- Looking for an edge in immuno-oncology, AstraZeneca plc plans to test its checkpoint inhibitor Imfinzi together with Incyte Corp.'s experimental IDO1 blocker epacadostat in Stage 3, unresectable non-small cell lung cancer (NSCLC).
- A major clinical setback over the summer dented AstraZeneca's chances of catching market leaders Merck & Co. and Bristol-Myers Squibb and Co. in metastatic NSCLC. But strong results from a study known as PACIFIC could hand the British drugmaker an advantage in the earlier-stage lung cancer market.
- That Incyte's epacadostat is AstraZeneca's choice to pair with Imfinzi is not surprising. Both Merck and Bristol-Myers have inked major collaboration deals with the Delaware biotech, viewing IDO1 inhibition as a potentially complementary pathway to boost the response rates of PD-(L)1 blockers.
Success in PACIFIC gives AstraZeneca a chance to gain a foothold in the immuno-oncology, despite the damaging failure of the pharma's MYSTIC study.
In PACIFIC, treatment with Imfinzi (durvalumab) cut the risk of disease progression by nearly half in patients with Stage 3 lung cancers that can't be removed surgically. While most new NSCLC patients are diagnosed with metastatic disease, AstraZeneca estimates Stage 3 cancers account for roughly one-third of all NSCLC cases — with unresectable tumors representing a good portion of that population.
So far, the success of checkpoint inhibitors like Merck's Keytruda (pembrolizumab) and Bristol-Myers' Opdivo (niovlumab) has been in the metatstatic setting. PACIFIC helps to differentiate Imfinzi and could put AstraZeneca two to three years ahead of its rivals in treating earlier-stage disease, according to company estimates.
The Food and Drug Administration is currently reviewing Imfinzi for approval in the Stage 3 setting and a decision could come next spring.
Testing Imfinzi together with epacadostat, then, is aimed at building on that potential. Enrollment of the planned pivotal Phase 3 study is expected to begin in the first half of 2018 and the drugmakers will split the cost of development.
For Incyte, 2018 will be a critical year. A Phase 3 trial testing epacadostat with Merck's Keytruda in melanoma is expected to read out in the first half, and will be a key test of whether adding an IDO1 inhibitor to PD-(L1) blockade really does help more patients see a benefit from immuno-oncology.
Earlier results suggest such a boost could be there, but it's unclear how much additional benefit epacadostat delivers.
Two other pivotal studies testing epacadostat with Keytruda and Opdivo, respectively, in a variety of solid tumors are set to begin before the end of the 2017.
Spreading the risk of failure across many combo studies with different checkpoint inhibitors appears to be a core element of Incyte's strategy — and working with AstraZeneca will add another layer.
"We look forward to beginning this additional pivotal trial for epacadostat, as we seek to position IDO1 enzyme inhibition as a key component of combination immunotherapy," said Steven Stein, Incyte's chief medical officer, in a Oct. 31 statement.
Incyte also recently paid $150 million upfront to acquire rights to MacroGenics Inc.'s experimental PD-1 inhibitor MGA012, giving the biotech its own checkpoint blocker to develop in tandem with the collaboration studies for epacadostat.
All that momentum has translated into a steady build-up of Incyte's market capitalization, now sitting at an impressive $24 billion. 2018 will begin to prove whether that lofty valuation is justified.