Merck's Keytruda bounces back from pair of trial flops with ⁠interim win in earlier lung cancer

One day after a double-pronged loss in prostate and lung cancer, Merck & Co.’s immuno-oncology superstar Keytruda is bouncing back.

In the phase 3 Keynote-671 study, Keytruda hit one of two primary endpoints—event-free survival—in patients with resectable stage 2, 3A or 3B non-small cell lung cancer (NSCLC). With half a win in hand, Merck says it will continue to watch the trial for the readout of the other overall-survival endpoint.

Event-free survival refers to the time a patient lives without disease complications such as tumor progression or death after trial randomization. 

In tandem with the data drop, Merck said the FDA has accepted its application for Keytruda in earlier-stage NSCLC, teeing up a decision date of Oct. 16. An approval would see Keytruda move into resectable stage 2, 3A or 3B NSCLC in combination with platinum chemotherapy before surgery and as a solo agent post-surgery.  

The trial compared the Keytruda regimen against placebo and chemo before surgery and placebo alone after surgery. Merck plans to divulge more details on the Keynote study at an upcoming medical meeting but described the EFS improvement as statistically significant and clinically meaningful.

Moreover, the drug hit statistically significant improvements on secondary endpoints like pathological complete response and major pathological response.

By moving the Keytruda regimen into earlier stages of disease, the company thinks it “may be able to significantly reduce the risk of recurrence for these patients,” Eliav Barr, M.D., Merck’s SVP and head of global clinical development and chief medical officer of Merck Research Laboratories, said in a statement.

The Keytruda win comes right on the heels of back-to-back losses for the drug. On Tuesday, Merck disclosed a phase 3 trial flop for Keytruda in tandem with Pfizer and Astellas’ Xtandi in metastatic castration-resistant prostate cancer (mCRPC) patients who hadn’t received prior chemotherapy. The PD-1 inhibitor failed to stave off cancer progression as well, prompting Merck to ax the study, known as Keynote-641.

On Keytruda’s home turf in NSCLC, pairing the med with chemotherapy didn’t significantly prolong the lives of patients with nonsquamous EGFR-mutated tumors after progression on AstraZeneca’s Tagrisso, results from the phase 3 Keynote-789 study showed.

The current Keynote-671 win comes against the backdrop of a wider perioperative NSCLC war Keytruda is waging with Roche's Tecentriq and Bristol Myers Squibb's Opdivo. On that front, Keytruda was recently cleared for use after surgery and chemotherapy for early NSCLC across stages 1B, 2 or 3A. The green light bodes ill for Tecentriq, which has a narrower indication in the postsurgery adjuvant NSCLC setting. As for immunotherapy use before surgery in the neoadjuvant setting, Opdivo was the first to snag an FDA go-ahead.