KEYNOTE-010 trial of Keytruda (pembrolizumab) meets primary objective in NSCLC-Merck Inc

Merck has announced topline results from the KEYNOTE-010 study of Keytruda (pembrolizumab) in advanced non-small-cell lung cancer (NSCLC) demonstrating that the trial met its primary objective. KEYNOTE-010 is a randomised, pivotal Phase II/III trial comparing two doses of pembrolizumab (the FDA-approved 2 mg/kg dose and a higher, investigational 10 mg/kg dose, both given every 3 weeks), to docetaxel, a commonly used chemotherapy. Patients who had failed prior systemic therapy for advanced NSCLC and whose tumours had PD-L1 (programmed death ligand-1) expression tumour proportion scores (TPS) of 1% or more were enrolled. Outcomes were assessed in patients whose tumours were strongly PD-L1 positive (defined as TPS of 50% or more), and in all PD-L1 positive patients.

A topline analysis revealed that treatment with pembrolizumab was associated with longer overall survival (OS) compared with docetaxel treatment. This was true for both the approved and the investigational doses of pembrolizumab, which showed similar efficacy. It was also true in both the first set of patients analysed (those with a TPS of 50% or greater) and for all enrolled patients. Treatment with pembrolizumab at both doses also provided superior progression-free survival (PFS) versus that achieved following treatment with docetaxel in patients whose tumours had TPS values ≥50%. For PFS, pembrolizumab treatment was numerically but not statistically superior to docetaxel in the all PD-L1 positive group, again at both doses. The safety profile of pembrolizumab in this trial was consistent with that observed in previously reported studies in patients with advanced NSCLC.

Comment: Bristol-Myers Squibb, with its anti-PD1 product Opdivo (nivolumab), remains ahead of Merck and other competitor Roche, and fourth runner AstraZeneca, in the NSCLC indication.

Comment: Both dosages of pembrolizumab showed a statistically significant improvement in overall survival, but failed to reach that improvement on the measure of progression-free survival for the whole patient population. Results were seen as "mixed".