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: Recruiting
• First Posted: May 31, 2019
• Last Update Posted: July 22, 2022
• 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: July 22, 2022
• Actual Study Start Date: June 4, 2019
• Estimated Primary Completion Date: December 19, 2025 (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: January 27, 2022)

• 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 ]
• Cemiplimab concentrations in serum [ Time Frame: Up to 78 months ]
• Anti-drug antibodies (ADA) in serum [ Time Frame: Up to 78 months ]

Original 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 ]

• 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
• To assess cemiplimab pharmacokinetics and immunogenicity in human serum

Detailed Description

Cemiplimab is a monoclonal antibody. Antibodies are proteins naturally found in the blood. A monoclonal antibody is a special antibody that is manufactured as a medication to target specific proteins in the body that may be involved in cancer. Cemiplimab works by blocking programmed death-1 (PD-1), a cell receptor on immune cells. By blocking PD-1, it is expected that the immune cells will attack cancer cells.

The study is being conducted in participants that have had surgery and radiation therapy for a type of skin cancer called cutaneous squamous cell cancer, and who have a risk that this cancer may come back.

The main purpose of the study is to determine if cemiplimab will prevent cutaneous squamous cell cancer (CSCC) from returning after surgery and radiation. Currently, we know that certain types of CSCC have a high chance of coming back after surgery and radiation. At this time, there is no approved treatment to give patients after surgery and radiation to prevent high-risk CSCC from coming back. We are investigating if the addition of cemiplimab will decrease the chance of these high-risk cancers coming back.

The study will also investigate if cemiplimab may help participants live for longer.

The study has two parts. Part 1: participants will receive every 3 weeks via intravenous infusion (drip into a vein) either cemiplimab (study drug) or placebo (similar to the study drug but without active medicine). After 12 weeks of treatment, cemiplimab or placebo will be given every 6 weeks. Part 1 of the study includes a screening period (up to 28 days), a treatment period (approximately 48 weeks), an end of treatment visit (approximately 30 days after completion of study drug treatment period) and a post-treatment follow-up period (approximately up to 5 years or until skin cancer returns or the study ends).

Part 2 of the study is optional and provides the participant with the option to receive cemiplimab if the cancer comes back if the participant was initially receiving placebo. There is no placebo in Part 2 of the study. If the cancer comes back, the study doctor will discuss with participants if they are eligible to participate in the optional part 2 of the study.

Part 2 of the study includes a brief screening period, a treatment period (approximately 96 weeks) and an end of treatment visit (approximately 30 days after the completion of the study drug treatment period).

• 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: Recruiting
• Estimated Enrollment (submitted: May 28, 2019): 412
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 28, 2027
• Estimated Primary Completion Date: December 19, 2025 (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 10 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 (note: patients with chronic lymphocytic leukemia (CLL) are not excluded if they have not required systemic therapy for CLL within 6 months of enrollment)
• 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: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

• 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/

• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: July 2022