Early Keytruda combo data paint Incyte’s epacadostat as a threat to Bristol-Myers’ I-O melanoma franchise

Incyte hopes epacadostat can boost the effect of Keytruda by stopping tumors from evading the immune system.

Incyte has presented data suggesting its IDO1 enzyme inhibitor dials up the effect Keytruda has on advanced melanoma patients. The interim phase 1/2 readout paints the Incyte-Merck combination as a potential improvement over Bristol-Myers Squibb’s incumbent CTLA-4-PD-1 cocktail.

As of late February, 54 patients in the advanced melanoma group of the epacadostat-Keytruda trial were evaluable. The overall response rate clocked in at 56%—which broke up into eight complete and 22 partial responses—and the median progression-free survival (PFS) was 12.4 months. The responses occurred regardless of the PD-L1 and BRAF mutation status of the patients.

Incyte also has evidence the responses are durable. All bar two of the 30 responses to the drug combination are still ongoing.


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The data lend credence to Incyte’s belief in the mechanism of action of epacadostat. Tumors upregulate the IDO1 enzyme to evade the immune system. Epacadostat inhibits this enzyme to dial down this evasion, helping the immune system to hit the tumor with its full force. While more data are needed to confirm the hypothesis, that could have implications for the tussle for the immuno-oncology market.

Incyte’s data stack up well against the combination of Bristol-Myers’ Opdivo and Yervoy, which won FDA approval at the start of last year on the strength of a PFS of 11.5 months in patients with advanced melanoma. 

There are reasons to think the slight difference between the PFS results from the clinical trials will ultimately translate into an edge for Incyte. Bristol-Myers’ trial enrolled treatment-naive patients, whereas some subjects in the Incyte study have previously been treated. Incyte’s treatment-naive subpopulation is yet to reach a median PFS but the rates achieved at six, 12 and 18 months suggest it is on track to better the Opdivo-Yervoy result.

Incyte can also point to safety data to argue its combination could better that of Bristol-Myers. The latest update reported 17% of patients suffered grade three or worse treatment-related adverse events. That compares favorably to results generated by Bristol-Myers’ combination, which, in an update earlier this year, was linked to a 58% rate of grade three or four adverse events.

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