Merck’s Keytruda Wins Approval for Yet Another Lung Cancer Indication

^{Katherine Welles / Shutterstock}

There’s little doubt that Merck’s checkpoint inhibitor Keytruda (pembrolizumab) is about as close to a miracle drug as we get. The U.S. Food and Drug Administration (FDA) approved the anti-PD-1 checkpoint inhibitor for yet another indication, this time as a monotherapy for the first-line treatment of stage III non-small cell lung cancer (NSCLC) in patients who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and patients whose tumors express PD-L1 as identified on an FDA-approved companion diagnostic, with no EGFR or ALK genomic tumor aberrations.

The approval for this expanded label is based on the Phase III KEYNOTE-042 clinical trial. In that trial, Keytruda alone showed a significant improvement in overall survival compared with chemotherapy in this patient population. There was originally an earlier date, but Merck submitted additional data late in 2018, and on December 20, the company indicated the agency found it made up a major amendment and extended the target action date three months to April 11, 2019.

“This expanded first-line indication now makes Keytruda monotherapy an option for more patients with non-small cell lung cancer, including those for whom combination therapy may not be appropriate,” stated Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories.

Keytruda was the first anti-PD-1 checkpoint inhibitor therapy to be approved in metastatic NSCLC as a first-line choice either alone or in combination.

Merck indicates that Keytruda is currently in more than 900 clinical trials in a broad range of cancers and treatment settings.

KEYNOTE-042 was a randomized, multi-center, open-label, active-controlled Phase III trial in patients with Stage III NSCLC in which it would not be appropriate for surgical resection or definitive chemoradiation. Another group of patients had metastatic NSCLC whose tumors expressed PD-L1 but had not received previous systemic treatment for metastatic NSCLC.

Patients who were ineligible for KEYNOTE-042 had EGFR or ALK genomic tumor aberrations, autoimmune disease requiring systemic therapy within the last two years, were immunosuppressed or had received more than 30 Gy of radiation in the thoracic area within 26 weeks before the trial started.

The trial enrolled 1,274 patients who were randomized 1:1 to either receive Keytruda 200 mg intravenously every three weeks or the investigator’s choice of two different chemotherapy approaches, pemetrex every three weeks plus carboplatin every three weeks on Day 1 for up to six cycles followed by optional pemetrexed every three weeks or paclitaxel every three weeks and carboplatin every three weeks on Day 1 for up to six cycles followed by optional pemetrexed every three weeks.

Merck has had a lot of recent approvals for Keytruda. On March 14, 2019, the company announced that the European Commission had approved Keytruda in combination with carboplatin and either paclitaxel or nab-paclitaxel, for first-line treatment of adults with metastatic squamous non-small cell lung cancer (NSCLC). On April 1, Merck announced that Keytruda had been approved by China’s National Medical Products Administration (NMPA) in combination with pemetrexed and platinum chemotherapy for first-line treatment of metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor mutations.

At the recent American Association for Cancer Research (AACR) meeting, Merck presented results from a post-hoc analysis of patients with liver or brain cancers from the Phase III KEYNOTE-189 trial. The point of the post-hoc analysis was to evaluate outcomes of Keytruda in combination with chemotherapy in liver and brain cancers.

The company also presented pooled data from KEYNOTE-158 and Phase Ib KEYNOTE-028 evaluating Keytruda in patients with previously treated advanced small cell lung cancer (SCLC). Data from these trials supported the company’s first application in SCLC for Keytruda. The sBLA was accepted by the FDA for priority review and has a target action date of June 17, 2019.