Cemiplimab Shows Strong Activity in Pivotal Basal Cell Carcinoma Trial

Cemiplimab (Libtayo) induced clinically meaningful and durable responses in patients with advanced basal cell carcinoma who had progressed on or were intolerant to prior hedgehog pathway inhibitor therapy, according to topline phase 2 data announced by Regeneron Pharmaceuticals, Inc., and Sanofi, the codevelopers of the PD-1 inhibitor.¹

Among 84 patients with locally advanced disease, the objective response rate (ORR) was 29% (95% CI, 19-40), the durable disease control rate (DCR; response or stable disease ≥6 months) was 60% (95% CI, 48-70), and 85% of responders had an estimated duration of response (DOR) ≥1 year. A preliminary analysis of 28 patients with metastatic disease showed an ORR of 21% (95% CI, 8-41) and a durable DCR of 46% (95%, CI 28-66). In this group, 83% of responders had an estimated DOR ≥1 year.

"We are very encouraged by these clinically-meaningful response rates and durations of response, which are particularly impressive given this is a second-line setting where there are no approved therapies," Israel Lowy, MD, PhD, senior vice president, Translational and Clinical Sciences, Oncology at Regeneron, stated in a press release.

"These data in advanced BCC provide the third instance where Libtayo monotherapy has demonstrated robust and clinically meaningful outcomes in advanced cancer, and follows last week's announcement in advanced non-small cell lung cancer where the pivotal trial was stopped early for positive overall survival," added Lowy.

In the ongoing, single-arm, open-label phase 2 trial, patients receive cemiplimab intravenously at 350 every 3 weeks for a maximum of 93 weeks, or until disease progression, unacceptable toxicity, withdrawal of consent, or confirmed complete response (CR). The primary end point is ORR, with secondary end points including overall survival, progression-free survival, DOR, safety, and quality of life.

No new safety signals with the PD-1 inhibitor have emerged in the trial. The safety population included 132 patients, comprising 84 patients with locally advanced disease and 48 patients with metastatic disease. Overall 95% of patients had at least 1 adverse events (AE), 32% had a serious AE, and AE-related discontinuation occurred in 13% of patients. Among the metastatic patients, there were 9 deaths, and in the locally advanced group, there were 10 deaths; however; none of these deaths were considered to be related to treatment.

The companies plan to share additional data from the study at a future medical meeting.

"While PD-1 inhibitors have transformed the outlook for many patients with melanoma, progress for patients with non-melanoma skin cancers has not been as rapid," Peter C. Adamson, MD, global head of Oncology Development at Sanofi, stated in the press release. "We are continuing to address this unmet need by first bringing Libtayo to patients with advanced cutaneous squamous cell carcinoma, and now, with this second trial, as a potential therapy for patients with advanced basal cell carcinoma. These important new results further demonstrate Libtayo's potential in patients with difficult-to-treat, non-melanoma skin cancers."

Cemiplimab (cemiplimab-rwlc) is currently approved by the FDA for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or patients with locally advanced CSCC who are not candidates for curative surgery or curative radiation.²

The approval was based on a combined analysis of data from the phase 2 EMPOWER-CSCC-1 (Study 1540) trial and 2 advanced CSCC expansion cohorts from a phase I trial (Study 1423). The 108-patient combined analysis included 75 patients with metastatic CSCC and 33 patients with locally advanced CSCC.

Across the entire population, the ORR at a median follow-up of 8.9 months was 47% (95% CI, 38-47). The CR rate was 4% and the partial response (PR) rate was 44%. The duration of response ranged from 1 month to over 15 months. Sixty-one percent of patients had a duration of response ≥6 months.

Among 75 patients with metastatic CSCC, the ORR was 47% (95% CI, 35-59). The CR rate was 5% and the PR rate was 41%. The duration of response ranged from 3 months to over 15 months. Sixty percent of patients had a duration of response ≥6 months. In the 33 patients with locally advanced disease, the ORR was 49% (95% CI, 31-67), comprising all PRs. The duration of response ranged from 1 month to over 13 months. Sixty-three percent of patients had a duration of response ≥6 months.

References

1. Libtayo® (cemiplimab) Shows Clinically-Meaningful and Durable Responses in Second-line Advanced Basal Cell Carcinoma. Published May 5, 2020. https://prn.to/3aZUwhi. Accessed May 5, 2020.
2. FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. Published Sept. 28, 2018. https://bit.ly/2YCgq7R. Accessed May 5, 2020.