Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma

• ClinicalTrials.gov Identifier: NCT02760498
• Recruitment Status: Completed
• First Posted: May 3, 2016
• Last Update Posted: December 13, 2023
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: April 8, 2016
• First Posted Date: May 3, 2016
• Last Update Posted Date: December 13, 2023
• Actual Study Start Date: April 7, 2016
• Actual Primary Completion Date: October 18, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 23, 2021)

Overall Response Rate (ORR) [ Time Frame: 30 months ]

Groups 1, 3, 4, and 6: Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 will be used to determine ORR. Group 2: Clinical response criteria will be used to determine ORR

Original Primary Outcome Measures (submitted: April 29, 2016)

Overall Response Rate [ Time Frame: During the 12 treatment cycles (96 weeks) ]

Overall Response Rate as determined by RECIST 1.1 for Group 1 and/or assessed per composite response criteria (Group 2)

Current Secondary Outcome Measures (submitted: December 23, 2021)

• Investigator Assessments of ORR [ Time Frame: Up to 30 months ]
  Groups 1-4, and 6
• Duration of response [ Time Frame: Up to 30 months ]
  Groups 1-4, and 6
• PFS (progression-free survival) [ Time Frame: Up to 30 months ]
  Groups 1-4, and 6
• Overall Survival [ Time Frame: Up to 30 months ]
  Groups 1-4, and 6
• Complete Response (CR) Rate [ Time Frame: Up to 30 months ]
  Groups 1-4, and 6
• Change in scores of patient reported outcomes on EORTC QLQ-C30 [ Time Frame: Up to 30 months ]
  Except Group 6
• Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 months ]
• Cemiplimab PK: Concentration at end-of-infusion (Ceoi) (IV) [ Time Frame: Up to 24 months ]
• Cemiplimab PK: Peak concentrations (Cmax) (SC) [ Time Frame: Up to 24 months ]
• Cemiplimab PK: Pre-infusion concentration (Ctrough) [ Time Frame: Up to 24 months ]
• Cemiplimab PK: Time of end-of-infusion (teoi) [ Time Frame: Up to 24 months ]
• Cemiplimab PK: Time to peak concentration (tmax) (SC) [ Time Frame: Up to 24 months ]
• Cemiplimab PK: Area under the plasma concentration-time curve after the first SC or IV dose [ Time Frame: Up to 24 months ]
• Cemiplimab PK: Absolute bioavailability after SC administration [ Time Frame: Up to 24 months ]
• Anti-cemiplimab antibodies [ Time Frame: Up to 30 months ]
• Immunohistochemistry (IHC) assessment of correlation between PD-L1 status and ORR [ Time Frame: Up to 30 months ]
  Group 6
• IHC assessment of correlation between PD-L1 and DOR [ Time Frame: Up to 30 months ]
  Group 6
• IHC assessment of correlation between PD-L1 and PFS [ Time Frame: Up to 30 months ]
  Group 6

Original Secondary Outcome Measures (submitted: April 29, 2016)

• Duration of response [ Time Frame: From date of treatment until date of first documented progression or date of death, assessed up to 30 months ]
• PFS (progression-free survival) [ Time Frame: From date of treatment until date of death, assessed up to 30 months ]
• Overall Survival [ Time Frame: From date of treatment until date of death, assessed up to 30 months ]
• Change in scores of patient reported outcomes on EORTC QLQ-C30 [ Time Frame: From date of treatment until date of first documented progression or date of death, assessed up to 24 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma
• Official Title: A Phase 2 Study of REGN2810, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients With Advanced Cutaneous Squamous Cell Carcinoma

Brief Summary

Groups 1 to 4 To estimate the clinical benefit of cemiplimab monotherapy for patients with: metastatic (nodal or distant) cutaneous squamous cell carcinoma (CSCC), or unresectable locally advanced CSCC

Group 6 To provide additional efficacy and safety data for cemiplimab monotherapy in patients with advanced CSCC (metastatic [nodal or distant] or locally advanced treated with cemiplimab

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Cutaneous Squamous Cell Carcinoma

Intervention

Drug: cemiplimab

Other Names:

