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In urothelial bladder cancer patients, epacadostat was added to pembrolizumab in the ECHO-202/KEYNOTE-037 open-label, phase I/II trial.7 Patients with advanced urothelial carcinoma, prior platinum chemotherapy and no prior checkpoint inhibitor therapy were eligible to participate. A total of 40 patients were evaluated with an impressive overall response rate of 35%, with all being partial responses. The treatment was well tolerated with rash being the most common toxicity other than fatigue. Rash occurred in 18% of patients, reaching grade 3 status in 7.5% of patients. As a result, two ongoing phase 3 trials have been launched. One is the KEYNOTE-672/ECHO-307 trial for patients with advanced urothelial carcinoma who are ineligible for cisplatin chemotherapy. The other is the KEYNOTE-698/ECHO-303 trial for patients with recurrent or progressive urothelial carcinoma after receipt of prior platinum-based chemotherapy.
In renal cell carcinoma, epacadostat with pembrolizumab also achieved impressive response rates in the ECHO-202/KEYNOTE-037 trial cohort. Eligible patients had advanced clear cell renal cell carcinoma after prior antiangiogenic therapy and no prior checkpoint inhibitor therapy. A total of 33 patients were enrolled and 30 were efficacy evaluable. Overall response rates were 47% for those with 0-1 prior treatments but 0% for those with 2 or more prior treatments. Fatigue and rash were the most common adverse events. Due to the impressive response rates in the 0-1 prior treatment group, the phase 3 KEYNOTE-679/ECHO-302 trial has been launched in the first-line metastatic setting, pitting the combination of epacadostat plus pembrolizumab vs. standard of care antiangiogenic therapy, either sunitinib or pazopanib.
Please see below for brief summaries and access to the ongoing phase 3 trials in both urothelial and renal cell carcinoma.
- Pembrolizumab +/- Epacadostat for urothelial carcinoma patients previously treated with platinum chemotherapy – NCT03374488
- Pembrolizumab + Epacadostat vs. Sunitinib or Pazopanib for advanced renal clear cell carcinoma in the first line – NCT03260894
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- Smith DC, Gajewski T, Hamid O, et al. Epacadostat plus pembrolizumab in patients with advanced urothelial carcinoma: Preliminary phase I/II results of ECHO-202/KEYNOTE-037. J Clin Oncol 2017; 35: suppl; abstr 4503.
- Lara P, Bauer TM, Hamid O, et al. Epacadostat plus pembrolizumab in patients with advanced RCC: Preliminary phase I/II results from ECHO-202/KEYNOTE-037. J Clin Oncol 2017; 35: suppl; abstr 4515.