(Melanoma) Efficacy of Epacadostat + Keytruda?

• August 10, 2019
• Reading time: 2 minutes

On June 17, 2019, Georgina V. Long published results in The Lancet Oncology from the ECHO-301/KEYNOTE-252 Phase III clinical trial comparing the oral IDO1 inhibitor epacadostat plus the anti-PD-1 antibody Keytruda (pembrolizumab) versus placebo plus Keytruda in patients with unresectable or metastatic malignant melanoma.

The ECHO-301/KEYNOTE-252 trial enrolled patients with unresectable or metastatic malignant melanoma (N=706) at multiple international sites in a 1:1 placebo-controlled randomized Phase III design.

• Epacadostat combination arm: epacadostat 200 mg twice daily + Keytruda 200 mg every 3 weeks (N=354)
• Placebo combination arm: placebo + Keytruda 200 mg every 3 weeks (N=352)

This trial was initiated following evidence that immune checkpoint inhibitors have meaningful activity in melanoma, and based on Phase 1/2 ECHO-202/KEYNOTE-037 data showing favorable antitumor activity of epacadostat + Keytruda in melanoma patients.

Results at a median follow-up of 12.4 months:

Progression-Free Survival (Primary Endpoint): Median PFS was 4.7 months in the epacadostat arm versus 4.9 months in the placebo arm. There was no significant difference in progression risk between the two arms (hazard ratio 1.00).

Overall Survival (Primary Endpoint): Median OS was not reached in either arm. There was no significant difference in survival risk between the two arms (hazard ratio 1.13).

Safety: Grade ≥3 adverse events occurred in 4% (N=14) of the epacadostat arm versus 3% (N=11) in the placebo arm. Serious adverse events occurred in 10% (N=37) of the epacadostat arm versus 9% (N=32) in the placebo arm. No patients died due to treatment-related adverse events.

Based on the ECHO-301/KEYNOTE-252 trial results, Georgina V. Long and colleagues concluded that epacadostat plus Keytruda did not significantly prolong progression-free survival compared with placebo plus Keytruda in patients with unresectable or metastatic melanoma. These results clearly demonstrate that IDO1 inhibition does not enhance the efficacy of anti-PD-1 therapy.

Source: Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study (Lancet Oncol. 2019 Jun 17. pii: S1470-2045(19)30274-8. doi: 10.1016/S1470-2045(19)30274-8.)

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