A Merck & Co. effort to move its PD-1 behemoth Keytruda into early treatment of lung cancer has reached a dead end, along with another bid to expand into a type of early-stage skin cancer.
Merck has decided to stop the phase 3 KEYNOTE-867 trial for Keytruda in inoperable stage 1 or 2 non-small cell lung cancer, the company said Thursday.
During a planned interim analysis, Keytruda’s addition to radiation not only failed to improve patients’ risk of disease worsening or death, but it led to higher rates of adverse events, including ones that resulted in death, Merck said. The study tested the pairing against stereotactic body radiotherapy alone.
After reviewing the data, an independent data monitoring committee ruled that the benefit-risk profile of the Keytruda-radiotherapy regimen didn’t support continuing the trial, according to Merck.
The flop in early-stage disease doesn’t affect Keytruda's position in metastatic NSCLC, where it’s the first-line standard of care. In October, the PD-1 inhibitor also snagged a key FDA approval as a continuous treatment both before and after surgery in resectable NSCLC.
Still, the early-stage NSCLC setback comes as Merck’s efforts to further enhance Keytruda in metastatic NSCLC have encountered some difficulties, and ahead of a potential challenge from a PD-1/VEGF bispecific antibody by Akeso and Summit Therapeutics.
In two recent back-to-back failures, Merck found that using its AstraZeneca-partnered Lynparza during the maintenance treatment phase of newly diagnosed metastatic NSCLC didn’t work out across nonsquamous and squamous histologies, separately, in two phase 3 studies.
In addition, a combination of Keytruda and Merck’s investigational anti-TIGIT antibody vibostolimab was found to be less effective than the chemotherapy docetaxel in a phase 2 trial in previously treated metastatic NSCLC. Merck still has three ongoing phase 3 trials for MK-7684A, a fixed-dose combo of Keytruda and vibostolimab, in different NSCLC settings.
In the wake of Merck’s latest setback, the search for a viable PD-1/L1 inhibitor in stage 1 or 2 unresected NSCLC is still ongoing for at least one other company. AstraZeneca is conducting the phase 3 PACIFIC-4 trial, testing the addition of its PD-L1 inhibitor Imfinzi to radiotherapy in a similar design to Merck’s KEYNOTE-867 trial. The AZ study started about three months earlier than its Merck counterpart, and it has a separate cohort examining the British pharma’s Tagrisso following radiotherapy in EGFR-mutant tumors.
In a second setback for Keytruda that Merck unveiled Thursday, the New Jersey pharma is discontinuing the phase 3 KEYNOTE-630 trial for Keytruda as an adjuvant treatment in patients with high-risk locally advanced cutaneous squamous cell carcinoma (cSCC) following surgery and radiation.
An independent data monitoring committee recommended that the study be stopped for futility. On the study’s primary endpoint of recurrence-free survival, Keytruda missed the mark in preventing disease recurrence or death compared with placebo. What’s more, patients’ life expectancy also didn’t favor Keytruda, although the overall survival endpoint was not formally tested because of the primary endpoint flop.
Before the latest trial miss, Keytruda gained approvals in recurrent or metastatic cSCC or locally advanced cSCC that’s not curable by surgery or radiation.