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

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).

Primary Outcome Measures

1. DFS defined as time from randomization to the first documented disease recurrence (local, regional and/or distant); or death due to any cause.
   For patients who do not have a tumor recurrence or death, DFS will be censored on the date of last disease assessment.

Secondary Outcome Measures

1. 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.
2. 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.
   For patients who do not have a LRR or death, FFLRR will be censored on the date of last disease assessment.
3. 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.
   For patients who do not have a DR or death, FFDR will be censored on the date of last disease assessment.
4. 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.
5. Incidence and severity of treatment-emergent adverse events (TEAE)
6. Incidence of deaths
7. Incidence of laboratory abnormalities
8. Cemiplimab concentrations in serum
9. Anti-drug antibodies (ADA) in serum