FDA Approves Cemiplimab for Locally Advanced and Metastatic Basal Cell Carcinoma

The FDA has approved cemiplimab-rwlc (Libtayo), the PD-1 inhibitor, for the treatment of patients with advanced basal cell carcinoma (BCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is not appropriate.¹

This indication marks the first immunotherapy approved for advanced BCC after hedgehog pathway inhibition. A full approval was granted for patients with locally advanced BCC and an accelerated approval was granted for patients with metastatic disease.

“Today’s FDA approval of Libtayo will change the treatment paradigm for patients with advanced basal cell carcinoma,” trial investigator Karl Lewis, MD, professor in the Division of Medical Oncology at the University of Colorado, said in a statement. “Advanced basal cell carcinoma is a persistent, painful, and highly disfiguring cancer. While the primary systemic treatment options are hedgehog inhibitors, many patients will eventually progress on or become intolerant to this therapy. With Libtayo, these patients now have a new immunotherapy option that has demonstrated clinically meaningful and durable anti-tumor responses in locally advanced BCC.”

Approval in the locally advanced setting was based on a primary analysis from a pivotal phase 2 trial (NCT03132636), which was presented at the European Society of Medical Oncology Congress 2020,² and approval in the advanced setting was based on an interim analysis of a second cohort of the same study, which was presented at the 35th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer.³

The open-label, multicenter, nonrandomized phase 2 trial enrolled patients with unresectable locally advanced or metastatic (nodal or distant) BCC and was the largest prospective clinical trial in this patient population. All patients had either progressed on a hedgehog pathway inhibitor, were intolerant of hedgehog inhibition, or had not responded to treatment after 9 months. Treatment with cemiplimab was administered at 350 mg every 3 weeks until progressive disease.

The primary end point of the study was confirmed objective response rate (ORR) by independent central review, and secondary end points included duration of response (DOR), overall survival (OS), progression-free survival (PFS), patient-reported outcomes, and safety.

In the locally advanced cohort, among 84 evaluable patients, the median age was 70 year (range, 42-89), 60.7% had an ECOG performance status of 0, and the primary site of disease was the head and neck for 89.3%.

At a median follow-up of 15.1 months, the ORR was 29% (95% CI, 19%-40%) in this cohort, which consisted of complete responses in 6% and partial responses in 23%. The median DOR was not reached (range, 2-21+ months), and 79% had responses lasting at least 6 months.

The metastatic BCC cohort included 28 evaluable patients who were followed for a median of 9.5 months as of the interim analysis. The ORR was 21% (95% CI, 8%-41%), with partial responses in all patients. The median DOR was not reached (range, 9-23+ months) and all patients had responses lasting at least 6 months.

Responses in this cohort were observed regardless of PD-L1 expression levels.

The most common adverse events across the cohorts included fatigue, musculoskeletal pain, diarrhea, rash, pruritus and upper respiratory tract infection. Serious adverse events were reported in 32% of patients, with the most common events being urinary tract infection, colitis, acute kidney injury, adrenal insufficiency, anemia, infected neoplasm and somnolence. Thirteen percent of patients discontinued treatment due to adverse events, most often due to colitis or physical health deterioration.

No treatment-related deaths were reported, and the safety profile was generally consistent with previous reports for cemiplimab.

Cemiplimab is also approved for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. The PD-1 inhibitor is also under priority review for an indication in non–small cell lung cancer, with a decision expected by late February 2021.

_References:

_{1. FDA approves Libtayo® (Cemiplimab-rwlc) as first immunotherapy indicated for patients with advanced basal cell carcinoma. News release. Sanofi. February 9, 2021. Accessed February 9, 2021. https://bit.ly/3tGTQIf}

_{2. Stratigos AJ, Sekulic A, Peris K, et al. 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). Presented at 2020 Virtual ESMO Congress; September 19-October 21, 2020; Virtual. Abstract LBA47.}

_{3. Lewis KD, Peris K, Sekulic A, et al. 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). Poster presented at: Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting & Pre-Conference Programs; November 9-14, 2020; Virtual Abstract 428.}