Phase III KEYNOTE-361 Trial Fails to Meet Primary End Points

June 10, 2020

The trial is evaluating pembrolizumab in combination with chemotherapy for the first-line treatment of patients with advanced or metastatic urothelial carcinoma.

An update from the phase III KEYNOTE-361 trial, evaluating pembrolizumab (Keytruda) in combination with chemotherapy for the first-line treatment of patients with advanced or metastatic urothelial carcinoma, indicated that the study did not meet its pre-specified dual primary endpoints of overall survival (OS) or progression-free survival (PFS), compared with standard of care chemotherapy (cisplatin or carboplatin plus gemcitabine), according to Merck, the agent’s developer.

Though in the final analysis of the study there was an improvement in OS and PFS for patients treated with the anti-PD-1 therapy in combination with chemotherapy alone, these results did not meet statistical significance per the pre-specified statistical plan.

“In this study, (pembrolizumab) in combination with chemotherapy in previously untreated patients with advanced or metastatic bladder cancer was rigorously tested against active control of the current standard of care chemotherapy combination regimen,” Roy Baynes, MD, PhD, senior vice president and head of global clinical development, as well as chief medical officer at Merck, said in a press release. “While we are disappointed in these study results, (pembrolizumab) has been established as an important option in the treatment of metastatic bladder cancer, and we are committed to continuing our research to help more patients with this disease. We are grateful to the patients and investigators for their participation in this study.”

In this randomized, open-label study, 1010 patients were randomized to receive either:

  • Pembrolizumab (200 mg intravenously [IV] on day 1 of each 3-week cycle for up to 35 cycles); plus cisplatin (70 mg/m2 IV) or carboplatin (AUC 5 IV or AUC 4.5 IV if required per local guidelines) on day 1 or day 2 of each 3-week cycle; plus gemcitabine (1000 mg/m2 IV) on day 1 and day 8 of each 3-week cycle
  • Pembrolizumab monotherapy (200 mg IV on day 1 of each 3-week cycle for up to 35 cycles)
  • Cisplatin (70 mg/m2 IV) or carboplatin (AUC 5 IV or AUC 4.5 IV if required per local guidelines) on day 1 or day 2 of each 3-week cycle; plus gemcitabine (1000 mg/m2 IV) on day 1 and day 8 of each 3-week cycle.

In addition to the primary endpoints, secondary endpoints include duration of response, disease control rate, overall response rate, and safety.

The monotherapy arm of the study has not yet been formally tested, as superiority was not reached for OS or PFS in the pembrolizumab combination arm. However, the safety profile of pembrolizumab observed in this trial was consistent with previously reported studies, and no new safety signals were reported.

Results from this trial will be presented at an upcoming medical meeting and will be discussed with regulatory authorities.

Pembrolizumab has already been approved by the FDA for bladder indications across multiple types and stages of bladder cancer. In addition, Merck indicated that they are continuing to evaluate pembrolizumab as a monotherapy and in combination with other anti-cancer therapies across several disease settings, such as metastatic, muscle invasive bladder cancer and non-muscle invasive bladder cancer.

Reference:

Merck Provides Update on Phase 3 KEYNOTE-361 Trial Evaluating KEYTRUDA® (pembrolizumab) as Monotherapy and in Combination with Chemotherapy in Patients with Advanced or Metastatic Urothelial Carcinoma [news release]. Kenilworth, NJ. Published June 9, 2020. mrknewsroom.com/newsroom/news-releases/news-details/2020/Merck-Provides-Update-on-Phase-3-KEYNOTE-361-Trial-Evaluating-KEYTRUDA-pembrolizumab-as-Monotherapy-and-in-Combination-with-Chemotherapy-in-Patients-with-Advanced-or-Metastatic-Urothelial-Carcinoma/default.aspx. Accessed June 10, 2020.