The OncFive: Top Oncology Articles for the Week of 6/22

June 28, 2025

The FDA grants approval to Dato-DXd in EGFR+ NSCLC, revumenib sNDA is under priority review for NPM1-mutant AML, and more from OncLive this week.

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 Dato-DXd for EGFR+ NSCLC**

The FDA has granted accelerated approval to datopotamab deruxtecan (Dato-DXd; Datroway) for adults with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) who have progressed on prior EGFR-targeted therapy and platinum-based chemotherapy. The decision was supported by pooled data from the phase 2 TROPION-Lung05 (NCT04484142) and phase 3 TROPION-Lung01 (NCT04656652) trials, in which Dato-DXd showed an overall response rate (ORR) of 45% and a median duration of response of 6.5 months. The agent is administered every 3 weeks at 6 mg/kg, with precautions noted for ILD/pneumonitis, stomatitis, and ocular toxicities. Across studies, the most common low-grade adverse effects (AEs) included stomatitis, alopecia, and nausea, with grade 3 or higher treatment-related AEs occurring in 23% of patients. This marks the second FDA approval for Dato-DXd, which previously received authorization for use in metastatic hormone receptor–positive, HER2-negative breast cancer.

**FDA Grants Priority Review to Revumenib for Relapsed/Refractory NPM1-Mutant AML**

The FDA has granted priority review to a supplemental new drug application seeking approval of revumenib (Revuforj) for the treatment of patients with relapsed or refractory NPM1-mutant acute myeloid leukemia (AML); the action date has been set for October 25, 2025. This decision is based on data from the phase 1/2 AUGMENT-101 trial (NCT04065399) and is being conducted under the regulatory agency’s Real-Time Oncology Review program. Among 77 efficacy-evaluable patients, revumenib achieved a complete response (CR)/CR with partial hematologic (CRh) recovery rate of 26.0%, an ORR of 48.1%, and a median overall survival (OS) of 4.8 months, with notably longer survival (23.3 months) among those achieving CR/CRh. Most patients had received multiple prior therapies, including venetoclax (Venclexta) and FLT3 inhibitors. The treatment was generally well tolerated, with fewer than 5% discontinuing due to treatment-related AEs.

Q3 2025: 10 FDA Decisions to Watch in the Realm of Oncology

As Q2 2025 concludes, a surge of FDA oncology approvals has spotlighted major shifts toward personalized and immunologically driven treatments. Key wins included the first dual checkpoint inhibitor regimen with nivolumab (Opdivo)/ipilimumab (Yervoy) in hepatocellular carcinoma and the full approval of larotrectinib (Vitrakvi) for NTRK fusion–positive cancers. Telisotuzumab vedotin-tllv (Emrelis) became the first c-MET–targeted therapy in NSCLC, while penpulimab-kcqx, avutometinib/defactinib (Avmapki Fakzynja Co-pack), belzutifan (Welireg), and retifanlimab -dlwr (Zynyz) advanced histology-specific precision oncology in rare and difficult-to-treat malignancies. Looking ahead, Q3 is poised for further transformation with 10 closely watched FDA decisions spanning NSCLC, multiple myeloma, lymphoma, glioma, and more. These upcoming actions could significantly redefine treatment algorithms across both solid tumors and hematologic malignancies. Sign up to access the full resource.

Zanzalintinib Plus Atezolizumab Boosts OS in Previously Treated, Non–MSI-H mCRC

The combination of zanzalintinib (XL092) and atezolizumab (Tecentriq) significantly improved OS compared with regorafenib (Stivarga) in patients with previously treated, non–microsatellite instability–high metastatic colorectal cancer, according to topline data from the phase 3 STELLAR-303 trial (NCT05425940). The OS benefit was observed in the trial’s intention-to-treat population, with safety findings consistent with the known profiles of both agents and no new safety signals reported. This represents the first positive pivotal readout for zanzalintinib, a third-generation oral TKI targeting VEGF, MET, AXL, and RET. Additional OS data in the subgroup of patients without liver metastases are expected in a future final analysis. Full trial results will be presented at an upcoming medical meeting and discussed with regulatory authorities.

**NCCN Guidelines Now Recommend Taletrectinib for ROS1+ NSCLC**

The NCCN Clinical Practice Guidelines for Non–Small Cell Lung Cancer now list taletrectinib (Ibtrozi) as a preferred option for first-line and subsequent treatment of advanced ROS1-positive NSCLC, including in patients with brain metastases and ROS1 resistance mutations. These updates follow the FDA’s June 2025 approval of taletrectinib based on phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) data, which demonstrated ORRs of up to 90% in treatment-naive patients and robust intracranial activity. The guidelines recommend taletrectinib both as initial therapy and in settings of limited or multiple progression and specifically recognize its use in patients with symptomatic central nervous system disease and the ROS1 G2032R resistance mutation. A pooled analysis of the trials showed high intracranial response rates and durable benefit in both TKI-naive and -pretreated patients. These additions reflect a broader shift away from immunotherapy or chemotherapy in this molecularly defined NSCLC population.