Positive neoadjuvant Libtayo monotherapy data in resectable cutaneous squamous cell carcinoma presented at ESMO and published in NEJM

The data, from the primary analysis of a confirmatory Phase II trial, were presented in an oral session at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris and concurrently published in the New England Journal of Medicine (NEJM).

"Regeneron conducted the first pivotal trial of Libtayo in advanced cutaneous squamous cell carcinoma that was unlikely to be curable by surgery or radiation, and we are now studying the utility of Libtayo in earlier stages of this disease. In addition to our neoadjuvant trial, a global Phase III trial of Libtayo is ongoing in the adjuvant setting after surgery and radiation for patients at heightened risk for recurrence," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "In the neoadjuvant trial in stage II to IV cutaneous squamous cell carcinoma presented at ESMO and published in NEJM, Libtayo demonstrated greater than 60% response rates per both pathologic and imaging measures. Libtayo may therefore have expanded utility in earlier stages of cutaneous squamous cell carcinoma as a monotherapy to potentially help avoid surgery, and as part of a combination approach with surgery to facilitate function-preserving resections and minimize disfigurement."

In the confirmatory, multicenter, single-arm Phase II trial, 79 patients received up to four fixed doses of Libtayo every 3 weeks prior to surgery, with 62 receiving all 4 doses and 70 undergoing surgery. Patients experienced the following efficacy : i. 63.3% combined pathologic response rate (50 of 79 patients), with 50.6% (40 patients) achieving the primary endpoint of complete pathologic response (0% viable tumor, excluding a null hypothesis of 25%) and 12.7% (10 patients) experiencing a major pathologic response (>0% and ?10% viable tumor cells) by independent pathologic review. ii. 68% objective response rate (ORR) (54 of 79 patients; 5 complete responses [CR] and 49 partial responses [PR]) per local imaging review. Adverse events (AE) of any grade occurred in 87% of patients, with 17% considered serious. The most common AE was fatigue (n=24). AEs that were ?grade 3 occurred in 18% of patients. The treatment discontinuation rate due to AEs was 1%, and there was one death due to worsening congestive heart failure considered related to treatment. There were no new Libtayo safety signals.

Patient follow-up in the trial is ongoing to assess disease-free survival. A separate global Phase III trial investigating Libtayo in the adjuvant CSCC setting for patients at heightened risk (i.e., due to involvement of multiple lymph nodes, extension of cancer through the lymph node capsule, perineural invasion) for recurrence is enrolling patients.The potential use of Libtayo described above is investigational, and its safety and efficacy has not been evaluated by any regulatory authority for this indication.

See-"Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma"- Neil D. Gross, M.D., David M. Miller, M.D., Ph.D., Nikhil I. Khushalani, M.D., Vasu Divi, M.D., Emily S. Ruiz, M.D., M.P.H., Evan J. Lipson, M.D., Friedegund Meier, M.D., Yungpo B. Su, M.D., Paul L. Swiecicki, M.D., Jennifer Atlas, M.D., Jessica L. Geiger, M.D., Axel Hauschild, M.D., et al. September 12, 2022. DOI: 10.1056/NEJMoa2209813.