The OncFive: Top Oncology Articles for the Week of 2/1

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 Priority Review to Frontline Dato-DXd for Metastatic TNBC Ineligible for Immunotherapy

The FDA has accepted and granted priority review to a supplemental biologics license application seeking approval of datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) as first-line treatment for patients with unresectable or metastatic triple-negative breast cancer who are not eligible for PD-1/PD-L1 immunotherapy. The application is supported by findings from the phase 3 TROPION-Breast02 trial (NCT05374512), which showed significant improvements in overall survival (OS) and progression-free survival (PFS) with Dato-DXd (n = 323) vs investigator’s choice of chemotherapy (n = 321). The median OS in the respective arms was 23.7 months (95% CI, 19.8-25.6) and 18.7 months (95% CI, 16.0-21.8; HR, 0.79; 95% CI, 0.64-0.98; P = .0291), and the median PFS was 10.8 months (95% CI, 8.6-13.0) and 5.6 months (95% CI, 5.0-7.0; HR, 0.57; 95% CI, 0.47-0.69; P < .0001). Dato-DXd also elicited a confirmed objective response rate (ORR) of 62.5% vs 29.3% with chemotherapy (odds ratio, 4.24; 95% CI, 3.03-5.95). The Prescription Drug User Fee Act (PDUFA) target action date is planned for Q2 2026.

FDA Accepts NDA for Zanzalintinib Plus Atezolizumab in Pretreated mCRC

The FDA has accepted a new drug application for zanzalintinib (XL092) paired with atezolizumab (Tecentriq) in patients with previously treated metastatic colorectal cancer and set a PDUFA date of December 3, 2026. The submission is supported by data from the phase 3 STELLAR-303 trial (NCT05425940), which demonstrated improved OS with the zanzalintinib regimen vs regorafenib (Stivarga) in the intention-to-treat population, at a median of 10.9 months and 9.4 months, respectively (HR, 0.80; 95% CI, 0.69-0.93; P = .0045). The median PFS favored the zanzalintinib combination at 3.7 months vs 2.0 months with regorafenib, although formal statistical significance could not be claimed per hierarchical testing. Safety data were aligned with what has been reported with the known profiles, with diarrhea, hypertension, fatigue, and nausea among the most common adverse effects (AEs).

FDA Updates Axi-Cel Label to Remove Limitation of Use in R/R PCNSL

The FDA has approved an update to the prescribing information for axicabtagene ciloleucel (axi-cel; Yescarta), removing the prior Limitation of Use for patients with relapsed/refractory primary central nervous system (CNS) lymphoma (PCNSL). This decision was supported by data from an investigator-sponsored phase 1 study (NCT04608487) showing an acceptable safety profile in PSNSL, despite high rates of neurologic AEs. Grade 3 neurologic toxicities occurred in 31% of patients, and no new safety signals were identified. Axi-cel is now the only CAR T-cell therapy for relapsed/refractory large B-cell lymphoma without this CNS-related labeling restriction.

Rolling FDA BLA Submission for OST-HER2 Begins for Fully Resected Pulmonary Metastatic Osteosarcoma

OS Therapies has initiated a rolling biologics license application submission seeking FDA approval of OST-HER2 (OST31-164) to prevent or delay recurrence after complete resection of pulmonary metastatic osteosarcoma. The effort is supported by findings from a phase 2b study (NCT04974008), which showed a 2-year OS rate of 75% among evaluable patients, exceeding historical controls. Moreover, patients with event-free survival of at least 12 months achieved a 100% 2-year OS rate. The non-clinical and chemistry, manufacturing, and controls modules have already been submitted to the FDA with a request for rolling review. After an FDA invitation after a December 2025 Type C meeting, OS Therapies requested a Type D meeting to review new comparative oncology biomarker data spanning the phase 2b human trial and a parallel canine osteosarcoma study. The company anticipates submitting the clinical module by the end of March with a potential FDA action date by September 30, 2026.

FDA Grants Fast Track Designation to Pelareorep Plus Bevacizumab/FOLFIRI in Second-Line KRAS-Mutant mCRC

The FDA has granted fast track designation to pelareorep (Reolysin) in combination with bevacizumab (Avastin) and FOLFIRI (leucovorin, 5-fluorouracil [5-FU], irinotecan) for second-line treatment of KRAS-mutant, microsatellite stable metastatic colorectal cancer. The designation is supported by data from the phase 1 REO 022 study (NCT01274624), which showed an ORR of 33%, exceeding historical outcomes with bevacizumab plus chemotherapy alone. Early survival outcomes with the drug included a median PFS of 16.6 months and a median OS of 27.0 months. Translational analyses showcased the expansion of KRAS-specific T-cell populations, supporting further clinical development.