The Targeted Pulse: FDA’s ODAC Meetings Make Waves Across Oncology

ODAC Votes STARGLO Trial Not Applicable to US Patients With DLBCL

On Tuesday, May 20, 2025, the FDA's Oncologic Drug Advisory Committee (ODAC) voted 8-1 that results from the STARGLO trial (NCT04408638) of glofitamab-gxbm (Columvi) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) are not applicable to the US patient population. The trial, designed as a confirmatory study for an already accelerated-approved drug, had a disproportionately low US enrollment (9%) compared with Asian regions (48%). ODAC members expressed concern that the limited US data, coupled with regional differences in efficacy and patient characteristics (e.g., age, transplant eligibility reasons), made it impossible to confidently extrapolate the positive overall survival (OS) and progression-free survival (PFS) findings to US patients. The committee emphasized the need for sufficient US representation in clinical trials to ensure generalizability and robust data for regulatory decisions.

ODAC Votes Daratumumab Benefits Smoldering MM

Also on Tuesday, the ODAC voted 6-2 to support subcutaneous daratumumab (Darzalex Faspro) for patients with high-risk smoldering multiple myeloma (SMM), a precursor to multiple myeloma. Despite concerns about the trial's demographic representation, including low Black patient enrollment, and the immaturity of OS data, the committee acknowledged daratumumab's significant improvement in PFS, delaying the onset of full-blown multiple myeloma. Proponents highlighted the high risk of progression in patients with SMM and the potential to prevent debilitating symptoms, viewing SMM as a malignancy. Dissenting votes raised questions about the benefit-risk balance of treating asymptomatic patients, the precision of risk stratification, and the long-term impact of earlier intervention.

FDA ODAC Votes 4 to 5 Against UGN-102 for Recurrent LG-IR-NMIBC

On Wednesday, May 21, 2025, in a narrow 5-4 vote, the ODAC deemed the benefit-risk profile of UGN-102 (intravesical mitomycin) unfavorable for patients with recurrent low-grade, intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). While UGN-102 showed a high complete response rate in the single-arm ENVISION trial (NCT05243550), ODAC and FDA concerns centered on the lack of a randomized comparative trial to assess the durability of response against the natural disease course or standard treatments like transurethral resection of bladder tumors (TURBT). The committee also cited issues with the prematurely terminated ATLAS trial (NCT04688931), a lack of long-term data on subsequent treatments, and uncertainties regarding UGN-102's real-world impact on reducing repeated TURBTs and overall safety compared with existing care.

ODAC Rejects Label Expansion for Talazoparib in Non-HRRm mCRPC

Also on Wednesday, the ODAC voted 8-0 against expanding the indication of talazoparib (Talzenna) plus enzalutamide (Xtandi) to include all patients with metastatic castration-resistant prostate cancer (mCRPC) who do not have homologous recombination repair mutations (non-HRRm). Although the TALAPRO-2 trial (NCT03395197) showed an OS benefit in the unselected population, the committee expressed significant concerns. They highlighted the lack of a prespecified, statistically powered analysis for the non-HRRm subgroup, which comprises most patients with mCRPC. This absence, coupled with increased hematologic toxicity and inconsistencies with other PARP inhibitor trials, led the ODAC to conclude that the benefit-risk profile for this broader population was not sufficiently favorable.