The FDA has now approved cemiplimab-rwlc (Libtayo®, Regeneron Pharmaceuticals) for patients with locally advanced or metastatic basal cell carcinoma (BCC) who received prior treatment with a hedgehog pathway inhibitor (HHI) and those who are ineligible for HHI therapy. Cemiplimab is the first immunotherapy to be approved for patients with advanced BCC.
"Cemiplimab, an antibody to programmed cell death protein 1 (PD-1), is an established therapy approved for treatment of advanced cutaneous squamous cell carcinoma (CSCC) in patients who are not candidates for curative surgery or radiation," wrote Alexander Stratigos, MD, Professor of Dermatology at the University of Athens Medical School, and colleagues in their abstract of results from Study 1620 (NCT03132636), presented at the European Society for Medical Oncology Congress in September 2020. "Both BCC and CSCC are keratinocytic tumors with high mutational burden due to ultraviolet malignancies and are potentially amenable to immunotherapy."
Study 1620, the open-label non-randomized phase 2 trial on which the approval was based, enrolled 84 patients with locally advanced BCC and 28 patients with nodal or distant metastatic BCC who were intolerant of HHI therapy, who had not experienced an objective response after nine months of treatment with an HHI, or whose disease had progressed following HHI therapy. Patients received 350 mg of cemiplimab every three weeks until disease progression, unacceptable toxicity, or completion of treatment, for a maximum of 93 weeks. The primary end point was objective response, with secondary end points of duration of response, progression-free survival, overall survival, and safety and tolerability.
In patients with locally advanced BCC, cemiplimab produced an objective response rate of 31%, including a complete response in 5 patients (17%). The median duration of response was not reached, with 85% of patients experiencing a response lasting at least 12 months. Median progression-free survival and overall survival were not reached, with an estimated progression-free survival of 19 months. Among patients with metastatic BCC, cemiplimab produced an objective response rate of 21%, with a median time to response of 3.2 months. All responders experienced a response lasting at least 8 months, with the median duration of response not yet reached. Estimated median progression-free survival and overall survival were 8.3 months and 25.7 months, respectively.
Adverse events occurring in at least 20% of patients included fatigue, musculoskeletal pain, diarrhea, rash, and pruritus. Severe immune-mediated adverse events included pneumonitis, hepatitis, colitis, adrenal insufficiency, hypothyroidism, hyperthyroidism, diabetes mellitus, and nephritis. Infusion-related reactions may also occur.
"Cemiplimab is the first agent to provide clinically meaningful antitumor activity, including durable responses, in patients with metastatic BCC after progression or intolerance on HHI therapy," wrote Karl Lewis, MD, Associate Professor of Medical Oncology at the University of Colorado School of Medicine, and colleagues in their presentation of results for the metastatic disease cohort at the Society for Immunotherapy of Cancer Annual Meeting in November 2020.
The recommended dose of cemiplimab is 350 mg administered as an intravenous infusion over 30 minutes once every three weeks.
For More Information
Stratigos AJ, Sekulic A, Peris K, et al (2020). 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). Ann Oncol (ESMO Virtual Congress Abstracts), 31(suppl_4):S1142-S1215. Abstract LBA47. DOI:10.1016/annonc/annonc325
Lewis K, Peris K, Sekulic A, et al (2020). Interim analysis of phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma (mBCC) who progressed on or are intolerant to hedgehog inhibitors (HHIs). J Immunother Cancer (Society for Immunotherapy of Cancer Annual Meeting Abstracts), 8(suppl_3). Abstract 428. DOI:10.1136/jitc-2020-SITC2020.0428
Clinicaltrials.gov (2020). PD-1 in patients with advanced basal cell carcinoma who experienced progression of disease on hedgehog pathway inhibitor therapy, or were intolerant of prior hedgehog inhibitor therapy. NLM identifier: NCT03132636.
US Food & Drug Administration (2021). FDA approves cemiplimab-rwlc for locally advanced and metastatic basal cell carcinoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-locally-advanced-and-metastatic-basal-cell-carcinoma
Image credit: Mikael Häggström, MD. Licensed under CCO 1.0