Study of Cemiplimab Alone or in Combination With Fianlimab and/or Other Experimental Agents in Adult Participants With Peri-operative Stage III/IV Cutaneous Squamous Cell Carcinoma (CSCC)

Regeneron Pharmaceuticals

Overview

This study is researching an investigational drug called REGN2810, also known as cemiplimab, and when combined with another investigational drug called REGN3767, also known as fianlimab (each individually called a "study drug" or called "study drugs" when combined). The study is focused on a type of skin cancer known as cutaneous squamous cell carcinoma (CSCC). The aim of the study is to see if cemiplimab or cemiplimab in combination with fianlimab can eliminate or reduce the number of living cancer cells in tumor(s) if taken before surgery. The study is looking at several other research questions, including: * Whether taking cemiplimab or cemiplimab in combination with fianlimab before surgery may make it possible to have a less extensive surgery or a different treatment plan after surgery * Whether taking cemiplimab or cemiplimab in combination with fianlimab before surgery may make the cancer less likely to come back after surgery * What side effects may happen from taking the cemiplimab or cemiplimab in combination with fianlimab * How much of the cemiplimab or cemiplimab in combination with fianlimab is in the blood at different times * Whether the body makes antibodies against the study drug(s) (which could make the drug(s) less effective or could lead to side effects)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

Cutaneous Squamous Cell Carcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Stage III/IV (M0) CSCC, for which surgery would be recommended in routine clinical practice 2. Tumor biopsy is required during screening period as described in the protocol 3. Participant is willing to undergo delayed surgery 4. At least 1 lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Adequate organ and bone marrow function as described in the protocol Key Exclusion Criteria: 1. Stage I or II CSCC 2. Anogenital, penile, vermilion lip CSCC 3. CSCC bone invasion 4. Solid malignancy within 5 years of the projected enrollment date, or hematologic malignancy as described in the protocol 5. Prior radiation therapy for CSCC 6. Myocardial infarction within 6 months of enrollment, or history of myocarditis. 7. Prior treatment with anti-cancer systemic therapy within the last 3 years prior to projected enrollment date as described in the protocol Note: Other protocol-defined Inclusion/Exclusion Criteria apply

Outcomes

Primary Outcomes

Pathological complete response (pCR) rate by blinded independent pathological review (BIPR)

Time frame: Up to 100 days

Secondary Outcomes

pCR rate by local pathological review

Time frame: Up to 100 days

Major pathological response (MPR)

Time frame: Up to 100 days

Event-free survival (EFS)

Time frame: Up to 3 years

Disease free survival (DFS)

Time frame: Up to 3 years

Objective response rate (ORR) prior to surgery

Time frame: Up to 100 days

Overall survival (OS)

Time frame: Up to 3 years

Occurrence of treatment-emergent adverse events (TEAEs)

Time frame: Up to 3 years

Occurrence of immune-mediated adverse events (imAEs)

Time frame: Up to 3 years

Occurrence of treatment-related TEAEs

Time frame: Up to 3 years

Occurrence of adverse event of special interest (AESI)

Time frame: Up to 3 years

Occurrence of treatment-emergent serious adverse events (SAEs)

Time frame: Up to 3 years

Occurrence of laboratory abnormalities

Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0

Time frame: Up to 3 years

Occurrence of death due to TEAE

Time frame: Up to 3 years

Occurrence of interruption of study drug(s) due to TEAEs

Time frame: Up to 3 years

Occurrence of discontinuation of study drug(s) due to TEAEs

Time frame: Up to 3 years

Occurrence of cancellation of surgery due to TEAE

Time frame: Up to 100 days

Occurrence of delay to surgery due to TEAE

Time frame: Up to 100 days

Concentrations of cemiplimab in serum

Time frame: Up to 3 years

Concentrations of fianlimab in serum

Time frame: Up to 3 years

Concentrations of other experimental agents (as applicable) in serum

Time frame: Up to 3 years

Incidence of anti-drug antibodies (ADA) to cemiplimab

Time frame: Up to 3 years

Incidence of ADA to fianlimab

Time frame: Up to 3 years

Incidence of ADA to other experimental agents (as applicable)

Time frame: Up to 3 years

Titer of ADA to cemiplimab

Time frame: Up to 3 years

Titer of ADA to fianlimab

Time frame: Up to 3 years

Titer of ADA to other experimental agents (as applicable)

Time frame: Up to 3 years