FDA Approval Sought for Frontline Pembrolizumab Combo in Squamous NSCLC


A supplemental biologics license application has been submitted to the FDA for the use of pembrolizumab in combination with standard chemotherapy as a treatment for patients with metastatic squamous non–small cell lung cancer.

A supplemental biologics license application (sBLA) has been submitted to the FDA for the use of pembrolizumab (Keytruda) in combination with standard chemotherapy as a treatment for patients with metastatic squamous non—small cell lung cancer (sNSCLC), according to Merck (MSD), the manufacturer of the PD-1 inhibitor.

The sBLA is based on findings from the phase III KEYNOTE-407 trial (NCT02775435), which evenly randomized 560 treatment-naive patients with metastatic squamous NSCLC to pembrolizumab combined with carboplatin/paclitaxel or nab-paclitaxel (Abraxane), carboplatin/paclitaxel alone, or nab-paclitaxel alone. The coprimary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and duration of response.

Merck announced today that an interim analysis of early KEYNOTE-407 participants has shown that the secondary endpoint of improved ORR with pembrolizumab has been met. According to the company, data from the study will be presented at the 2018 ASCO Annual meeting, potentially including additional results from another interim analysis expected prior to the conference.

Frontline combination treatment with pembrolizumab and chemotherapy is already approved by the FDA for patients with nonsquamous NSCLC. In May 2017, the FDA granted an accelerated approval to pembrolizumab for use in combination with pemetrexed (Alimta) plus carboplatin as a frontline treatment for patients with metastatic or advanced nonsquamous NSCLC, regardless of PD-L1 expression.

The accelerated approval was based on cohort G in the KEYNOTE-021 trial, in which the 12-month PFS rate was 56% with pembrolizumab combined with pemetrexed and carboplatin compared with 34% with chemotherapy alone (HR, 0.50; 95% CI, 0.29-0.84; P = .0038).1

Last month, the FDA granted a priority review to a supplemental biologics license application (sBLA) to convert this accelerated approval into a full approval. The sBLA is based on the phase III KEYNOTE-189 trial, in which adding pembrolizumab to pemetrexed and either cisplatin or carboplatin in the first-line setting reduced the risk of death by over 50% in patients with NSCLC without EGFR or ALK mutations.2,3

At a median follow-up of 10.5 months, the estimated 12-month overall survival (OS) rate was 69.2% (95% CI, 64.1-73.8) in the pembrolizumab arm compared with 49.4% (95% CI, 42.1-56.2) in the control group (HR, 0.49; 95% CI, 0.38-0.64; P <.001).

The median OS was not reached in the pembrolizumab cohort, compared with 11.3 months (95% CI, 8.7-15.1) in the chemotherapy-alone arm. The OS benefit was observed, irrespective of PD-L1 status. The study also met the coprimary endpoint of progression-free survival (PFS), with a median PFS of 8.8 months (95% CI, 7.6-9.2) in the pembrolizumab group versus 4.9 months (95% CI, 4.7-5.5) in the control arm (HR, 0.52; 95% CI, 0.43 to 0.64; P <.001).

Pembrolizumab is already approved as a single agent for the treatment of patients with metastatic squamous NSCLC.


  1. Papadimitrakopoulou V, Gadgeel SM, Borghaei H, et al. First-line carboplatin and pemetrexed (CP) with or without pembrolizumab (pembro) for advanced nonsquamous NSCLC: Updated results of KEYNOTE-021 cohort G. J Clin Oncol. 2017;35 (suppl; abstr 9094).
  2. Gandhi L, Rodgríguez-Abreu D, Gadgeel S, et al. KEYNOTE-189: Randomized, double-blind, phase 3 study of pembrolizumab (pembro) or placebo plus pemetrexed (pem) and platinum as first-line therapy for metastatic NSCLC. Presented at 2018 AACR Annual Meeting; April 14-18, 2018; Chicago, Illinois. Abstract CT075.
  3. Gandhi L, Rodgríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non—small-cell lung cancer [published online April 16, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1801005.
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