Abstract 1089TiP
Background
Basal cell carcinoma (BCC) is the most common skin cancer. Main drivers of BCC development are mutations in the hedgehog (HH) pathway, which allow proliferation of the malignant cells leading to tumor formation. Interestingly, despite carrying a high tumor mutational burden, BCC shows none or little immune infiltration and is considered an “immune-privileged” tumor. Most BCCs can be treated with local therapies, such as surgery, topical medications, cryo-, photodynamic or radiotherapy, but in advanced BCCs, systemic therapy is needed. HH pathway inhibitors (HHI) are small molecules, inhibiting the downstream signalling and eliciting anti-cancer effects. HHI cause clinical response in HH pathway-dependent tumours and are widely used in management of BCC. However, a subset of patients develops primary or secondary resistance, which leads to disease progression. HHI increase CD8+ T cell infiltration in BCC, indicating a change in immune susceptibility of the tumor. This suggests a synergistic effect of combination of HHI with an immunotherapeutic agent. We initiated a clinical trial to evaluate tumor response and induction of immune response in patients with advanced BCC treated with a combination of Cemiplimab (anti-PD1 antibody) and Sonidegib (hedgehog inhibitor).
Trial design
20 patients with advanced BCC will be included in this open label, non-randomized clinical trial. After a run-in phase with Sonidegib, patients will receive a combination therapy of Cemiplimab and pulsed dosing Sonidegib (2 weeks on 2 weeks off). Primary endpoint of the trial is best response at any time between treatment start and 26 weeks after the initiation of the treatment. Secondary endpoints are tumor response at 26 weeks, changes in histology and immunogenicity of the tumor and treatment safety. Response will be evaluated according to immune related response criteria (irRC). Safety will be assessed using CTCAE v5. Tumor immunogenicity will be assessed in patients with biopsy assessable tumors and will include cellular and molecular markers, including programmed cell death ligand 1, HLA I and II, and lymphocyte infiltration. Additionally, optional fine needle aspirations will be performed during each visit.
Clinical trial identification
NCT04679480.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Sanofi, SunPharma.
Disclosure
E. Ramelyte: Financial Interests, Personal and Institutional, Advisory Role, Intermittent, project focused Consulting & Research relationship: Amgen; Financial Interests, Personal and Institutional, Advisory Role, Intermittent, project focused Consulting & Research relationship: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role, Intermittent, project focused Consulting & Research relationship: Novartis; Financial Interests, Personal and Institutional, Advisory Role, Intermittent, project focused Consulting & Research relationship: Sanofi; Financial Interests, Personal and Institutional, Advisory Role, Intermittent, project focused Consulting & Research relationship: Sunpharma. J-T. Maul: Financial Interests, Personal, Advisory Role: AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, UCB; Financial Interests, Personal, Invited Speaker: AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, UCB; Financial Interests, Personal, Other, participated in clinical trials: AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, UCB. M.C. Nägeli: Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Advisory Role: Sunpharma. R. Dummer: Financial Interests, Personal and Institutional, Advisory Role: Novartis; Financial Interests, Personal and Institutional, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal and Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Advisory Role: Amgen; Financial Interests, Personal and Institutional, Advisory Role: Takeda; Financial Interests, Personal and Institutional, Advisory Role: Pierre Fabre; Financial Interests, Personal and Institutional, Advisory Role: Sunpharma; Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Advisory Role: Catalym; Financial Interests, Personal and Institutional, Advisory Role: Second Genome; Financial Interests, Personal and Institutional, Advisory Role: Regeneron; Financial Interests, Personal and Institutional, Advisory Role: Alligator; Financial Interests, Personal and Institutional, Advisory Role: T3 Pharma; Financial Interests, Personal and Institutional, Advisory Role: MaxiVAX SA; Financial Interests, Personal and Institutional, Advisory Role: touchIME. All other authors have declared no conflicts of interest.