- Incyte Corp. continues to build a case for the combination of its IDO1 inhibitor epacadostat and Merck & Co.'s immunotherapy Keytruda, reporting new data Thursday that supports the potential for the drug pairing to deliver added benefit over Keytruda monotherapy in advanced melanoma.
- Updated results from the ECHO-202 study showed treatment with the combo led to a median progression-free survival (PFS) of 12.4 months across all 54 efficacy-evaluable patients. The overall response rate checked in at 56%, with eight complete responses.
- Analysts view IDO inhibition as complementary to suppressing the PD-1 pathway, potentially offering a better match than CTLA-4 blockers like Bristol-Myers Squibb Company's Yervoy. Yet, data in larger groups of patients is only just beginning to emerge, and it remains a challenge to separate the added benefit of IDO inhibitors from the anti-tumor activity of PD-(L)1 inhibitors.
Incyte has benefited substantially from the industry's headlong rush into testing new immuno-oncology combinations.
Both Merck and Bristol-Myers Squibb have expanded deals with the Delaware-based biotech to develop epacadostat — the most advanced IDO1 inhibitor — paired with each company's respective checkpoint inhibitor across a range of cancer types.
Those partnerships have helped to underpin growing optimism in epacadostat's clinical efficacy, sending Incyte stock rocketing upwards in value. Over the past 12 months, the biotech's share price has increased by 71%, ballooning the company's market capitalization to a lofty $27 billion.
ECHO-202, the study Incyte reported on Thursday, is a Phase 1/2 trial evaluating Keytruda (pembrolizumab) together with epacdostat across several dosing regimens and cancer types. Promising data in melanoma had previously led Merck and Incyte to push the combo into the ongoing Phase 3 ECHO-301 trial, which is set to read out in the spring of next year.
According to updated results, 30 of the 54 efficacy-evaluable experienced a response with most (22) seeing a partial response. Among the 45 treatment-naive advanced melanoma patients, the combo had nearly identical response rates, although the group receiving a 100 mg dose of epacadostat saw a slightly higher response rate of 60%.
Notably, median PFS at this data cut was 12.4 months among all patients and was not reached in treatment-naive patients. Data like that, if held up in the ECHO-301 study, could make Keytruda plus epacadostat competitive with the dominant Opdivo (nivolumab)/Yervoy (ipilimumab) pairing.
"ORR/PFS looks very competitive to Opdivo+Yervoy," wrote Cowen & Co. analyst Steve Scala in a August 31 note. "If this is replicated in Phase III, then the [Bristol-Myers]’s Opdivo+Yervoy combo will have an important new competitor."
In the Checkmate-067 study, treatment with Opdivo plus Yervoy led to a 11.5 median PFS and 50% objective response rate.
Incyte will present further updates on the ECHO-202 study at the European Society of Medical Oncology conference in early September.