A Study Comparing Cemiplimab-based Treatments for Adult Participants With Locally Advanced Basal Cell Skin Cancer (laBCC)

Phase 2 Platform Trial of Combination Therapies for Participants With Locally Advanced Basal Cell Carcinoma: Master Protocol With Cemiplimab Monotherapy as Comparator Arm

This study will test an experimental Regeneron drug called cemiplimab ("study drug") given alone or in combination with other anti-cancer drugs ("combination treatment") to see if they can help treat laBCC.

The study is looking at:

• What side effects cemiplimab, alone or in a combination treatment, might cause
• How well cemiplimab, alone or in a combination treatment, works
• How cemiplimab, alone or in a combination treatment could affect the immune system, which can help researchers understand why cemiplimab, alone or in a combination treatment, works better in some participants than others

Key Inclusion Criteria:

1. Histologic confirmation of BCC by local board-certified pathologist, as described in the protocol
2. At least one lesion that is measurable by study criteria, defined as ≥ 1cm in at least one dimension, as assessed by radiology and/or digital medical photography, as described in the protocol
3. The treating physician must document that the participant is not appropriate for curative-intent surgery or curative-intent radiation
4. The treating physician must document that the participant does not wish to receive a hedgehog pathway inhibitor (HHI) or is not a candidate for an HHI
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Subsequent Therapy Arm - specific inclusion criteria:

1. Documentation of histopathologic diagnosis of basal cell carcinoma - NOT necessary
2. Submission of tumor or blood for exploratory correlative research - NOT necessary

Key Exclusion Criteria:

1. Metastatic disease to lymph node(s) or distant site(s) (Note: involvement of lymph node due to direct invasion from overlying cutaneous BCC is still considered laBCC, and is not excluded)
2. History or current evidence of significant cardiovascular disease, as described in the protocol
3. Exposure to any prior systemic therapy (eg, HHI or an immune checkpoint inhibitor) or locally injectable agent for laBCC, as described in the protocol
4. Current participation OR past participation in another investigational trial in which an investigational intervention (eg, drug, vaccine, invasive device) was administered within 4 weeks before planned first dose of study intervention in this clinical trial.

Subsequent Therapy Arm - specific exclusion criteria:

1. Receipt of any anti-cancer therapy (including HHIs, radiation, surgery, or other systemic therapy) for BCC, AFTER treatment on Arms A, B, or C.

NOTE: Other protocol defined inclusion/exclusion criteria apply