NSCLC and CSCC Trials Discontinued Due to No Efficacy Benefit With Pembrolizumab/SBRT

Trials assessing NSCLC and cutaneous squamous cell carcinoma were discontinued due to no benefit observed or improvement noted with the primary end points.

The phase 3 KEYNOTE-867 and KEYNOTE-630 trials assessing pembrolizumab (Keytruda) plus stereotactic body radiotherapy (SBRT) in patients with stage I or II non–small cell lung cancer (NSCLC) and high-risk locally advanced cutaneous squamous cell carcinoma (CSCC), respectively, have been discontinued, according to a press release from Merck, the developer of pembrolizumab.¹

For the KEYNOTE-867 trial, an independent data monitoring committee recommended the discontinuation as there was no improvement in the end point of recurrence-free survival.² The KEYNOTE-630 was recommended for discontinuation because the benefit/risk ratio did not support continuing the trial.³

Continued data analyses are ongoing for both trials and will be shared with the scientific community and regulatory agencies.

“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, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, stated in the press release. “That is why we continue our rigorous exploration of innovative treatment approaches in cancers with high unmet needs, 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 the patients, caregivers, and investigators for their participation in these studies.”

KEYNOTE-867 Trial in NSCLC

Approximately 530 patients were enrolled in the randomized, placebo-controlled study. Patients were randomly assigned 1:1 to receive either thoracic SBRT to the primary tumors for at least 2 weeks plus placebo or 200 mg of pembrolizumab (Keytruda) plus SBRT every 3 days for 3, 4, 5, or 8 fractions. Placebo was given every 3 weeks for 17 cycles plus SBRT once every 3 days for 3, 4, 5, or 8 fractions. This continued until disease recurrence, development, or unacceptable adverse effects.

Stratification occurred during random assignment by either stage I or II, ECOG performance status of 0 to 2, geographic regions of East Asia vs non-East Asia, and reason for not receiving surgery of either medically inoperable or patient refusal.Every 12 weeks an imaging assessment occurred via blinded independent central review (BICR), and continued for 10 or more weeks after SBRT completion, followed by every 16 weeks for 3 years, and then every 6 months.

The primary end points were event-free survival by BICR and overall survival (OS). Secondary end points included time to death or distant metastases, and safety.

Throughout the trial, AEs were monitored until 30 days after the last dose, and 90 days for serious AEs.

KEYNOTE-630 in CSCC

About 430 patients were enrolled in the double-blind, placebo-controlled trial, and assessed adjuvant pembrolizumab at 400 mg intravenously every 6 weeks for up to 9 cycles or matched placebo.

Secondary end points included OS, change from baseline in the EORTC quality of life questionnaire con 30 score, percentage of patients who experience an AE, and percentage of patients who discontinue due to AEs.⁴

Patients were eligible for enrollment if they had histologically confirmed CSCC at the primary site, histologically confirmed locally advanced disease, had undergone complete macroscopic resection of all diseases, and had completed adjuvant radiotherapy. Additionally, patients were enrolled if they had received an adequate postoperative dose or radiation therapy, were disease-free as assessed by the investigators with complete radiographic staging 28 days or more from randomization, and had a life expectancy of at least 3 months.

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://shorturl.at/4sDK6
2. Jabbour SK, Houghton B, Robinson AG, et al. Phase 3, randomized, placebo-controlled study of stereotactic body radiotherapy (SBRT) with or without pembrolizumab in patients with unresected stage I or II non–small cell lung cancer (NSCLC): KEYNOTE-867. J Clin Oncol. 2022;40(16):TPS8507. doi.10.1200/JCO.2022.40.16_suppl.TPS8597
3. Schenker M, Klochikhin M, Kirtbaya D, et al. The KEYNOTE-630 Trial: a phase 3 study of adjuvant pembrolizumab in high-risk locally advanced (LA) cutaneous squamous cell carcinoma (cSCC). Int J Radiat Oncol Biol Phys. 2024;118(5):E81-E82.
4. 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. Accessed August 29, 2024. https://shorturl.at/Ia3vx