WCLC: Merck analyses throw doubt on new biomarker's utility

Merck rolled out retrospective analyses on two Keytruda-combo trials in first-line lung cancer at WCLC. (Merck)

Looking to find their niche in the ultra-lucrative non-small cell lung cancer market, some immuno-oncology companies have turned to investigational biomarker TMB, or tumor mutational burden, in hopes of ID’ing patient populations for whom their treatments might be more effective.

But lung cancer behemoth Merck is throwing cold water on that idea. Sunday at the World Conference on Lung Cancer in Barcelona, the New Jersey drugmaker rolled out results from two exploratory analyses showing that “there does not appear to be a role” for TMB in determining which patients are most likely to benefit from its market-leading Keytruda-chemo combo.

RELATED: In a monster showing, Merck's Keytruda combo slashes lung cancer death risk by half

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The pharma giant compiled TMB data from patients in its phase 2 Keynote-021 study and its phase 3 Keynote-189 study, both of which examined I-O star Keytruda in tandem with chemo in previously untreated NSCLC patients. In both trials, the combo performed consistently across patients with various levels of TMB, and Merck didn’t find a significant correlation between TMB and the combo’s ability to provoke patient responses, delay disease progression or prolong survival.

In short, “it turns out that the results are really unaffected by TMB status,” Roy Baynes, M.D., Merck SVP and head of global clinical development, said. Keynote-189, which cemented the Keytruda-chemo combo as regimen to beat in first-line lung cancer, is “an important data set,” and the new exploratory results “will help provide quite good guidance” to academic physicians who are “obviously very intrigued by the TMB question,” he noted.

The findings are good news for Merck, as they “establish very clearly that all patients who can tolerate chemotherapy” should receive the Keytruda pairing in the front-line setting, Baynes said.

But for companies that have sought to establish TMB as a way to segment the population, it’s not a great sign. And unfortunately for those companies, they haven’t had many good signs to point to in the last year.

RELATED: The skeptics were right: Bristol-Myers has pulled a crucial Opdivo lung filing as it awaits more data

In January, Bristol-Myers Squibb withdrew its Opdivo-Yervoy application in first-line lung on grounds that it needed more data to show the pairing produced better results in TMB-high patients than it did in the rest of the population. And in August, AstraZeneca said an I-O combination of Imfinzi and candidate tremelimumab had struck out in TMB-high patients with stage 4 metastatic NSCLC when pitted against standard-of-care chemo.

“The idea that you could somehow select patients better for alternative therapies or other strategies based upon TMB–these data don’t support that,” Baynes said of Merck’s new results.

That’s not to say the case is closed on TMB’s role in therapy selection. “We think TMB is an important area to study, and we are studying it,” Baynes said.

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