Phase 3 studies of pembrolizumab fail to meet key survival endpoints
Phase 3 studies of pembrolizumab — with chemotherapy for metastatic castration-resistant prostate cancer and with lenvatinib for unresectable liver cancer — did not meet primary endpoints of survival, according to the agent’s manufacturer.
Pembrolizumab, (Keytruda, Merck), an anti-PD-1 antibody, has been approved as monotherapy and in combination with other therapies for patients with a variety of cancers.
KEYNOTE-921 data
The double-blind, randomized phase 3 KEYNOTE-921 trial assessed pembrolizumab among men with chemotherapy-naive metastatic castration-resistant prostate cancer whose disease progressed or exhibited intolerance to a next-generation hormonal therapy.
Researchers randomly assigned the 1,030 study participants to pembrolizumab dosed at 200 mg every 3 weeks for up to 2 years in combination with docetaxel and prednisone or placebo plus docetaxel and prednisone.
OS and radiographic PFS served as primary endpoints. Secondary endpoints included PSA response rate, time to start of first subsequent anticancer treatment, objective response rate and duration of response.
The study showed “modest trends” toward longer OS and radiographic PFS among those who received the pembrolizumab regimen, but the results did not meet statistical significance according to the pre-specified statistical plan, according to a Merck press release.
“Results from this study serve as an important reminder that metastatic prostate cancer remains very difficult to treat, and more research is needed,” Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer of Merck Research Laboratories, said in the release. “We will continue to advance our clinical development program to evaluate Keytruda-based combinations and novel candidates for patients with this disease.”
LEAP-002 data
The multicenter, double-blind, randomized phase 3 LEAP-002 trial assessed pembrolizumab with the multiple receptor tyrosine kinase inhibitor lenvatinib (Lenvima, Eisai) vs. lenvatinib alone as first-line treatment of adults with unresectable hepatocellular carcinoma. The trial is part of the LEAP (lenvatinib and pembrolizumab) clinical program, through which Merck and Eisai are evaluating the treatment combination in a dozen tumor types across more than 15 clinical trials, according to a Merck press release.
Lenvatinib received FDA approval in 2018 as monotherapy for first-line treatment of patients with unresectable HCC, based on findings of the phase 3 REFLECT trial.
“Aiming for further improvement in the treatment of patients with unresectable HCC, we selected Lenvima monotherapy, a standard of care option, as the control arm of the LEAP-002 trial,” Corina Dutcus, MD, senior vice president of clinical research in oncology at Eisai Inc., said in the press release.
Investigators randomly assigned 794 patients enrolled in LEAP-002 in a 1:1 ratio to receive lenvatinib dosed at 12 mg orally once daily (8 mg for patients with a screening body weight of less than 60 kg) until disease progression or unacceptable toxicity plus either pembrolizumab dosed at 200 mg via IV on day 1 of every 3-week cycle for up to 35 cycles or saline placebo.
PFS, assessed by blinded independent central review per modified RECIST version 1.1 and OS served as dual primary endpoints. Secondary endpoints included ORR and duration of response.
Although the study showed trends toward improved OS and PFS among those who received the combination regimen, the results did not meet statistical significance according to the pre-specified statistical plan, the press release stated. The lenvatinib monotherapy group has longer median OS than reported in prior trials of the agent alone in unresectable HCC.
Safety results of the combination appeared consistent with previous reports.
Merck and Eisai intend to present data from LEAP-002 at a future medical meeting, according to the press release.
References:
- Merck and Eisai provide update on phase 3 LEAP-002 trial evaluating Keytruda (pembrolizumab) plus Lenvima (lenvatinib) versus Lenvima monotherapy in patients with unresectable hepatocellular carcinoma. Available at: www.merck.com/news/merck-and-eisai-provide-update-on-phase-3-leap-002-trial-evaluating-keytruda-pembrolizumab-plus-lenvima-lenvatinib-versus-lenvima-monotherapy-in-patients-with-unresectable-hepatocellul/. Published Aug. 3, 2022. Accessed Aug. 3, 2022.
- Merck provides update on phase 3 KEYNOTE-921 trial evaluating Keytruda (pembrolizumab) plus chemotherapy in patients with metastatic castration-resistant prostate cancer. Available at: www.merck.com/news/merck-provides-update-on-phase-3-keynote-921-trial-evaluating-keytruda-pembrolizumab-plus-chemotherapy-in-patients-with-metastatic-castration-resistant-prostate-cancer/. Published Aug. 3, 2022. Accessed Aug. 3, 2022.