Two Phase 3 Trials of Pembrolizumab in NSCLC, CSCC to Be Discontinued By Merck

Two Phase 3 Trials of Pembrolizumab in NSCLC, CSCC to Be Discontinued By Merck

Merck has discontinued two phase 3 trials—KEYNOTE-867 (NCT03924869) and KEYNOTE-630 (NCT03833167)—assessing pembrolizumab (Keytruda) in non-small cell lung cancer (NSCLC) and cutaneous squamous cell carcinoma (CSCC), respectively, according to a press release.¹

KEYNOTE-867 evaluated pembrolizumab plus stereotactic body radiotherapy (SBRT) in patients with stage I/II NSCLC, including those who could not undergo or refused surgery. KEYNOTE-630 investigated pembrolizumab in patients with high-risk, locally advanced, CSCC following surgery and radiation in the adjuvant setting.¹

Data from KEYNOTE-867 did not demonstrate an improvement in event-free survival (EFS) or overall survival (OS), the primary and key secondary end points, respectively, vs placebo plus SBRT at prespecified interim analysis, leading an independent data monitoring committee to recommend the discontinuation of the trial. Moreover, the risk/benefit profile of the combination did not warrant continuing the study; pembrolizumab plus SBRT was associated with higher rates of adverse effects (AEs) vs SBRT plus placebo, including AEs leading to death.

The data monitoring committee also recommended that KEYNOTE-630 be halted for futility, as the risk/benefit profile did not support the continuation of the trial. Findings from a preplanned analysis demonstrated that treatment with pembrolizumab did not cross the boundary for statistical significance for the trial’s primary end point, recurrence-free survival (RFS). OS, the key secondary end point, was not formally tested but the data did not favor the anti-PD-1 agent vs placebo. The safety profile of pembrolizumab was consistent with previous findings.

“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, stated in the press release.¹ “That is why we continue our rigorous exploration of innovative treatment approaches in cancers with high unmet need, such as NSCLC 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.”

KEYNOTE-867 was a double-blind study that enrolled patients with unresected stage I or II NSCLC who were medically inoperable, including those who could not undergo thoracic surgery due to illness or an anatomically unresectable tumor, or who decided to receive SBRT rather than surgery. Patients also needed to have an ECOG performance status of 2 or less.^1,2

An estimated 436 patients were randomly assigned 1:1 to receive either pembrolizumab at a dose of 200 mg every 3 weeks for up to 17 cycles or placebo on the same dosing schedule. Both arms also were treated with SBRT once every 3 days for 3, 4, 5, or 8 fractions over approximately 2 weeks, for a total of 45 Gy to 70 Gy, pending tumor type and location.

KEYNOTE-630 was a double-blind study that enrolled patients with high-risk, locally advanced CSCC who have undergone surgery with or without positive margins and completed adjuvant radiotherapy. Eligible patients needed to have a life expectancy of more than 3 months and an ECOG performance status of 1 or less. Approximately 430 patients were randomly assigned to receive either intravenous pembrolizumab at a dose of 400 mg every 6 weeks for up to 9 cycles as adjuvant therapy following surgery and radiation or placebo at the same dosing schedule.^1,3

KEYNOTE-867 and KEYNOTE-630 investigators were informed of the discontinuations by Merck. The company also advised patients enrolled on the trials to consult their treatment team to determine their available options. Data analyses for KEYNOTE-867 and KEYNOTE-630 remain ongoing; the findings will be shared with the scientific community and regulatory agencies.

References

1. Merck provides update on phase 3 KEYNOTE-867 and KEYNOTE-630 trials. News release. Merck. August 29, 2024. Accessed August 29, 2024. https://www.merck.com/news/merck-provides-update-on-phase-3-keynote-867-and-keynote-630-trials/
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 29, 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 29, 2024. https://clinicaltrials.gov/study/NCT03833167