The OncFive: Top Oncology Articles for the Week of 8/3

Welcome to OncLive®’s OncFive!

Every week, we bring you a quick roundup of the 5 top stories from the world of oncology—ranging from pivotal regulatory decisions to key pipeline updates to expert insights on breakthroughs that are moving the needle in cancer care. This resource is designed to keep you informed on the latest updates in the space, in just a matter of minutes.

Here’s what you may have missed this week:

FDA Grants Accelerated Approval to Zongertinib for Nonsquamous NSCLC With HER2 TKD Mutations

The FDA granted accelerated approval to zongertinib (Hernexeos) for adults with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain–activating mutations, as detected by an FDA-approved test, following prior systemic therapy. The decision was supported by data from the phase 1 Beamion LUNG-1 trial (NCT04886804), which evaluated zongertinib monotherapy in patients with HER2-altered advanced NSCLC. Among those previously treated with platinum-based chemotherapy but no HER2-targeted TKI or antibody-drug conjugate (ADC; n = 71), the ORR was 75% with a 6-month duration of response (DOR) rate of 58%; patients who also had prior HER2-targeted ADC exposure (n = 34) achieved an ORR of 44% and a 6-month DOR rate of 27%. Most treatment-related adverse effects were grade 1 or 2, with diarrhea (51%) and rash (27%) being the most common. No cases of treatment-related interstitial lung disease were reported. The agent is also being investigated in the phase 3 Beamion LUNG-2 trial (NCT06151574) against standard-of-care therapy in this patient population.

FDA Approves Dordaviprone for Diffuse Midline Glioma

The FDA granted accelerated approval to dordaviprone (Modeyso) for adult and pediatric patients aged 1 year or older with H3K27M-mutant diffuse midline glioma and progressive disease after prior therapy, marking the first systemic therapy approved in this setting. The decision was supported by pooled data from 50 patients treated with the monotherapy across 5 open-label, nonrandomized US trials: ONC006 (NCT02525692), ONC013 (NCT03295396), ONC014 (NCT03416530), ONC018 (NCT03134131), and ONC016 (NCT05392374). The overall response rate was 22% with a median duration of response of 10.3 months; 73% of responders maintained responses for at least 6 months, and 27% maintained responses for at least 12 months. The median time to response was 8.3 months. A 50% or greater corticosteroid dose reduction occurred in 46.7% of evaluable patients (n = 7/15), and performance score improvements occurred in 20.6% of evaluable patients (n = 6/34). The most common grade 3 treatment-related or -emergent adverse effect was fatigue (10%). Prescribing information includes warnings for QTc prolongation, hypersensitivity, and embryo-fetal toxicity.

FDA Grants Priority Review to Liso-Cel for R/R Marginal Zone Lymphoma

The regulatory agency has granted priority review to a supplemental biologics license application seeking approval of lisocabtagene maraleucel (liso-cel; Breyanzi) for use in adults with relapsed/refractory marginal zone lymphoma (MZL) after at least 2 prior lines of systemic therapy. The submission is supported by findings from the MZL cohort of the phase 2 TRANSCEND FL trial (NCT04245839), in which efficacy-evaluable patients (n = 66) achieved an ORR of 95.5% and a complete response rate of 62.1%. At a median follow-up of approximately 2 years, the 24-month DOR rate was 88.6%, the progression-free survival (PFS) rate was 85.7%, and the overall survival rate was 90.4%. No new safety signals were reported. Any-grade cytokine release syndrome (CRS) occurred in 76% of patients, with 4% experiencing grade 3 events; no grade 4/5 cases occurred. If approved, liso-cel could become the first CAR T-cell therapy standardized for use in this disease.

FDA Accepts NDA for New Formulation of PSMA PET Imaging Agent Piflufolastat F 18 in Prostate Cancer

The FDA has accepted a new drug application seeking approval of a reformulated version of piflufolastat F 18 (Pylarify; formerly 18F-DCFPyL-PET/CT), a prostate-specific membrane antigen (PSMA) PET imaging agent, for use in patients with prostate cancer. The Prescription Drug User Fee Act target action date is March 6, 2026. This formulation is designed to improve manufacturing efficiency, increasing batch size by approximately 50% and enhancing radioactive concentration, which could expand patient access. Piflufolastat F 18 is indicated for PET of PSMA in patients with suspected metastasis who are candidates for initial definitive therapy, and for those with suspected disease recurrence based on elevated prostate-specific antigen levels. The submission is supported by data from the phase 3 CONDOR trial (NCT03739684), in which the imaging agent achieved correct localization rates of 84.8% to 87.0% and led to changes in intended management for 63.9% of patients with biochemically recurrent prostate cancer. If approved, the new formulation could strengthen Lantheus’ leadership in PSMA-targeted prostate cancer imaging by enabling broader and more efficient diagnostic access.

Epcoritamab Plus Rituximab and Lenalidomide Hits Both Primary End Points in R/R Follicular Lymphoma

The phase 3 EPCORE FL-1 trial (NCT05409066) showed that adding epcoritamab-bysp (Epkinly) to rituximab (Rituxan) and lenalidomide (Revlimid) significantly improved ORR and PFS compared with rituximab and lenalidomide alone in patients with relapsed/refractory follicular lymphoma, meeting both coprimary end points. In a preplanned interim analysis, the triplet reduced the risk of death or disease progression by 79% (HR, 0.21; P < .0001) and significantly improved ORR (P < .0001). Based on these results, the FDA accepted a supplemental biologics license application for the triplet in this setting, granting it priority review with a Prescription Drug User Fee Act target action date set for November 30, 2025. The safety profile was consistent with that of the individual agents, and no new safety signals emerged. Additional data from EPCORE FL-1 will be presented at the 2025 ASH Annual Meeting and support global regulatory submissions.

Honorable Mention: The FDA has approved the intravenous (IV) formulation of tocilizumab-anoh (Avtozma), a biosimilar to IV tocilizumab (Actemra), for treating severe or life-threatening CRS induced by CAR T-cell therapy in adults and pediatric patients aged 2 years and older.