Merck Halts 2 Phase 3 KEYNOTE Studies of Pembrolizumab in Lung and Skin Cancers
The phase 3 KEYNOTE-867 and KEYNOTE-630 studies will be stopped due to futility, following analysis from independent data monitoring committees.
Illustration of a tumor sample under a microscope: © catalin - stock.adobe.com
Merck is halting the phase 3 KEYNOTE-867 study (NCT03924869) and KEYNOTE-630 study (NCT03833167) of pembrolizumab (Keytruda) due to futility, based on recommendations from an independent data monitoring committee.1
KEYNOTE-867 was evaluating pembrolizumab, the anti–PD-1 therapy, in combination with stereotactic body radiotherapy (SBRT) for the treatment of stage I or II non–small cell lung cancer (NSCLC). At a prespecified interim analysis, pembrolizumab plus SBRT did not appear to show an improvement in event-free survival (EFS) or overall survival (OS) compared with placebo and SBRT. Pembrolizumab plus SBRT was also associated with a higher incidence of adverse events (AEs), including AEs leading to death.
In KEYNOTE-630, investigators were evaluating pembrolizumab for the treatment of high-risk, locally advanced cutaneous squamous cell carcinoma (cSCC) following surgery and radiation. The risk/benefit profile did not support continuing the trial, and a prespecified interim analysis showed that pembrolizumab did not lead to a statistically significant improvement in recurrence-free survival (RFS). At the time of this analysis, data for OS did not appear to favor pembrolizumab.
“Our understanding of cancer and how it can be treated has rapidly evolved in recent years, but unmet needs remain across different types of cancer and stages of disease,” said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in a press release. “That is why we continue our rigorous exploration of innovative treatment approaches in cancers with high unmet need, such as non–small cell lung cancer and cutaneous squamous cell carcinoma, with the goal to help even more patients. We are extremely grateful to all of the patients, caregivers and investigators for their participation in these studies.”
About KEYNOTE-867
The phase 3, randomized, double-blind KEYNOTE-837 enrolled an estimated 436 patients who were randomized 1:1 to receive 200 mg of pembrolizumab every 3 weeks for up to 17 cycles plus SBRT or placebo plus SBRT. The primary end point was EFS, and secondary end points included OS and safety.2
Patients were eligible for enrollment if they had an ECOG performance status of 0 to 2 and adequate organ function within 7 days of the start of study treatment and if they were unable to receive surgery or refused surgery. Those who previously received anti–PD-1 or anti–PD-L1 therapy or prior radiotherapy to the thorax, or those with active infections or autoimmune disease were not eligible for study participation.
About KEYNOTE-630
The phase 3, randomized, double-blind KEYNOTE-630 enrolled an estimated 430 patients who were randomized to receive 400 mg of pembrolizumab or placebo as adjuvant therapy following surgery and radiation. The primary end point was RFS, and key secondary end points included OS and safety.3
Patients were eligible for enrollment if they had an ECOG performance status of 0 to 1, at least 1 high-risk disease feature, and a life expectancy of at least 3 months. Those who had any other histologic type of skin cancer other than cSCC, received prior therapy with an anti–PD-L2 or CTLA-4 agent, or not recovered from radiation-related toxicities were not eligible for enrollment.
REFERENCES:
1. Merck provides update on phase 3 KEYNOTE-867 and KEYNOTE-630 trials. News release. Merck. August 29, 2024. Accessed August 30, 2024. https://tinyurl.com/9f2tp94p
2. Efficacy and safety study of stereotactic body radiotherapy (SBRT) with or without pembrolizumab (MK-3475) in adults with unresected stage I or II non-small cell lung cancer (NSCLC) (MK-3475-867/KEYNOTE-867). ClinicalTrials.gov. Updated December 15, 2023. Accessed August 30, 2024. https://clinicaltrials.gov/study/NCT03924869
3. Pembrolizumab (MK-3475) versus placebo following surgery and radiation in participants with locally advanced cutaneous squamous cell carcinoma (MK-3475-630/KEYNOTE-630). ClinicalTrials.gov. Updated April 16, 2024. Accessed August 30, 2024. https://clinicaltrials.gov/study/NCT03833167
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