Regeneron Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved the PD-1 inhibitor Libtayo (cemiplimab-rwlc) in combination with platinum-based chemotherapy for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 aberrations. Patients must either have metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation. Patients may be treated with this combination irrespective of PD-L1 expression or histology.
“This second FDA approval for cemiplimab-rwlc in advanced non-small cell lung cancer greatly broadens the scope in which a cemiplimab-rwlc-based regimen can be prescribed to encompass a wide range of patients, either as single agent in those with PD-L1 ≥50% or now in combination with chemotherapy irrespective of PD-L1 expression or tumor histology,” said David R. Gandara, M.D., Professor Emeritus and Senior Advisor of the Thoracic Oncology Program at the University of California Davis Comprehensive Cancer Center. “The approval is based on a Phase 3 trial designed to closely resemble a patient population with varied disease presentations that physicians manage in everyday clinical practice. Even with these diverse disease presentations, cemiplimab-rwlc combined with chemotherapy demonstrated a marked increase in overall survival, at a median of 22 months versus 13 months with chemotherapy alone. Clearly, this is an advance which is clinically meaningful for our patients with advanced stage non-small cell lung cancer.”
The FDA approval is based on data from the global Phase 3 trial, EMPOWER-Lung 3, that investigated Libtayo in combination with a physician’s choice of platinum-doublet chemotherapy (Libtayo combination), compared to platinum-doublet chemotherapy alone. The trial enrolled 466 patients with locally advanced or metastatic NSCLC, irrespective of PD-L1 expression or tumor histology, and with no ALK, EGFR or ROS1 aberrations. Among those enrolled, 43% had tumors with squamous histology, 67% had tumors with <50% PD-L1 expression, 15% had inoperable locally advanced disease not eligible for definitive chemoradiation, and 7% had pretreated and clinically stable brain metastases.
“Libtayo is now approved for extending the survival of patients with advanced non-small cell lung cancer as both a monotherapy in high PD-L1 expressors and in combination with chemotherapy irrespective of PD-L1 expression levels, achieving a high bar that has only been met by one other PD-1 targeting agent,” said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. “With this FDA approval, Libtayo can expand its role as a key treatment option for advanced non-small lung cancer, in addition to serving as a standard-of-care for two advanced non-melanoma skin cancers. We are committed to investigating Libtayo through ongoing trials as a monotherapy and as a backbone of combination treatments in multiple cancers. We thank the many investigators, patients and their families who have participated in our pivotal trials.”
Efficacy in EMPOWER-Lung 3 was assessed in 466 patients who were randomized 2:1 to receive either Libtayo 350 mg (n=312) or placebo (n=154) intravenously every 3 weeks, plus histology-specific platinum-doublet chemotherapy. The trial was stopped early based on a recommendation by the Independent Data Monitoring Committee after the Libtayo combination demonstrated a significant improvement in overall survival (OS), the primary endpoint. Efficacy results comparing the Libtayo combination to chemotherapy alone showed a:
- 22-month median OS versus 13 months, representing a 29% relative reduction in the risk of death (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.53 to 0.93; p=0.014). The 12-month probability of survival was 66% for the Libtayo combination versus 56% for chemotherapy, per Kaplan-Meier estimates.
- 8-month median PFS versus 5 months, representing a 44% reduction in the risk of disease progression (HR: 0.56; 95% CI: 0.44 to 0.70; p<0.0001). The 12-month probability of PFS for the Libtayo combination was 38% versus 16% for chemotherapy.
- 43% overall response rate versus 23%.
- 16-month median DOR (range: 2 to 19+) versus 7 months (range: 2 to 19+).
Safety was assessed in 312 patients in the Libtayo combination group (median duration of exposure: 38 weeks) and 153 patients in the chemotherapy group (median duration of exposure: 21 weeks). The most common adverse reactions occurring in >15% of patients were alopecia (37% Libtayo combination, 43% placebo), musculoskeletal pain (30% Libtayo combination, 36% placebo), nausea (25% Libtayo combination, 16% placebo), fatigue (23% Libtayo combination, 18% placebo), peripheral neuropathy (23% Libtayo combination, 19% placebo) and decreased appetite (17% Libtayo combination, 12% placebo). Serious adverse reactions occurred in 25% of patients, with treatment discontinuations due to adverse reactions in 5% and fatal adverse reactions in 6%. No new Libtayo safety signals were observed.
“The approval of Libtayo in the combination setting builds on the monotherapy indication in advanced non-small cell lung cancer and furthers our excitement for what’s to come as we continue our potentially transformative oncology research,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. “Libtayo is the backbone of our oncology strategy, designed to synergistically combine multiple modalities to provide more options for more patients. We look forward to delivering on the promise of our research in other meaningful combinations that leverage Libtayo and our homegrown pipeline of investigational bispecific antibodies.”
“We welcome this latest approval for Libtayo as a first-line combination treatment for appropriate patients with advanced lung cancer,” said Andrea Ferris, President and CEO at the LUNGevity Foundation. “Lung cancer remains one of the most common cancers worldwide, and every new treatment option is an important step forward against this deadly cancer.”