LBA47 - Primary analysis of phase II results for cemiplimab in patients (pts) with locally advanced basal cell carcinoma (laBCC) who progress on or are intolerant to hedgehog inhibitors (HHIs)

Background

There is no approved therapeutic option post-HHI for pts with laBCC. Cemiplimab, an antibody to PD-1, is an established therapy approved for treatment of advanced cutaneous squamous cell carcinoma (CSCC) in pts who are not candidates for curative surgery or curative radiation. Both BCC and CSCC are keratinocytic tumours with high mutational burden due to ultraviolet mutagenesis and are potentially amenable to immunotherapy. We present the primary analysis of the laBCC cohort from the pivotal phase II study of cemiplimab in the second-line (or greater) setting.

Methods

Pts with laBCC received cemiplimab 350 mg Q3W IV (for up to 93 weeks or until progression). The primary endpoint was objective response rate (ORR) by Independent Central Review (ICR). Secondary objectives included assessment of safety and tolerability, estimation of duration of response (DOR), progression-free survival (PFS) and overall survival (OS). ORR included two responses confirmed after the data cut-off date of 17 February 2020.

Results

84 pts were enrolled; 66.7% male; median age was 70 years (range: 42−89). Median follow-up was 15 months (range: 0.5−25). ORR per ICR was 31% (95% CI: 21−42), including five complete responses and 21 partial responses. Median DOR has not been reached; an estimated 85% of responses were ongoing at 12 months, per the Kaplan–Meier method. Median PFS and OS had not been reached. Estimated PFS for all patients was 19 months. The most common adverse events (AEs) were fatigue (30%), diarrhoea (24%) and pruritus (21%); 17% of patients discontinued treatment due to AEs. Median baseline tumour mutational burden (TMB) was 58.2 and 23.5 mutations/Mb among responding (n=18) and non-responding (n=38) pts, respectively, but responses occurred at all TMB levels. Exploratory biomarker analysis identified downregulation of major histocompatibility complex-I expression as a potential immune evasion mechanism in non-responding BCCs with high TMB.

Conclusions

Cemiplimab is the first agent to establish clinical benefit for pts with laBCC who progress on or are intolerant to HHI therapy, regardless of biomarker status.

Clinical trial identification

NCT03132636.

Editorial acknowledgement

Medical writing support was provided by Cindi Hoover, PhD of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc. and Sanofi.

Funding

Regeneron Pharmaceuticals, Inc. and Sanofi.

