Racing in lung cancer again (or still), Merck and BMS expand Incyte combo trials

Opdivo
Bristol-Myers Squibb said it would step up testing of its PD-1 immunotherapy Opdivo alongside Incyte's popular cancer partner, epacadostat.

When Bristol-Myers Squibb announced Opdivo’s big lung cancer trial miss last fall, it talked up Plan B: relying on Opdivo-based combos to expand in NSCLC. Since then, the company has inked or expanded a bevy of partnerships to test Opdivo cocktails in lung cancer and beyond.

And so have its competitors.

For a prime example, look no further than Incyte, the Wilmington, Delaware-based biotech that’s the belle of the immuno-oncology ball. On Friday, Merck & Co. said it had broadened a development deal with Incyte to test Opdivo’s top rival, Keytruda, alongside Incyte’s IDO1 inhibitor epacadostat. Merck would take the lead on developing the combo in a range of disease types, with first-line trials in non-small cell lung cancer, bladder cancer, kidney cancer and head and neck cancer.

On Sunday, Bristol-Myers said it, too, had expanded its Incyte partnership. In addition to moving the combination of Opdivo and epacadostat into two phase 3 trials in NSCLC, the partners will add new cohorts to an ongoing melanoma study.

RELATED: The top 15 best-selling cancer drugs in 2022—Opdivo

Meanwhile, Incyte has teamed up with Roche on Tecentriq combo studies, and with AstraZeneca on combining epacadostat with durvalumab, the U.K. drugmaker’s as-yet-unapproved PD-L1 inhibitor that would be fifth to market.

As for the fourth-to-market Bavencio (avelumab), approved in late March, Incyte CEO Hervé Hoppenot told Endpoints that his company is “open to” working with Merck KGaA and Pfizer, too.

It’ll be 2018 before the pivotal data starts coming out of these trials, with Merck’s Keytruda-plus-epacadostat in advanced melanoma the first up. But as ubiquitous as the names Opdivo and Keytruda have become—and as large as their sales have grown—they’re really only babies in commercial terms, with approvals just over two years old. Tecentriq is even younger, with a 2016 approval; Bavencio is an infant; and durvalumab prenatal, with a due date sometime in the second quarter of this year.

RELATED: The top 15 best-selling cancer drugs in 2022—Keytruda

The PD-1/PD-L1 checkpoint class is also under study with other types of cancer fighters, such as CTLA-4 meds; Opdivo and BMS’ CTLA-4 drug Yervoy is just one example of that cocktail type. The list of others is long and includes PARP inhibitors like Tesaro’s newly approved Zejula (niraparib) and older drug classes such as EGFR, MEK and BRAF inhibitors.

Bristol-Myers said earlier this year that it wouldn’t pursue an accelerated approval for its Opdivo-plus-Yervoy combo in melanoma, raising questions about the PD-1/CTLA-4 combination approach. Some say it’s possible that the IDO1 add-on could be more promising, including Bernstein analyst Tim Anderson, who sized up the IDO1 field in a January note to investors.

Follow-up data presented at last fall’s European Society for Medical Oncology meeting showed Keytruda-plus-epacadostat delivered responses in melanoma similar to those seen with Opdivo-plus-Yervoy, Anderson said, but with “lower toxicity.” Results in other small groups of patients with cancers of the lung and kidney, among others, also suggested favorable response-rate comparisons, he added.

“If these findings were to be replicated in phase 3 trials, CTLA-4-containing regimens could ultimately find themselves relegated to the margins because of their greater toxicity,” Anderson posited.

Of course, that’s a big “if,” as Anderson knows—in fact, as anyone who’s followed the development of any drug class knows. Early-stage data doesn’t always predict late-stage success. That’s why PD-1 and PD-L1 drugmakers are testing so many different combinations: to see which will stick.

RELATED: Top 15 pharma companies by 2016 revenue

It’s also about the race. The first of each combo type to succeed in each cancer type will have a debut commercial advantage, at least for awhile. Which is why it pays to keep an eye on the immunotherapy partnerships cropping up every week, and their pivotal trial calendars. 

Which takes us back to lung cancer. In Sunday’s announcement, Bristol-Myers said Opdivo’s epacadostat combo trials in first-line NSCLC would start this year. About Keytruda’s epacadostat cocktail on Friday, Merck said it would be “moving forward with multiple phase 3 studies in these four additional tumor types as quickly as possible,” and those four include first-line NSCLC. Anderson put a finer point on it; he said the goal is to begin this year. Stay tuned.