Regeneron Pharmaceuticals, Inc. today announced the first presentation of key secondary endpoints for an investigational regimen of PD-1 inhibitor cemiplimab as a neoadjuvant monotherapy in stage II to IV resectable cutaneous squamous cell carcinoma (CSCC).

The results from an international Phase 2 trial were presented in an oral session at the European Society for Medical Oncology (ESMO) Congress 2023 and concurrently published in The Lancet Oncology.

“Advanced, resectable cutaneous squamous cell carcinoma can lead to reduced patient function and quality of life following the cumulative effects of treatment, typically surgery and radiation. Additionally, risk of recurrence and death is a consideration for these patients,” said Neil D. Gross, M.D., F.A.C.S., Director of Clinical Research, Department of Head and Neck Surgery at the University of Texas MD Anderson Cancer Center and principal investigator of the trial.

“Results from both the single-institution pilot trial and the multi-center Phase 2 trial found neoadjuvant cemiplimab was highly active in patients with resectable cutaneous squamous cell carcinoma. These robust responses were durable, translating into event-free survival for the vast majority of patients at one and two years.”

The multicenter, single-arm Phase 2 trial included two parts.

In Part 1, patients (n=79) received cemiplimab 350 mg every three weeks for up to four doses, followed by curative-intent surgery.

Per the primary analysis presented at ESMO 2022 and published in the New England Journal of Medicine, there was a 63.3% (n=50) combined pathologic response rate.

This included a 50.6% (n=40) pathologic complete response rate (pCR; 0% residual viable tumour) and a 12.7% (n=10) major pathologic response rate (MPR; >0% and ≤10% residual tumour cells).

In Part 2, the post-surgical part of the trial, patients who completed curative intent surgery (n=70), received an investigator’s choice of cemiplimab, radiation or observation.

The presentation at this year’s ESMO shared secondary survival endpoints among all 79 patients in the trial, continuing to demonstrate encouraging outcomes at one-year (median duration of follow-up: 19 months; range: 1-30 months), including:

89% event-free survival rate (95% confidence interval [CI]: 79%-94%) at one year, per Kaplan-Meier estimates, with the median not reached

No disease recurrence among patients who achieved a pCR (n=40).

Among those achieving an MPR, 9 of 10 remained disease-free at one year

92% overall survival rate (95% CI: 83%-96%) at one year, per Kaplan-Meier estimates, with the median not reached

Among all patients, adverse events (AE) of any grade occurred in 89% of patients, with 19% being ≥grade 3, and one death due to worsening congestive heart failure considered possibly related to treatment.

Among those who received adjuvant cemiplimab in Part 2 of the trial (n=16), there were two grade 3 serious AEs including worsening cardiomyopathy and hypophysitis (n=1 each) and no deaths considered related to treatment.

“The primary analysis of this Phase 2 trial demonstrated greater than 60% response rates, and it is encouraging that cemiplimab may have utility in this earlier stage of cutaneous squamous cell carcinoma,” said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron.

“These new data add to the growing body of evidence for cemiplimab in this investigational setting where high unmet patient need remains.”

A separate ongoing global Phase 3 trial is investigating cemiplimab 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 after surgery and radiotherapy.

The potential use of cemiplimab described above is investigational, and its safety and efficacy has not been evaluated by any regulatory authority for this indication.

Source: Regeneron Pharmaceuticals, Inc.