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From 20-30% of patients with advanced basal cell carcinoma (BCC) responded to the PD-1 inhibitor cemiplimab (Libtayo) after resistance or intolerance to a hedgehog-pathway inhibitor, according to updated findings from a phase II trial.

Overall response data included 21.4% of patients with locally advanced BCC and 31% of those with metastatic disease. Duration of response had yet to be reached in the subgroup with locally advanced disease but was predicted to continue for at least 12 months. In the subgroup with metastatic disease, all responses were ongoing after a year of treatment.

"Cemiplimab is the first agent that seems to provide clinically meaningful antitumor activity, including durable responses, in patients with locally advanced basal cell carcinoma, and now in this cohort of patients with metastatic basal cell carcinoma, who previously progressed or were intolerant to hedgehog therapy," Karl Lewis, MD, of the University of Colorado Anschutz Medical Campus in Aurora, reported during a press briefing prior to the . "The safety profile is consistent with previous reports, and the data is currently under priority review at the FDA."

Advanced BCC that does not respond to hedgehog-pathway inhibition "constitutes a really terrible disease," and a phase II trial showing activity with cemiplimab in those patients is a major development, commented press briefing moderator Mario Sznol, MD, of Yale School of Medicine in New Haven, Connecticut. Previous evidence had been limited to case reports.

As compared with cemiplimab's activity in cutaneous squamous cell carcinoma (SCC), the onset of response in BCC appeared delayed, Sznol continued, asking about potential mechanistic differences in the two types of skin cancer.

"In the locally advanced cohort in particular, responses seemed to be delayed, and it's not clear why," said Lewis. "Clearly, they are different tumors [SCC and BCC] and the immunologic infiltrates around the tumors are different. Hopefully, with longer follow-up we might see the response rate [in BCC] improve."

Currently, no FDA-approved options exist for advanced BCC that progresses during or after treatment with a hedgehog inhibitor (HHI) or for patients who cannot tolerate an HHI. As Sznol pointed out, case reports provided evidence of cemiplimab activity in such patients.

Investigators in a pivotal phase II trial examined the safety and efficacy of cemiplimab in patients with locally advanced/metastatic BCC that progressed during or after treatment with an HHI or who were intolerant to the therapy. Initial results for patients with locally advanced BCC at the European Society for Medical Oncology virtual meeting. Lewis reviewed the initial results and reported findings from a prespecified analysis of patients with metastatic BCC.

Data analysis included 84 patients with locally advanced BCC and 28 patients with metastatic disease. Treatment continued until disease progression or development of unacceptable toxicity. The primary endpoint was objective response rate (ORR), as determined by independent central review.

As previously reported, cemiplimab led to an ORR of 31% in patients with locally advanced BCC, including complete responses in five patients (6%). An additional 41 patients (48.8%) had stable disease as best response to treatment. Median duration of response had yet to be reached at data cutoff, but the probability of ongoing response at 6 months was 90.9% and 85.2% at 12 months.

All 28 patients with metastatic disease had already received vismodegib (Erivedge), three had received sonidegib (Odomzo), and three had received both drugs. Three-fourths of the patients had disease progression with prior HHI therapy.

Lewis reported response data for 28 patients followed for approximately 57 weeks. Six patients (21.4%) achieved partial responses with cemiplimab, and 10 (35.7%) had stable disease, resulting in a disease control rate of 57.1%. The median duration of response had yet to be reached, but the probability of ongoing response at 6 months was 100% and 66.7% at 12 months. All of the responses had an observed duration of at least 8 months.

Five patients had grade ≥3 treatment-related adverse events, and one patient died of staphylococcal pneumonia, which was considered unrelated to study treatment.

The future role of cemiplimab in advanced BCC remains undetermined, but the potential for use in the first-line setting -- before an HHI -- is an important issue, Lewis said in response to a question.

"Hedgehog inhibitor therapies are very difficult to tolerate. They have a lot of toxicities," he said. "Whether a PD-1 inhibitor at some point can be used as front-line therapy will be something that needs to be answered."

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