Incyte got a boost last month when the ASCO abstract from its closely watched ECHO-202 trial of IDO1 inhibitor epacadostat and Merck's Keytruda in lung cancer went online. With the presentation of the data now completed, the overall view is still positive and backs up the potential for combining the two checkpoint inhibitor classes, according to analysts, although separate data on Incyte's combo with Bristol-Myers Squibb was a mixed bag.
The headline news in non-small cell lung cancer (NSCLC) is that the overall response rate (ORR) for epacadostat plus Keytruda stayed the same at 35%, and two patients converted from partial responses to complete responses which, according to Leerink, "incrementally strengthens [the] IDO1 thesis."
To put the numbers in context, it's about twice the ORR seen with Keytruda on its own, and according to Leerink no complete responses have previously been seen with Merck's drug as a monotherapy in this second-line NSCLC setting.
The data on the duration of response are still maturing but currently stand at 6 months, also encouraging, and the combination seemed to have an effect regardless of PD-L1 expression, suggesting it may be useful for a broad range of NSCLC patients.
One question about the data has been raised by Adam Feuerstein of TheStreet, who points out that Incyte didn't reveal data on three lung cancer patients who became eligible for evaluation after the abstract was posted, and who might have altered the response rate figure.
Incyte insisted it had done nothing wrong by omitting them, but the move was "unusual" and "provided investors a hazier view of epacadostat than necessary," says Feuerstein. The biotech's position is that it chose with Merck to include only patients who had passed a specified follow-up period since treatment.
Other data showed an extra response among a cohort of patients with renal cell carcinoma, pushing the ORR to 33% with one complete response, which, along with the NSCLC results—and earlier data in melanoma patients—suggest "responses seem to deepen over time."
Some of the other findings were less encouraging. Analysts at Jefferies noted that results in triple-negative breast cancer (TNBC) the ORR was 10% for the combination—which was "unimpressive compared to pembro alone"—and only included partial responses. Similarly, for ovarian cancer there was an ORR of 8%, all partial. And they say they are neutral on the update overall.
Importantly, however, the results showed that the PD-1/IDO1 inhibitor combination was well tolerated, which is important as side effects have emerged as an issue for combinations of PD-1 blockers and CTLA4 inhibitors and targeted tyrosine kinase inhibitor (TKI) drugs.
So far, the only non-chemotherapy, immuno-oncology combination approved for marketing is Bristol-Myers Squibb's PD-1 inhibitor Opdivo and CTLA4 inhibitor Yervoy for melanoma, and blocking IDO is viewed as potentially a more tolerable alternative to CTLA4 inhibition with potential in multiple cancers.
The epacadostat/Keytruda results "stands out among other emerging immuno-oncology ... combinations at ASCO, supportive of the planned randomized trials in our view," said the analysts.
The fact that so much attention is being paid to an early-stage trial is remarkable, but understandable given that Incyte's valuation of $27 billion rests more firmly on epacadostat's potential after Eli Lilly-partnered rheumatoid arthritis drug baricitinib was rejected by the FDA in April.
The company is moving ahead with six pivotal studies in four tumor types in collaboration with Merck, as well as two pivotal programs with BMS.
The ECHO-202 data "establish a strong basis for progressing this novel, investigational immunotherapy combination into pivotal studies for the first-line treatment of these patients," commented study investigator Tara Gangadhar, M.D., of the Hospital of the University of Pennsylvania.
Incyte also posted data from its combo with Bristol-Myers’ PD-1 Opdivo (nivolumab), rival to Keytruda, at the ASCO meeting across a number of tumor locations.
These include patients with squamous cell carcinoma of the head and neck (SCCHN), treatment-naïve advanced melanoma (MEL), ovarian cancer (OC), and colorectal cancer (CRC).
The data showed that in 40 patients with MEL treated with epacadostat plus Opdivo, the combined objective response rate (ORR) was 63%, including 2 complete responses and 23 partial responses (PRs). There was also a combined disease control rate (DCR) of 88%.
Meanwhile, in previously treated patients with SCCHN, the combined ORR was 23%, including 1 CR and 6 PRs, and the combined DCR was 61%.
“Responses for MEL and SCCHN were observed regardless of PD-L1 expression and HPV status (in SCCHN), and all responses were ongoing at the data cutoff [mid-Feb.],” the companies said in a joint statement.
But putting the two together “did not demonstrate an efficacy signal in the unselected refractory OC and CRC patient populations,” Incyte and Bristol-Myers said, a blow for these potential indications.
Incyte was down 5% by midday trading today, with Merck, which was also posting other Keytruda data at ASCO, down slightly by 0.8%.