FDA’s Oncologic Drugs Advisory Committee Casts Interesting Votes

On May 20, 2025, the FDA convened a meeting of the Oncologic Drugs Advisory Committee (ODAC) to consider 2 important questions. The first addressed the application for full approval of glofitamab-gxbm (Columvi) for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). The second addressed the application for the monoclonal antibody daratumumab (Darzalex) for adult patients with high-risk smoldering myeloma (SM). The FDA granted accelerated approval in 2023 to glofitamab for treatment of R/R DLBCL based on a single-arm trial that demonstrated an overall response rate of 56%. STARGLO (NCT04408638) was the confirmatory trial that, if positive, would lead to a full approval of glofitamab. In the phase 3 STARGLO trial, patients with R/R DLBCL were assigned to receive glofitamab plus gemcitabine and oxaliplatin (GemOx) or rituximab (Rituxan; Genentech) plus GemOx. The results favored glofitamab-GemOx, which demonstrated improved overall survival (OS), progression-free survival (PFS), complete response rates, and overall response rate. Although these results suggest glofitamab should be a slam dunk for full FDA approval, there is, of course, a rub. The rub is that only 25 of the 274 patients in STARGLO were from North America, whereas 131 patients, or 48%, were from Asia. Furthermore, on subset analysis, the North American patients did not benefit from glofitamab-GemOx. The FDA convened the ODAC meeting to answer the question of whether the STARGLO population and trial results are applicable to the proposed US patient population. The ODAC voted 8-to-1 that the answer is no. The FDA’s message is loud and clear: A drug may not get approved if the trial does not include enough patients from the US. Pharma, take note. T he second question addressed by ODAC was more straightforward: “Should we approve this drug?” They considered whether the results of the phase 3 AQUILA (NCT03301220) trial support a favorable benefit-risk profile for daratumumab in high-risk SM. Patients treated with daratumumab had improved PFS and OS; however, OS results were immature. The ODAC voted 6-to-2 in favor of daratumumab’s benefit/risk profile in SM. I find this a bit surprising. What really matters clinically is whether such a treatment can prevent morbidity and/or prolong OS. It will be interesting to see what the FDA decides—and what our patients prefer.