Designing a Better Trial of Sintilimab in Nonsquamous NSCLC

Jorge Nieva, MD, associate professor of Clinical Medicine at the Keck School of Medicine of University of Southern California, discusses how a future clinical trial of sintilimab (Tyvyt) injection plus chemotherapy should look in order to achieve FDA approval for the treatment of patients with nonsquamous non–small cell lung cancer (NSCLC).

The supplemental biologics licenses application for sintilimab/chemotherapy for the treatment of nonsquamous NSCLC was supported with data from the phase 2 OREINT-11 clinical trials. But, during the recent meeting of the FDA’s Oncologic Drugs Advisory Committee (ODAC), members of ODAC stated that the population of patients in the ORIENT-11 study was not diverse enough to be applicable to the United States patient population.

Although Nieva voted differently than the other 14 ODAC members who voted, he agrees that if the developer were to conduct another study, the population should be more diverse and should focus on more relevant end points instead of overall or progression-free survival (PFS).

Transcription:

0:08 | We want drugs tested in ethnically diverse populations. I think it was less important for sintilimab than for some other drugs because it was a me-too drug. And because it wasn't a novel molecular entity, I think I would have been completely on board with the other groups, the rest of the group's decision making, if this had been a novel, small molecule, or something with a novel mechanism of action, but this drug was neither of those things.

0:49 | I think it's a real challenge now to ask, how would you test the drug in lung cancer in the metastatic setting, and do it in a global way with a diverse population, unless you go back into those countries that don't have access to PD-1 inhibitors and try to replicate the design.

1:15 | But I think the FDA was not happy with the design, because it was an outdated design. You know, it was a design based on the standard of care back in 2016. And not the standard of care and 2021. And I don't think you really can design something with a 2021 standard of care with a survival or a PFS endpoint anymore. I just don't think it's possible unless you go to these underserved nations that don't have access to these medications. But I don't know if that was really the goal of the discussion.