Clinical trial NCT02383212: Study of REGN2810 (Anti-PD-1) in Patients With Advanced Malignancies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Advanced Malignancies
Keywords: Advanced cancerous growth
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2015-03-09
Enrollment: 398
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Change from baseline to week 48
measure: Incidence of abnormal laboratory findings
timeFrame: Change from baseline to week 48
measure: Number of participants with dose limiting toxicities (DLTs)
timeFrame: Change from baseline to 28 days after first dose of cemiplimab
Secondary outcomes:
measure: Response Evaluation Criteria in Solid Tumors (RECIST) as measured by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)
timeFrame: Change from baseline to week 48
measure: Immune-Related Response Criteria (irRC) applied to RECIST measurements
timeFrame: Change from baseline to week 48
measure: Incidence of development of anti-cemiplimab antibodies
timeFrame: Up to week 48
measure: Antitumor activity measured by progression-free survival (PFS)
timeFrame: Up to 72 weeks
measure: Antitumor activity measured by overall survival
timeFrame: Up to 249 weeks
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Goodyear
country: United States
facility: Western Regional Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Fairway
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine Siteman Cancer Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Shadyside
state: Pennsylvania
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center - Medical City
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: START South Texas Accelerated Research Therapeutics
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Catala d'Oncologia L'hospitalet
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro-CIOCC
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.