Merck is discontinuing the study after an independent Data Monitoring Committee recommendation, which determined the benefit/risk profile of pembrolizumab in combination with ipilimumab did not support continuing the trial.
Merck announced it will be stopping the phase 3 KEYNOTE-598 trial, which is investigating pembrolizumab (Keytruda) in combination with ipilimumab (Yervoy) compared with pembrolizumab monotherapy for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (tumor proportion score [TPS] ≥50%) with no EGFR or ALK genomic tumor aberrations.
The company is discontinuing the study after an independent Data Monitoring Committee (DMC) recommendation, which determined the benefit/risk profile of the combination did not support continuing the trial.
In total, the study enrolled 568 patients who were randomized 1:1 to receive either:
The co-primary end points for the study are overall survival (OS) and progression-free survival (PFS). Moreover, key secondary end points included objective response rate, duration of response, and safety.
At an interim analysis, the combination of pembrolizumab and ipilimumab demonstrated no incremental benefit in OS or PFS compared with pembrolizumab alone and crossed futility boundaries. Additionally, no new safety signals for pembrolizumab monotherapy were observed, however the combination of pembrolizumab and ipilimumab led to a higher incidence of grade 3 to 5 adverse events (AEs), serious AEs, and AEs leading to discontinuation or death, compared with pembrolizumab monotherapy.
“We conducted KEYNOTE-598 in order to explicitly explore whether combining our anti-PD-1 therapy, [pembrolizumab], with ipilimumab provided additional benefits beyond treatment with [pembrolizumab] alone in the metastatic non-small cell lung cancer setting,” Roy Baynes, MD, PhD, senior vice president and head of global clinical development, as well as chief medical officer at Merck Research Laboratories, said in a press release. “It is very clear that in this study, the addition of ipilimumab did not add clinical benefit but did add toxicity. [Pembrolizumab] monotherapy remains a standard of care for the treatment of certain patients with metastatic non-small cell lung cancer whose tumors express PD-L1.”
Merck indicated it will inform study investigators of the recommendation from the DMC. Of note, the DMC is currently advising that patients in the study also discontinue treatment with ipilimumab/placebo.
Data from this study will be submitted for presentation at an upcoming scientific congress and also communicated to regulatory agencies.
Merck Announces KEYNOTE-598 Trial Evaluating KEYTRUDA® (pembrolizumab) in Combination With Ipilimumab Versus KEYTRUDA Monotherapy in Certain Patients With Metastatic Non-Small Cell Lung Cancer To Stop for Futility and Patients to Discontinue… [news release]. Kenilworth, NJ. Published November 9, 2020. Accessed November 10, 2020. https://www.merck.com/news/merck-announces-keynote-598-trial-evaluating-keytruda-pembrolizumab-in-combination-with-ipilimumab-versus-keytruda-monotherapy-in-certain-patients-with-metastatic-non-small-cell-lung-cancer-to/