Cemiplimab Expands Treatment Portfolio for Patients with Basal Cell Carcinoma

Patients with advanced basal cell carcinoma (BCC), both metastatic and locally advanced, have a new treatment option with the approval of cemiplimab-rwlc (Libtayo). On February 9, the FDA granted regular approval to cemiplimab for patients with locally advanced BCC previously treated with a hedgehog inhibitor (HHI) or for whom a HHI is not appropriate. An accelerated approval was granted for the indication that includes patients with metastatic disease previously treated with a HHI or for whom a HHI is not appropriate.¹

The approvals were based on results from the phase 2 EMPOWER-BCC 1 trial (NCT03132636), which showed the agent elicited an overall response rate (ORR) of 21% (95% CI, 8%-41%) in patients with metastatic BCC (n = 28) and an ORR of 29% (95% CI, 19%-40%) in patients with locally advanced BCC (n = 84). The median duration of response was not reached in either group.2 Among the responders in the locally advanced group, 79% maintained a response at 6 months; all responders in the metastatic group maintained a response at 6 months.

In terms of safety, the agent was well tolerated, and the most common adverse events of any grade in the 132-patient safety population were fatigue (49%), musculoskeletal pain (33%), and diarrhea (29%). Common grade 3/4 adverse events included fatigue (3.8%), decreased appetite, and musculoskeletal pain (1.5% each).²

Alexander J. Stratigos, MD, PhD, a professor of dermatology and venereology in the Department of Dermatology at the University of Athens Medical School in Greece, discussed the effect cemiplimab will have on the treatment landscape of patients with advanced BCC in an interview with OncologyLive®.

Please elaborate on the data reported from the phase 2 study.

This was an open-label, multicenter, nonrandomized phase 2 trial that included patients with unresectable locally advanced BCC, as well as patients with metastatic BCC, either with nodal metastasis or distant metastatic disease. These patients were treated previously treated with HHI therapy. This study was the largest prospective clinical trial among this patient population and included 112 patients in the efficacy analysis, with 84 patients with locally advanced BCC and 28 patients with metastatic BCC.

In advanced BCC, tumors were shown to be responsive to cemiplimab in both patients with metastatic and locally advanced disease. The confirmed ORR was 21% in patients with metastatic disease and 29% in patients with locally advanced disease. The most common adverse reactions reported in the trial in at least 15% of patients were fatigue in 49% of patients, musculoskeletal pain, diarrhea, rash, pruritus, and upper respiratory tract infection. [These are] the usual safety issues we see with other anti–PD-1 therapies.

What is significant about the approval of cemiplimab for patients with advanced BCC?

There have previously been limited treatment options for patients with advanced BCC following either intolerance or progression with HHI therapy. With the FDA approval of cemiplimab, these patients now have a new immunotherapy option for the treatment of advanced BCC after HHI therapy. It’s very encouraging that the trial [results] showed meaningful clinical responses and also durable responses with cemiplimab.

This is the first immunotherapy treatment for patients with advanced BCC. It’s also the first treatment to show a clinical benefit in patients with advanced BCC, either locally advanced or metastatic disease following a HHI therapy in a pivotal trial.

Cemiplimab is a fully humanized monoclonal antibody that targets the immune checkpoint receptor PD-1, which is located on T cells. Like other anti–PD-1 therapies, cemiplimab binds to PD-1 and has been shown to block cancers from suppressing T-cell activation.

Based on the data seen in pretreated patients so far, is there rationale to suggest that cemiplimab may potentially move into the frontline setting at some point, whether alone or in combination with another agent?

The data have been certainly very encouraging in the second-line setting, and the option of using this immunotherapy in this first-line setting is also quite encouraging. This is something that we should consider either as a monotherapy or, as you suggested, [in] combination with other therapies.

Is there any other element of the approval or ongoing or planned research with cemiplimab that investigators should be aware of?

The FDA granted an accelerated approval for the metastatic disease indication for cemiplimab. [Based on this], cemiplimab is continuing to be investigated in this patient group as part of the ongoing phase 2 EMPOWER-BCC 1 study.

[Additionally,] there is research focused on biomarkers as predictors of response to immunotherapy in this particular patient setting. In my opinion, [this approval is] significant news for patients with advanced BCC, and it expands the scope of immunotherapy in this patient setting. We’re very much encouraged by the fact that there is now a treatment showing clinical benefit in patients with advanced BCC following HHI therapy.

References

1. FDA approves cemiplimab-rwlc for locally advanced and metastatic basal cell carcinoma. FDA. Updated February 9, 2021. Accessed September 21, 2021. bit.ly/3FgThup
2. Libtayo. Prescribing information. Regeneron Pharmaceuticals Inc; 2021. Accessed September 21, 2021. bit.ly/3hIBQZG