FDA Accepts Supplement Biologics License Application for Pembrolizumab in Advanced NSCLC

A supplemental biologics license for adjuvant pembrolizumab (Keytruda) has been accepted by the FDA for patients with stage IB, II, or IIIA non–small cell lung cancer (NSCLC) after a complete resection, according to a press release from Merck.

This review is based on results from the phase 3 KEYNOTE-091 trial (NCT02504372) or the EORTC-1416-LCG/ETOP-8-15-PEARLS, which assessed the immunotherapy agent in completely resected early-stage NSCLC. Findings from the study were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, and the Prescription Drug User Fee Act date was set for January 29, 2023.

“[Pembrolizumab] is foundational in the treatment of metastatic [NSCLC]. The acceptance of our application demonstrates the progress we are making in earlier lines and earlier stages of certain cancers across our oncology portfolio,” Eliav Barr, MD, senior vice president, head of Global Clinical Development and chief medical officer of Merck Research Laboratories, said in the press release. “If approved, [pembrolizumab] would be the first adjuvant immunotherapy-based option in the US for patients with stage IB (≥4 centimeters) to IIIA [NSCLC] following surgical resection regardless of PD-L1 expression.”

In the study, 1117 patients enrolled and were randomized 1:1 to either the pembrolizumab arm (n = 590) or the placebo arm (n = 587). Patients were then further stratified based on PD-L1 expression, with 168 in the pembrolizumab arm and 165 in the placebo arm. Patients were treated with pembrolizumab at 200 mg every 3 weeks up to 18 cycles or matched placebo.

Patient characteristics for the overall cohort included a median age of 65 for both arms. Two-thirds of patients were men and the majority were treated in Western Europe. An ECOG performance score of 1 was reported in 35.6% of patients in the pembrolizumab arm and 41.6% in the placebo arm, 85.3% vs 88.8% were current or former smokers, and 67.5% vs 61.8% had nonsquamous histology. Additionally, 85.8% of patients in the pembrolizumab group previously received adjuvant chemotherapy vs 85.9% in the placebo group. Stage II disease was the most common, including 55.8% vs 57.6% of patients in each group, respectively. EGFR mutations were seen in 6.6% of patients in the pembrolizumab arm vs 5.8% in the placebo arm, with ALK translocation occurring in 1.2% each.

A lobectomy was performed in 78.1% of patients in the pembrolizumab arm vs 79.0% in the placebo arm. Moreover, a tumor status of 0 was reported in 39.5% vs 43.8% and a status of 1 was reported in 39.5% vs 38.0% of patients, respectively. Over half of patients in either arm had a tumor size of 4 cm or greater (57.1% vs 59.3%), respectively.

The median disease-free survival (DFS) was 53.6 months (95% CI, 39.2–not reached [NR]) in the pembrolizumab arm and 42.0 months (95% CI, 31.3-NR) in the placebo arm (HR, 0.76; 95% CI, 0.63-0.91; P = .0014). Additionally, the median DFS for those with PD-L1 tumor proportion score of 50% or more was NR in either the pembrolizumab group (95% CI, 44.3-NR) or the placebo group (95% CI, 35.8-NR; HR, 0.82; 95% CI, 0.57-1.18; P = .014).

When assessing DFS outcomes characterized by baseline factors, investigators reported a trend favoring the pembrolizumab arm. This included factors such as receipt of bilobectomy (HR, 0.85; 95% CI, 0.43-1.69), lobectomy (HR, 0.78; 95% CI, 0.64-0.96), and pneumonectomy (HR, 0.71; 95% CI, 0.40-1.24); lymph node status involvement of pN0 (HR, 0.63; 95% CI, 0.46-0.86) or pN1 (HR, 0.77; 95% CI, 0.57-1.03); and tumor size of 4 cm or less (HR, 0.91; 95% CI, 0.69-1.20) or greater than 4 cm (HR, 0.70; 95% CI, 0.55-0.89).

References

1. FDA accepts application for Merck’s Keytruda (pembrolizumab) as adjuvant therapy for stage IB (≥4 centimeters)-IIIA non–small cell lung cancer following complete surgical resection. News Release. Merck. June 13, 2022. Accessed June 14, 2022. https://bit.ly/3tA7ped
2. O’Brien M, Paz-Ares L, Jha N, et al. EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study of pembrolizumab versus placebo for completely resected early-stage non-small cell lung cancer (NSCLC): outcomes in subgroups related to surgery, disease burden, and adjuvant chemotherapy use. J Clin Oncol. 2022;40(suppl 16):8512-8512. doi: 10.1200/JCO.2022.40.16_suppl.8512