Topline data for a pivotal, single-arm, open-label trial for Sanofi and Regeneron’s PD-1 inhibitor Libtayo (cemiplimab) in patients with advanced basal cell carcinoma (BCC) who had progressed on or were intolerant to prior hedgehog pathway inhibitor (HHI) therapy was announced.
Libtayo demonstrated clinically meaningful and durable responses in this group of patients for whom there are no approved treatments. Sanofi and Regeneron plan regulatory submissions in 2020.
BCC is a skin cancer and is the most common cancer worldwide, with approximately two million new cases diagnosed every year in the US alone. While the vast majority of BCCs are caught early and cured with surgery or radiation, a small proportion of tumors can become advanced and penetrate deeper into surrounding tissues (locally advanced), which is more difficult to treat.
Approximately 20,000 US patients have advanced BCC and it is estimated that about 3,000 die each year. BCC marks the second non-melanoma skin cancer for which Libtayo has demonstrated first-in-class data and follows its initial US approval in advanced cutaneous squamous cell carcinoma (CSCC) in 2018.
In the trial, the objective response rate (ORR) for patients (n=84) with locally advanced disease was 29% (95% CI: 19%-40%), with an estimated duration of response (DOR) exceeding one year in 85% of responders. The durable disease control rate (DCR —response or stable disease lasting at least 6 months) was 60% (95% CI: 48%-70%). In a preliminary analysis of patients (n=28) with metastatic disease, the ORR was 21% (95% CI: 8%-41%), with an estimated DOR exceeding one year in 83% of responders. The durable DCR was 46% (95% CI: 28%-66%). All data were assessed by an independent central review. Data are expected to continue to evolve with further follow-up across both patient groups.
“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,” said Peter C. Adamson, M.D, global head of Oncology Development at Sanofi. “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.”
There were no new safety signals in this trial. Among the 132 patients assessed for safety (84 locally advanced and 48 metastatic), 95% of patients experienced an adverse event (AE), 32% had a serious AE and 13% discontinued due to an AE. There were 10 deaths in the locally advanced group and nine deaths in the metastatic group; none of the deaths were considered treatment-related. Sanofi and Regeneron will present additional trial findings at an upcoming medical meeting.
“Libtayo is being investigated as a monotherapy treatment and as a foundation therapy for combinations with novel therapeutic approaches being developed by Regeneron and our collaborators,” Israel Lowy, M.D., Ph.D, senior vice president, translational and clinical sciences, 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 follows last week’s announcement in advanced non-small cell lung cancer where the pivotal trial was stopped early for positive overall survival.”
In this ongoing global phase 2 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. ORR is the primary endpoint and key secondary endpoints include overall survival, progression-free survival, duration of response, safety and quality of life.
Libtayo is being jointly developed and commercialized by Sanofi and Regeneron under a global collaboration agreement.
The use of Libtayo to treat advanced BCC is investigational and the safety and efficacy have not been evaluated by any regulatory authority.
Libtayo 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.
Libtayo is the first and only immunotherapy approved in the US, EU, and other countries for adults with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation.
In the US, the generic name for Libtayo in its approved indication is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the US Food and Drug Administration.
The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. In skin cancer, this includes trials in adjuvant and neoadjuvant CSCC. Libtayo is also being investigated in potentially registrational phase 3 trials in non-small lung cancer and cervical cancer, as well as in trials combining Libtayo with novel therapeutic approaches for both solid tumors and blood cancers.