Disclosure

A.J. Stratigos: Advisory/Consultancy: Janssen Cilag; Advisory/Consultancy: Regeneron Pharmaceuticals, Inc.; Advisory/Consultancy: Sanofi; Research grant/Funding (self): AbbVie; Research grant/Funding (self): BMS; Research grant/Funding (self): Genesis Pharma; Research grant/Funding (self): Novartis. A. Sekulic: Advisory/Consultancy: Regeneron Pharmaceuticals, Inc ; Advisory/Consultancy: Roche. K. Peris: Advisory/Consultancy, outside the submitted work: AbbVie; Advisory/Consultancy, outside the submitted work: Leo Pharma; Advisory/Consultancy, outside the submitted work: Janssen; Advisory/Consultancy, outside the submitted work: Almirall; Advisory/Consultancy, outside the submitted work: Lilly; Advisory/Consultancy, outside the submitted work: Galderma; Advisory/Consultancy, outside the submitted work: Novartis; Advisory/Consultancy, outside the submitted work: Pierre Fabre; Advisory/Consultancy, outside the submitted work: Sanofi. O. Bechter: Advisory/Consultancy: Novartis; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Ultimovacs. K.D. Lewis: Research grant/Funding (self): University of Colorado; Research grant/Funding (self), Grants and personal fees: Regeneron Pharmaceuticals, Inc. N. Basset-Seguin: Full/Part-time employment: Sun Pharmaceutical Industries, Inc.; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Galderma; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Leo; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Licensing/Royalties, Patents, royalties, or other intellectual property: Genentech/F. Hoffmann-La Roche, Ltd. A.L.S. Chang: Advisory/Consultancy, Research grant/Funding (self): Regeneron Pharmaceuticals, Inc.; Advisory/Consultancy, Research grant/Funding (self): Merck; Research grant/Funding (self): Novartis; Research grant/Funding (self): Galderma. S. Dalle: Spouse/Financial dependant, Spouse is an employee of Sanofi: Sanofi. L. Licitra: Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: Eisai; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: Merck Serono; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: MSD; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Debiopharm; Advisory/Consultancy: Sobi; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Medpace; Research grant/Funding (institution): IRX Therapeutics; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Incyte Biosciences; Advisory/Consultancy: Doxa Pharma; Advisory/Consultancy: Amgen; Advisory/Consultancy: Nanobiotics SA; Advisory/Consultancy: GlaxoSmithKline; Speaker Bureau/Expert testimony: AccMed; Speaker Bureau/Expert testimony: Medical Science Fundation G. Lorenzini; Speaker Bureau/Expert testimony: Associazione Sinapsi; Speaker Bureau/Expert testimony: Think 2 IT; Speaker Bureau/Expert testimony: Aiom Servizi; Speaker Bureau/Expert testimony: Prime Oncology; Speaker Bureau/Expert testimony: WMA Congress Education; Speaker Bureau/Expert testimony: Fasi, DueCi promotion Srl, MI&T, Net Congress & Education, PRMA Consulting, Kura Oncology, Health & Life srl, Immuno-Oncology Hub. C. Robert: Advisory/Consultancy: BMS; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Merck; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Biothera; Advisory/Consultancy: Ultimovacs. C. Ulrich: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Regeneron Pharmaceuticals, Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sun Pharma. A. Hauschild: Research grant/Funding (institution), and personal fees: Amgen; Research grant/Funding (institution), And personal fees: BMS; Research grant/Funding (institution), and personal fees: MerckSerono; Research grant/Funding (institution), and personal fees: MSD/Merck; Research grant/Funding (institution), and personal fees: Philogen; Research grant/Funding (institution), and personal fees: Pierre Fabre; Research grant/Funding (institution), and personal fees: Provectus; Research grant/Funding (institution), and personal fees: Regeneron Pharmaceuticals, Inc.; Research grant/Funding (institution), and personal fees: Roche; Research grant/Funding (institution), and personal fees: Sanofi-Genzyme; Research grant/Funding (institution), and personal fees: Novartis; Advisory/Consultancy: OncoSec; Advisory/Consultancy: Sun Pharma. M.R. Migden: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Regeneron Pharmaceuticals, Inc.; Advisory/Consultancy, Travel/Accommodation/Expenses: Sun Pharmaceuticals; Advisory/Consultancy: Rakuten Medical; Research grant/Funding (self): Pelle Pharm. R. Dummer: Advisory/Consultancy, outside the submitted work: Novartis; Advisory/Consultancy, outside the submitted work: Merck Sharp & Dhome; Advisory/Consultancy, outside the submitted work: Bristol-Myers Squibb; Advisory/Consultancy, outside the submitted work: Roche; Advisory/Consultancy, outside the submitted work: Amgen; Advisory/Consultancy, outside the submitted work: Takeda; Advisory/Consultancy, outside the submitted work: Pierre Fabre; Advisory/Consultancy, outside the submitted work: Sun Pharma; Advisory/Consultancy, outside the submitted work: Sanofi; Advisory/Consultancy, outside the submitted work: Catalym; Advisory/Consultancy, outside the submitted work: Second Genome; Advisory/Consultancy, outside the submitted work: Regeneron Pharmaceuticals, Inc.; Advisory/Consultancy, outside the submitted work: Alligator. S. Li: Shareholder/Stockholder/Stock options, Full/Part-time employment: Regeneron Pharmaceuticals, Inc. T. Bowler: Shareholder/Stockholder/Stock options, Full/Part-time employment: Regeneron Pharmaceuticals, Inc. M.G. Fury: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Patent holder: of Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.