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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02383212




Registration number
NCT02383212
Ethics application status
Date submitted
2/02/2015
Date registered
9/03/2015
Date last updated
27/01/2020

Titles & IDs
Public title
Study of REGN2810 (Anti-PD-1) in Patients With Advanced Malignancies
Scientific 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
Secondary ID [1] 0 0
2015-002132-41
Secondary ID [2] 0 0
R2810-ONC-1423
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Advanced Malignancies 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Monotherapy Cohort - Cemiplimab will be administered alone

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

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

Experimental: Quadruple Combination Cohorts - Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF plus Cyclophosphamide
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Treatment Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Change from baseline to week 48
Primary outcome [2] 0 0
Incidence of abnormal laboratory findings
Timepoint [2] 0 0
Change from baseline to week 48
Primary outcome [3] 0 0
Number of participants with dose limiting toxicities (DLTs)
Timepoint [3] 0 0
Change from baseline to 28 days after first dose of cemiplimab
Secondary outcome [1] 0 0
Response Evaluation Criteria in Solid Tumors (RECIST) as measured by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)
Timepoint [1] 0 0
Change from baseline to week 48
Secondary outcome [2] 0 0
Immune-Related Response Criteria (irRC) applied to RECIST measurements
Timepoint [2] 0 0
Change from baseline to week 48
Secondary outcome [3] 0 0
Incidence of development of anti-cemiplimab antibodies
Timepoint [3] 0 0
Up to week 48
Secondary outcome [4] 0 0
Antitumor activity measured by progression-free survival (PFS)
Timepoint [4] 0 0
Up to 72 weeks
Secondary outcome [5] 0 0
Antitumor activity measured by overall survival
Timepoint [5] 0 0
Up to 249 weeks

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/02/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/11/2019
Sample size
Target
Accrual to date
Final
398
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
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California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
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United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
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Georgia
Country [8] 0 0
United States of America
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Illinois
Country [9] 0 0
United States of America
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Indiana
Country [10] 0 0
United States of America
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Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
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Missouri
Country [14] 0 0
United States of America
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Nebraska
Country [15] 0 0
United States of America
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New Jersey
Country [16] 0 0
United States of America
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New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
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Oklahoma
Country [20] 0 0
United States of America
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Oregon
Country [21] 0 0
United States of America
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Pennsylvania
Country [22] 0 0
United States of America
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Rhode Island
Country [23] 0 0
United States of America
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Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
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Washington
Country [26] 0 0
Spain
State/province [26] 0 0
Barcelona
Country [27] 0 0
Spain
State/province [27] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Regeneron Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Sanofi
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02383212
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02383212