On Thursday, Roche unveiled positive results from its first-line lung-cancer combo trial—but those results raised more questions than they provided answers.
Adding PD-L1 drug Tecentriq to a combination of Avastin and chemo reduced the risk of disease worsening or death by 38% compared with Avastin and chemo alone, Roche said. Those who received Tecentriq alongside the duo went a median 8.3 months before their disease worsened, compared with 6.8 months in the Avastin-chemo-only group.
Thirty-seven percent of patients also reached the one-year mark without their cancer progressing—more than double the 18% of Avastin-chemo patients who hit that same benchmark.
Investors and analysts are still waiting on several key pieces of information, though—some of which they’re hoping to get tonight when full results of the study, dubbed IMpower150, are presented at the European Society for Medical Oncology’s Immuno-Oncology Congress in Geneva, Switzerland.
One of those pieces: just what Roche meant when it said Thursday morning that early overall survival results from the trial looked “encouraging.” Leerink Partners analyst Seamus Fernandez wrote to clients that he’s also “hopeful” Roche will present the outcome of adding just Avastin to chemo, to be compared with the result of adding just Tecentriq to chemo.
There's also the question raised by a biomarker that markedly improved the results in Tecentriq patients. That group saw their risk of worsening disease or death slashed by half.
The answers to those questions have far-reaching consequences, as four drugmakers—Roche and rivals Merck, Bristol-Myers Squibb and AstraZeneca—are all gunning for prime combo positioning in the mammoth first-line lung cancer market. So far, Merck is the only one with an FDA nod for those patients; AstraZeneca’s CTLA-4 combo has posted a progression-free survival miss, while Bristol-Myers’ data is still forthcoming, thanks to a delay.
The TEFF biomarker could make a big difference, one analyst said; a subgroup with that particular gene signature saw their risk of disease worsening or death plummet by 49% after receiving the Tecentriq-Avastin-chemo trio. “At first blush, the findings look good,” Bernstein’s Tim Anderson, M.D., wrote in his investor note. But “the important data that is missing is whether TEFF is only a proxy for PD-L1 status, or whether it is something totally different,” he said, adding that “actual data proving” that they are different “are not shown.”
Previous trials have indicated that the PD-1/L1 immunotherapies are most effective in patients expressing high levels of the PD-L1 biomarker.
As for how Roche’s data stacks up against Merck’s—tested alongside chemo rather than a CTLA-4 drug—they look “good but not better” than the New Jersey drugmaker’s, Evercore ISI analyst Umer Raffat wrote in a note to clients. Merck scored its chemo-combo approval for Keytruda earlier this year after posting strong progression-free survival numbers in a phase 2 study, and it also boasts a monotherapy indication for Keytruda in the front-line setting for patients with high levels of PD-L1.
Fernandez agreed; the way he sees it, “Merck’s Keytruda is unlikely to be displaced by Tecentriq plus Avastin in PD-L1 high patients,” he said.
Of course, when it comes to pitting these results aganst Merck’s phase 2 study, it’s a “flawed comparison,” as Anderson cautioned. That study, known as Keynote-021G, was much smaller, and data from its phase 3 trial, Keynote-189, aren’t yet available.
“IMpower150 is one important piece of a complex, still largely incomplete, puzzle,” Anderson wrote.