Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma

• ClinicalTrials.gov Identifier: NCT03969004
• Recruitment Status: Active, not recruiting
• First Posted: May 31, 2019
• Last Update Posted: February 8, 2021
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: May 6, 2019
• First Posted Date: May 31, 2019
• Last Update Posted Date: February 8, 2021
• Actual Study Start Date: June 4, 2019
• Estimated Primary Completion Date: October 16, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 28, 2019)

DFS defined as time from randomization to the first documented disease recurrence (local, regional and/or distant); or death due to any cause. [ Time Frame: Up to 54 months ]

For patients who do not have a tumor recurrence or death, DFS will be censored on the date of last disease assessment.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 28, 2019)

• Overall survival (OS), defined as time from randomization to the date of death. A patient who has not died will be censored on the last known date as alive. [ Time Frame: Up to 78 months ]
• FFLRR defined as time from randomization to the date of first locoregional recurrence (LRR). Patients who died without a preceding LRR will be censored on the date of death. [ Time Frame: Up to 54 months ]
  For patients who do not have a LRR or death, FFLRR will be censored on the date of last disease assessment.
• Freedom from distant recurrence (FFDR), defined as time from randomization to the date of first distant recurrence (DR). Patients who died without a preceding DR will be censored on the date of death. [ Time Frame: Up to 54 months ]
  For patients who do not have a DR or death, FFDR will be censored on the date of last disease assessment.
• Cumulative occurrence of second primary cutaneous squamous cell carcinoma tumor (SPTs) for each patient from randomization to occurrence of first primary endpoint event or end of study. [ Time Frame: Up to 54 months ]
• Incidence and severity of treatment-emergent adverse events (TEAE) [ Time Frame: Up to 78 months ]
• Incidence of deaths [ Time Frame: Up to 78 months ]
• Incidence of laboratory abnormalities [ Time Frame: Up to 78 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma
• Official Title: A Randomized, Placebo-Controlled, Double-Blind Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma

Brief Summary

The primary objective of the study is to compare disease-free survival (DFS) of patients with high-risk cutaneous squamous cell carcinoma (CSCC) treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and radiation therapy (RT).

The secondary objectives of the study are:

• To compare the overall survival (OS) of high-risk CSCC patients treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and RT
• To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from locoregional recurrence (FFLRR) after surgery and RT
• To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from distant recurrence (FFDR) after surgery and RT
• To compare the effect of adjuvant cemiplimab with that of placebo on the cumulative incidence of second primary CSCC tumors (SPTs) after surgery and RT
• To evaluate the safety of adjuvant cemiplimab and that of placebo in high-risk CSCC patients after surgery and RT

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cutaneous Squamous Cell Carcinoma

Intervention

• Drug: Cemiplimab
  Intravenous (IV) infusion over 30 minutes
  Other Names:

  • REGN2810
  • Libtayo
• Drug: Placebo
  Intravenous (IV) infusion over 30 minutes

Study Arms

• Experimental: Cemiplimab
  Intervention: Drug: Cemiplimab
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 5, 2021): 75
• Original Estimated Enrollment (submitted: May 28, 2019): 412
• Estimated Study Completion Date: February 11, 2026
• Estimated Primary Completion Date: October 16, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• For Japan only, men and women ≥21 years old
• Patient with resection of pathologically confirmed CSCC (primary CSCC lesion only, or primary CSCC with nodal involvement, or CSCC nodal metastasis with known primary CSCC lesion previously treated within the draining lymph node echelon), with macroscopic gross resection of all disease
• High risk CSCC, as defined in the protocol
• Completion of curative intent post-operative radiation therapy (RT) within 2 to 6 weeks of randomization
• Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1
• Adequate hepatic, renal, and bone marrow function as defined in the protocol

Key Exclusion Criteria:

• Squamous cell carcinomas (SCCs) arising in non-cutaneous sites as defined in the protocol
• Concurrent malignancy other than localized CSCC and/or history of malignancy other than localized CSCC within 3 years of date of randomization as defined in the protocol
• Patients with hematologic malignancies (eg, chronic lymphocytic leukemia (CLL))
• Patients with history of distantly metastatic CSCC (visceral or distant nodal), unless the disease-free interval is at least 3 years (regional nodal involvement of disease in draining lymph node basin that was resected and radiated prior to enrollment will not be exclusionary)
• Ongoing or recent (within 5 years of randomization date) 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, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
• Has had prior systemic anti-cancer immunotherapy for CSCC

Note: 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, Belgium, Brazil, Canada, France, Germany, Greece, Ireland, Italy, Japan, New Zealand, Poland, Russian Federation, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03969004
• Other Study ID Numbers: R2810-ONC-1788; 2019-000566-38 ( 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

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency [EMA], Pharmaceuticals and Medical Devices Agency [PMDA], etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• URL: https://vivli.org/

• Responsible Party: Regeneron Pharmaceuticals
• Study Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: April 2020