TARRYTOWN, N.Y. & PARIS—Regeneron Pharmaceuticals Inc. and Sanofi S.A. recently reported top-line data from a Phase 2 trial for Libtayo in patients with advanced basal cell carcinoma (BCC) who had progressed on, or were intolerant to, prior hedgehog pathway inhibitor (HHI) therapy. Libtayo demonstrated clinically meaningful and durable responses.
“Like other PD-1 inhibitors, Libtayo (cemiplimab) is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation,” says Matthew Fury, executive medical director of Clinical Sciences in Oncology at Regeneron.
“Regeneron and Sanofi were the first to recognize the potential of PD-1 inhibition to treat non-melanoma skin cancers like basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC). These cancers have some of the highest tumor mutational burdens among all cancers, and we hypothesized that they would be particularly responsive to PD-1 inhibition,” Fury continues. “This led us to investigate Libtayo in pivotal trials for both advanced BCC and CSCC. Our trials in advanced CSCC were the first to have results and have supported multiple global approvals for Libtayo in this indication, where it is now the standard of care.”
BCC is the most common cancer worldwide, with approximately two million new cases diagnosed each year in the U.S. alone. While the vast majority of BCCs are caught early and are easily cured with surgery and/or radiation, a small percentage of tumors can become locally advanced and penetrate deeper into the surrounding tissues. This makes the tumors more difficult to treat.
For this ongoing trial, patients received Libtayo 350 mg intravenously every three weeks for up to 93 weeks, or until disease progression, unacceptable toxicity, withdrawal of consent or confirmed complete response. Objective response rate (ORR) is the primary endpoint; key secondary endpoints include overall survival, progression-free survival, duration of response, safety and quality of life.
ORR for patients (n=84) with locally advanced disease was 29 percent, with an estimated duration of response (DOR) exceeding one year in 85 percent of responders. The durable disease control rate (DCR) was 60 percent. In a preliminary analysis of patients (n=28) with metastatic disease, the ORR was 21 percent, with an estimated DOR exceeding one year in 83 percent of responders. The durable DCR was 46 percent. All data were assessed by an independent central review. Data are expected to continue to evolve, with further follow-up across both patient groups.
“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,” stated Dr. Israel Lowy, senior vice president of Translational and Clinical Sciences in Oncology at Regeneron. “These data in advanced BCC provide the third instance where Libtayo monotherapy has demonstrated robust and clinically meaningful outcomes in advanced cancer, and follow last week’s announcement in advanced non-small cell lung cancer where the pivotal trial was stopped early for positive overall survival.”
There were no new safety signals in the trial. Among the 132 patients assessed for safety, 95 percent experienced an adverse event (AE), 32 percent had a serious AE and 13 percent discontinued the trial due to an AE. There were 10 deaths in the locally advanced group and nine deaths in the metastatic group, none of which were considered treatment-related. Regeneron and Sanofi plan to present additional trial findings at an upcoming medical meeting.
Analysts from SVB Leerink LLC point out that the ORR for Libtayo may be low, but they believe that the long DOR should secure a second indication for the therapeutic.
“Overall, we were a little disappointed at the efficacy and safety data presented, but still see the dataset as approval in an indication with very limited treatment options. We expect extended treatment to only be used by a relatively small subset of BCC patients, but expect it to be approved given lack of other treatment options,” the analysts note. “We expect BCC to be a small indication for Libtayo, with potential peak sales of $200-$250mm for the PD-1 class.”
“One recent analysis with a small sample size (n=16) showed 38 percent of metastatic BCC patients responded to chemotherapy. Despite the lower ORR rate showed by Libtayo, we still think an immunotherapy like Libtayo (if approved) is likely preferred before the systemic chemotherapy, given its mechanism of action and likely less side effects associated with treatment,” the analysts added. “The relatively long duration of response of Libtayo can also help postpone the need for chemotherapy.”
Libtayo is jointly developed and commercialized by Regeneron and Sanofi under a global collaboration agreement. BCC is the second non-melanoma skin cancer for which Libtayo has demonstrated first-in-class data, and follows its initial U.S. approval in CSCC in 2018.
“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,” remarked Dr. Peter C. Adamson, global head of Oncology Development at Sanofi. “These important new results further demonstrate Libtayo’s potential in patients with difficult-to-treat, non-melanoma skin cancers.”
“Based on these Phase 2 data in BCC, we are working as quickly as possible to submit regulatory applications to the U.S. Food and Drug Administration later this year, as well as to other health authorities,” concludes Fury. “Beyond non-melanoma skin cancers, Libtayo is also being investigated in Phase 3 trials in non-small cell lung cancer and cervical cancer, as well as in trials combining Libtayo with novel therapeutic approaches for both solid tumors and blood cancers.”