• REGN2810
• Libtayo

Study Arms

• Experimental: Group 1
  Patients with metastatic CSCC: to distant sites or lymph nodes. Cemiplimab administered intravenously (IV) every 2 weeks (Q2W).
  Intervention: Drug: cemiplimab
• Experimental: Group 2
  Patients with unresectable locally advanced CSCC. Cemiplimab administered IV Q2 weeks.
  Intervention: Drug: cemiplimab
• Experimental: Group 3
  Patients with metastatic CSCC to distant sites or lymph nodes. Cemiplimab administered IV Q3 weeks.
  Intervention: Drug: cemiplimab
• Experimental: Group 4
  Patients with advanced CSCC [metastatic (nodal or distal) or unresectable locally advanced] Cemplimab administered IV Q4 weeks.
  Intervention: Drug: cemiplimab
• Experimental: Group 6
  Patients with advanced CSCC (metastatic [nodal or distant] or locally advanced) who received cemiplimab IV Q3W for at least 27 weeks without experiencing disease progression, will have the option to receive cemiplimab by subcutaneous (SC) injection Q3W (first 12 patients) or Q6W (next ≥ 6 patients) basis.
  Intervention: Drug: cemiplimab

Publications *

• Rischin D, Khushalani NI, Schmults CD, Guminski A, Chang ALS, Lewis KD, Lim AM, Hernandez-Aya L, Hughes BGM, Schadendorf D, Hauschild A, Thai AA, Stankevich E, Booth J, Yoo SY, Li S, Chen Z, Okoye E, Chen CI, Mastey V, Sasane M, Lowy I, Fury MG, Migden MR. Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis. J Immunother Cancer. 2021 Aug;9(8):e002757. doi: 10.1136/jitc-2021-002757.
• Paccaly AJ, Migden MR, Papadopoulos KP, Yang F, Davis JD, Rippley RK, Lowy I, Fury MG, Stankevich E, Rischin D. Fixed Dose of Cemiplimab in Patients with Advanced Malignancies Based on Population Pharmacokinetic Analysis. Adv Ther. 2021 May;38(5):2365-2378. doi: 10.1007/s12325-021-01638-5. Epub 2021 Mar 25.
• 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, Khushalani NI, Chang ALS, Lewis KD, Schmults CD, Hernandez-Aya L, Meier F, Schadendorf D, Guminski A, Hauschild A, Wong DJ, Daniels GA, Berking C, Jankovic V, Stankevich E, Booth J, Li S, Weinreich DM, Yancopoulos GD, Lowy I, Fury MG, Rischin D. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol. 2020 Feb;21(2):294-305. doi: 10.1016/S1470-2045(19)30728-4. Epub 2020 Jan 14.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 23, 2021): 432
• Original Estimated Enrollment (submitted: April 29, 2016): 129
• Actual Study Completion Date: October 18, 2023
• Actual Primary Completion Date: October 18, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• At least 1 measurable lesion
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Adequate bone marrow function
• Adequate renal function
• Adequate hepatic function
• Archived or newly obtained tumor material
• Patients must consent to undergo biopsies of CSCC lesions (Groups 2, 4, and 6)
• Surgical or radiological treatment of lesions contraindicated

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
• Prior treatment with an agent that blocks the PD-1/PD-L1pathway
• Prior treatment with a BRAF inhibitor
• Prior treatment with other immune-modulating agents within fewer than 4 weeks prior to the first dose of cemiplimab, or associated with immune-mediated adverse events that were ≥ grade 1 within 90 days prior to the first dose of cemiplimab, or associated with toxicity that resulted in discontinuation of the immune-modulating agent. Examples of immune-modulating agents include therapeutic vaccines, cytokine treatments, or agents that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), 4-1BB (CD137), or OX-40.
• Untreated brain metastasis(es) that may be considered active
• Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab
• Infection with human immunodeficiency virus (HIV) and/or chronic/active infection with hepatitis B virus or hepatitis C virus
• History of non-infectious pneumonitis within the last 5 years
• Allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
• Known allergy to doxycycline or tetracycline
• Patients with a history of solid organ transplant
• Any medical co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that renders the patient unsuitable

Other protocol-defined inclusion/exclusion criteria apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, France, Germany, Greece, Italy, Spain, United States
• Removed Location Countries: New Zealand

Administrative Information

• NCT Number: NCT02760498
• Other Study ID Numbers: R2810-ONC-1540; 2016-000105-36 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: December 2023