ODAC Panel Backs Proposed Jemperli Studies
FDA’s Oncologic Drugs Advisory Committee (ODAC) has voted 8 to 5 that GlaxoSmithKline’s proposals for two single-arm clinical trials of its Jemperli (dostarlimab) are sufficient to characterize its benefits and risks in the curative intent setting for patients with locally advanced, treatment-naïve, mismatch-repair deficient or microsatellite-instability-high rectal cancer.
In advance of the meeting, FDA released a briefing document that indicated the agency was asking for ODAC input on the company’s “unprecedented use of clinical complete response rate as the major endpoint to support an approval in oncology, the trial designs that serve as the basis of a future application, and the limitations of data to inform the implementation of the proposed non-operative management strategy.”
In voting yes, University of Colorado Cancer Center’s Christopher Lieu said he did not think a randomized study is feasible based on existing data and patients’ overall goals and expectations. Lieu said he was concerned about the use of complete clinical response at 12 months as the definitive endpoint primarily because there was not a clear correlation between this and disease-free survival and distant metastasis rate. “I do think the endpoint of event-free survival at three years, which is a secondary endpoint of the study, will be critically important just to show that correlation. But overall, I believe that the studies as designed will provide the data needed for accelerated approval.”
University of South Florida’s Evangelia Katsoulakis, who voted no, said she would like to see GSK use three-year event-free survival as the primary endpoint instead of a complete clinical response at 12 months “because it is a more meaningful mark for these patients.” She also said relying on the 12-month complete clinical response is not a high enough bar for accelerated approval because there could be an efficacy issue later down the road, pointing out the difficulties in walking back an accelerated approval and the “subsequent sort of follow up that kind of goes by the wayside” in those situations.
University of Southern California’s Jorge Nieva, who voted yes, believed the data from the studies will be sufficient, but he questioned whether the data analysis will be sufficient. “There's going to be variability in the biomarker and we're going to be defining the enrolled population down to the eligible population, and I think potentially misinterpreting the data that we get,” he said. “We’re not going to be liberal in the radiographic definitions of what is persistent disease, and we're going to be very strict about that, and because of that we make this study less valid to the external world if it’s interpreted that way.”