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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02760498




Registration number
NCT02760498
Ethics application status
Date submitted
8/04/2016
Date registered
3/05/2016
Date last updated
13/12/2023

Titles & IDs
Public title
Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma
Scientific 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
Secondary ID [1] 0 0
2016-000105-36
Secondary ID [2] 0 0
R2810-ONC-1540
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cutaneous Squamous Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Group 1 - Patients with metastatic CSCC: to distant sites or lymph nodes. Cemiplimab administered intravenously (IV) every 2 weeks (Q2W).

Experimental: Group 2 - Patients with unresectable locally advanced CSCC. Cemiplimab administered IV Q2 weeks.

Experimental: Group 3 - Patients with metastatic CSCC to distant sites or lymph nodes. Cemiplimab administered IV Q3 weeks.

Experimental: Group 4 - Patients with advanced CSCC \[metastatic (nodal or distal) or unresectable locally advanced\] Cemplimab administered IV Q4 weeks.

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.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
30 months
Secondary outcome [1] 0 0
Investigator Assessments of ORR
Timepoint [1] 0 0
Up to 30 months
Secondary outcome [2] 0 0
Duration of response
Timepoint [2] 0 0
Up to 30 months
Secondary outcome [3] 0 0
PFS (progression-free survival)
Timepoint [3] 0 0
Up to 30 months
Secondary outcome [4] 0 0
Overall Survival
Timepoint [4] 0 0
Up to 30 months
Secondary outcome [5] 0 0
Complete Response (CR) Rate
Timepoint [5] 0 0
Up to 30 months
Secondary outcome [6] 0 0
Change in scores of patient reported outcomes on EORTC QLQ-C30
Timepoint [6] 0 0
Up to 30 months
Secondary outcome [7] 0 0
Incidence of Treatment Emergent Adverse Events (TEAEs)
Timepoint [7] 0 0
Up to 30 months
Secondary outcome [8] 0 0
Cemiplimab PK: Concentration at end-of-infusion (Ceoi) (IV)
Timepoint [8] 0 0
Up to 24 months
Secondary outcome [9] 0 0
Cemiplimab PK: Peak concentrations (Cmax) (SC)
Timepoint [9] 0 0
Up to 24 months
Secondary outcome [10] 0 0
Cemiplimab PK: Pre-infusion concentration (Ctrough)
Timepoint [10] 0 0
Up to 24 months
Secondary outcome [11] 0 0
Cemiplimab PK: Time of end-of-infusion (teoi)
Timepoint [11] 0 0
Up to 24 months
Secondary outcome [12] 0 0
Cemiplimab PK: Time to peak concentration (tmax) (SC)
Timepoint [12] 0 0
Up to 24 months
Secondary outcome [13] 0 0
Cemiplimab PK: Area under the plasma concentration-time curve after the first SC or IV dose
Timepoint [13] 0 0
Up to 24 months
Secondary outcome [14] 0 0
Cemiplimab PK: Absolute bioavailability after SC administration
Timepoint [14] 0 0
Up to 24 months
Secondary outcome [15] 0 0
Anti-cemiplimab antibodies
Timepoint [15] 0 0
Up to 30 months
Secondary outcome [16] 0 0
Immunohistochemistry (IHC) assessment of correlation between PD-L1 status and ORR
Timepoint [16] 0 0
Up to 30 months
Secondary outcome [17] 0 0
IHC assessment of correlation between PD-L1 and DOR
Timepoint [17] 0 0
Up to 30 months
Secondary outcome [18] 0 0
IHC assessment of correlation between PD-L1 and PFS
Timepoint [18] 0 0
Up to 30 months

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

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 2
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
7/04/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/10/2023
Sample size
Target
Accrual to date
Final
432
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Gosford Hospital - Gosford
Recruitment hospital [3] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [5] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [7] 0 0
Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [8] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [9] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [10] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
- Garran
Recruitment postcode(s) [2] 0 0
- Gosford
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
- Waratah
Recruitment postcode(s) [5] 0 0
4029 - Herston
Recruitment postcode(s) [6] 0 0
- Woolloongabba
Recruitment postcode(s) [7] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [8] 0 0
3000 - Melbourne
Recruitment postcode(s) [9] 0 0
- Wodonga
Recruitment postcode(s) [10] 0 0
6009 - Nedlands
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
State/province [2] 0 0
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
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
Brazil
State/province [17] 0 0
Rio Grande Do Sul
Country [18] 0 0
Brazil
State/province [18] 0 0
Curitiba
Country [19] 0 0
Brazil
State/province [19] 0 0
Ipatinga
Country [20] 0 0
Brazil
State/province [20] 0 0
Lages
Country [21] 0 0
Brazil
State/province [21] 0 0
Sao Paulo
Country [22] 0 0
Brazil
State/province [22] 0 0
São Paulo
Country [23] 0 0
France
State/province [23] 0 0
Nord
Country [24] 0 0
France
State/province [24] 0 0
Bobigny
Country [25] 0 0
France
State/province [25] 0 0
Bordeaux
Country [26] 0 0
France
State/province [26] 0 0
Dijon
Country [27] 0 0
France
State/province [27] 0 0
Grenoble
Country [28] 0 0
France
State/province [28] 0 0
Marseille
Country [29] 0 0
France
State/province [29] 0 0
Nantes
Country [30] 0 0
France
State/province [30] 0 0
Paris
Country [31] 0 0
France
State/province [31] 0 0
Pierre Bénite
Country [32] 0 0
France
State/province [32] 0 0
Villejuif
Country [33] 0 0
Germany
State/province [33] 0 0
Baden-Württemberg
Country [34] 0 0
Germany
State/province [34] 0 0
Bayern
Country [35] 0 0
Germany
State/province [35] 0 0
Niedersachsen
Country [36] 0 0
Germany
State/province [36] 0 0
Nordrhein-Westfalen
Country [37] 0 0
Germany
State/province [37] 0 0
Sachsen
Country [38] 0 0
Germany
State/province [38] 0 0
Schleswig-Holstein
Country [39] 0 0
Germany
State/province [39] 0 0
Berlin
Country [40] 0 0
Germany
State/province [40] 0 0
Gera
Country [41] 0 0
Greece
State/province [41] 0 0
Athens
Country [42] 0 0
Italy
State/province [42] 0 0
Campania
Country [43] 0 0
Italy
State/province [43] 0 0
Veneto
Country [44] 0 0
Italy
State/province [44] 0 0
Brescia
Country [45] 0 0
Italy
State/province [45] 0 0
L'Aquila
Country [46] 0 0
Italy
State/province [46] 0 0
Milan
Country [47] 0 0
Italy
State/province [47] 0 0
Roma
Country [48] 0 0
Spain
State/province [48] 0 0
Barelona
Country [49] 0 0
Spain
State/province [49] 0 0
Cataluna
Country [50] 0 0
Spain
State/province [50] 0 0
Barcelona
Country [51] 0 0
Spain
State/province [51] 0 0
Cordoba
Country [52] 0 0
Spain
State/province [52] 0 0
Madrid
Country [53] 0 0
Spain
State/province [53] 0 0
Santander
Country [54] 0 0
Spain
State/province [54] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Regeneron Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT02760498
Trial related presentations / 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.
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/NCT02760498