L'hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Fundacion Jimenez Diaz

Madrid, Spain

Location

Hospital Universitario HM Sanchinarro-CIOCC

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Spain

Location

MD Anderson Cancer Center

Madrid, Spain

Location

Related Publications (5)

• 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.

  PMID: 33942954 DERIVED

• 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.

  PMID: 33831732 DERIVED

• 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.

  PMID: 32554615 DERIVED

• 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.

  PMID: 29863979 DERIVED

• 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.

  PMID: 27879972 DERIVED

MeSH Terms

Interventions

cemiplimab; Radiation Dose Hypofractionation; Cyclophosphamide; Docetaxel; Carboplatin; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim; Paclitaxel; Pemetrexed

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Coordination Complexes; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2015
• First Posted: March 9, 2015
• Study Start: February 2, 2015
• Primary Completion: November 18, 2019
• Study Completion: November 18, 2019
• Last Updated: January 27, 2020

Record last verified: 2020-01

Locations

US (40); ES (6); AU (1)