The phase 3 LEAP-006 study of pembrolizumab plus lenvatinib and chemotherapy has missed its dual primary end points.
Treatment with pembrolizumab (Keytruda) in combination with lenvatinib (Lenvima) did not achieve a significant improvement in either overall survival (OS) or progression-free survival (PFS) as first-line treatment of adult patients with metastatic, nonsquamous non–small cell lung cancer (NSCLC) who harbored no EGRF, ALK, or ROS1 alteration. With these results, the coprimary end points of the phase 3 LEAP-006 clinical trial (NCT03829319) were not met.1
Data from the LEAP-006, as well as the LEAP-008 trial (NCT03976375), will continue to be evaluated and later reported to the scientific community, according to Merck.
“As a leader in lung cancer research, we continue to try to advance science for our patients by building upon the standard we set several years ago with Keytruda,” said Gregory Lubiniecki, MD, vice president, global clinical development, Merck Research Laboratories, in a press release. “While these results are not what we hoped for, we are proud of the foundational role that [pembrolizumab] has established in the treatment of certain types of lung cancer, and we are committed to continuing to research how we can further improve responses to our medicines for patients with difficult-to-treat forms of the disease.”
In the prior safety-run in analysis of LEAP-006, treatment with pembrolizumab and lenvatinib was considered to have preliminary antitumor activity along with an acceptable safety profile. The analysis included 13 patients who were followed for a median of 7.5 months (range, 5.7-10.3 months). Patients were given a median of 10 (range, 2-12) cycles of treatment.2
The objective response rate (ORR) observed was 69.1% (95% CI, 38.6%-90.0%). All responses were partial responses, and 23.1% of patients had stable disease. Notably, 11 of the 13 patients were alive and 10 progression-free at the data cutoff.
Only 1 dose-limiting toxicity occurred during the safety run-in. Both events were grade 3 hyponatremia shown in patients given cisplatin. Grade 3-5 adverse events (AEs) were observed in 77% of patients, and AEs were treatment-related in 54%.
Eight patients died because of an AE, and 46% of patients experienced immune-mediated AEs. Grade 3 hypertension occurred in 31% of patients, but no patients experienced grade ≥ 3 proteinuria or infusion-related reactions.
LEAP-006 is a phase 3, randomized, placebo-controlled study. In the experimental arm, patients received pemetrexed in combination with platinum-based chemotherapy, and pembrolizumab/lenvatinib for up to 35 cycles. In the comparator arm, patients are treated with pemetrexed plus platinum-based chemotherapy, pembrolizumab, and placebo for up to 35 cycles.2,3
During part 1, the study set out to investigate the coprimary end points of the number of patients with DLTs, the number of patients with 1 or more AE, and the number of patients who discontinue treatment due to an AE. The coprimary end points explored in part 2 of the study were PFS and OS.
Secondary end points explored in LEAP-006 included ORR by blinded independent review committee, duration of response, the number of patients with 1 or more AE, the number of patients who discontinue treatment due to an AE, change from baseline in global health status/quality of life, time to true deterioration, and time to true deterioration in the composite end point.
Patients enrolled in the study were 18 years of age or older with a histologically or cytologically confirmed of stage IV nonsquamous NSCLC. All patients were tested for the absence of EGFR, ALK, or ROS1 alterations. Further, patients were required to have measurable disease per RECIST v1.1, a life expectancy of 3 months, and an ECOG performance status of at 0 or 1. Patients were also required to have adequate organ function and controlled blood pressure to enroll.3
“Despite great progress in recent years, unmet needs still remain in the treatment of patients with metastatic non-small cell lung cancer, particularly for those without targetable biomarkers,” said Corina Dutcus, MD, senior vice president, global clinical development, oncology at Eisai Inc, in the press release.1 “[Pembrolizumab] plus [Lenvatinib] has demonstrated survival benefit in advanced renal cell carcinoma and advanced endometrial carcinoma, and while we are disappointed that the final analyses of these non-small cell lung cancer studies did not show the same benefit, we remain committed to applying learnings from these studies and furthering research in oncology for people with unmet needs. We thank all the patients, their families and the investigators involved.”
1. Merck and Eisai provide update on two phase 3 trials evaluating Keytruda® (pembrolizumab) plus Lenvima® (lenvatinib) in patients with certain types of metastatic non-small cell lung cancer. News release. September 22, 2023. Accessed September 22, 2023. https://tinyurl.com/25b7j4nm
2. Nishio M, Peled N, Zer A, et al. 1313P Phase III LEAP-006 safety run-in (Part 1): 1L pembrolizumab (Pembro) + chemotherapy (Chemo) with lenvatinib (Len) for metastatic NSCLC. Ann Oncol. 2020;31(suppl 4): S848-S849. doi:10.1016/j.annonc.2020.08.1627
3. Safety and efficacy study of pemetrexed + platinum chemotherapy + pembrolizumab (mk-3475) with or without lenvatinib (MK-7902/E7080) as first-line intervention in adults with metastatic nonsquamous non-small cell lung cancer (MK-7902-006/E7080-G000-315/LEAP-006). ClinicalTrials.gov. Updated August 23, 2022. Accessed September 22, 2023.