The OncFive: Top Oncology Articles for the Week of 5/3

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 Approves Zenocutuzumab for NRG1 Fusion+ Cholangiocarcinoma

The FDA has cleared zenocutuzumab-zbco (Bizengri) for the treatment of adult patients with NRG1 fusion–positive advanced, unresectable, or metastatic cholangiocarcinoma (CCA) who have experienced disease progression on or following previous systemic therapy. The decision was supported by data from the single-arm phase 1/2 eNRGy trial (NCT02912949). In 19 evaluable patients with NRG1 fusion–positive CCA, zenocutuzumab elicited an objective response rate (ORR) of 36.8% (95% CI, 16.3%-61.6%) by blinded independent central review (BICR), with a duration of response (DOR) ranging from 2.8 to 12.9 months. The approval was facilitated through the FDA's national priority voucher pilot program. Key safety considerations include infusion-related reactions (IRRs), interstitial lung disease/pneumonitis, and left ventricular dysfunction, with the most common adverse effects (AEs) including diarrhea, musculoskeletal pain, fatigue, nausea, and IRRs. Zenocutuzumab has also been added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for biliary tract cancers as a Category 2A–recommended subsequent-line therapy and Category 2B–recommended first-line therapy for NRG1 fusion–positive CCA.

FDA Approves Companion Diagnostic for Vepdegestrant in ESR1+, ER+/HER2-Negative Advanced Breast Cancer

The FDA has approved the Guardant360 CDx liquid biopsy test as a companion diagnostic for vepdegestrant (Veppanu) in patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer harboring ESR1 mutations, allowing identification of eligible patients via a noninvasive blood-based test. The decision follows the FDA approval of vepdegestrant, which happened on May 1, 2026, and was supported by findings from the phase 3 VERITAC-2 trial (NCT05654623), in which patients with ESR1-mutated disease who were given vepdegestrant (n = 136) experienced a median progression-free survival (PFS) of 5.0 months (95% CI, 3.7-7.4) vs 2.1 months (95% CI, 1.9-3.5) with fulvestrant (Faslodex; n = 134; HR, 0.57; 95% CI, 0.42-0.77; P = .0001), with confirmed ORRs of 19% (95% CI, 12%-27%) vs 4% (95% CI, 1.6%-10%), respectively. Serious AEs occurred in 9% of vepdegestrant-treated patients (n = 312), and included fracture (1.3%), hepatic injury (0.6%), and prolonged QTc (0.3%). AEs led to permanent discontinuation in 2.9% of patients, dose interruptions in 14%, and dose reductions in 1.9%; AEs proved fatal for 1.0% of patients.

FDA Accepts sNDA for Taletrectinib in ROS1+ NSCLC

The FDA has accepted a supplemental new drug application (sNDA) seeking approval of taletrectinib (Ibtrozi) in TKI-naive and TKI-pretreated patients with advanced ROS1-positive non–small cell lung cancer (NSCLC), with a target action date of January 4, 2027, incorporating an additional 10 months of data from the pivotal phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials. At the data cutoff date of August 2025, TKI-naive patients in TRUST-I (n = 103) had a median DOR of 49.7 months (95% CI, 41.3-not reached [NR]) and a median PFS of 49.6 months (95% CI, 34.5-NR). A pooled analysis presented at the 2026 AACR Annual Meeting showed a confirmed ORR of 89.8% (95% CI, 84.0%-94.1%) and an intracranial ORR (IC-ORR) of 76.5% (95% CI, 50.1%-93.2%) in TKI-naive evaluable patients (n = 157), with a median PFS of 46.1 months (95% CI, 31.8-NR) and median overall survival (OS) that was not reached (95% CI, 47.8-NR). The toxicity profile was consistent with previous reports, with no new documented AEs. Two confirmatory phase 3 trials are ongoing: TRUST-III (NCT06564324) comparing taletrectinib with crizotinib (Xalkori) in ROS1 TKI–naive patients, and TRUST-IV (NCT07154706) examining taletrectinib as adjuvant therapy in patients with resected early-stage ROS1-positive NSCLC.

Gedatolisib-Based Combinations Beat Alpelisib-Based SOC in PIK3CA-Mutant HR+ Breast Cancer

Topline data from the phase 3 VIKTORIA-1 trial (NCT05501886) showed that gedatolisib (PF-05212384) in combination with fulvestrant (Faslodex) and palbociclib (Ibrance) significantly improved PFS vs alpelisib (Piqray) plus fulvestrant in patients with PIK3CA-mutant, hormone receptor–positive, HER2-negative advanced breast cancer who had progressed on or following previous CDK4/6 inhibitor therapy combined with an aromatase inhibitor. Gedatolisib plus fulvestrant also showed a statistically significant and clinically meaningful PFS improvement vs alpelisib plus fulvestrant, although this comparison was not part of the primary hierarchical testing sequence. Both gedatolisib-based regimens were generally well tolerated with manageable toxicity profiles and no new safety signals identified. Celcuity plans to submit an sNDA to the FDA based on these data, with full results to be shared at the 2026 ASCO Annual Meeting. Separately, an NDA for gedatolisib in PIK3CA wild-type hormone receptor–positive, HER2-negative advanced breast cancer is already under FDA priority review with a Prescription Drug User Fee Act goal date of July 17, 2026, based on previously reported wild-type cohort data from VIKTORIA-1.

Daraxonrasib Monotherapy Elicits Meaningful Responses in Previously Treated, RAS-Mutated Pancreatic Cancer

Data from the phase 1/2 RMC-6236-001 trial (NCT05379985), published in the New England Journal of Medicine, showed that daraxonrasib (RMC-6236) had antitumor activity and a manageable toxicity profile across RAS mutations in 168 patients with previously treated RAS-mutated pancreatic ductal adenocarcinoma (PDAC). In patients with RAS G12-mutated PDAC receiving 300 mg as second-line therapy (n = 26), the ORR was 35% (95% CI, 17%-56%), the median DOR was 8.2 months (95% CI, 3.8-not evaluable [NE]), the median PFS was 8.5 months (95% CI, 6.7-10.5), and the median OS was 13.1 months (95% CI, 10.9-NE); among all RAS-mutated patients in the second-line setting (n = 38), the ORR was 29% (95% CI, 15%-46%), the disease control rate was 95% (95% CI, 82%-99%), the median PFS was 8.1 months (95% CI, 5.9-10.1), and the median OS was 15.6 months (95% CI, 10.9-NE). Treatment-related AEs were reported in 96% of patients, with the most common being rash (90%; grade 3 or higher, 7%), stomatitis or mucositis (54%; 4%), and diarrhea (52%; 4%) at the 300-mg dose; no treatment-related deaths were reported. Full RASolute 302 data are planned for presentation at the 2026 ASCO Annual Meeting. Revolution Medicines has announced plans to submit an NDA under the FDA Commissioner's National Priority Voucher pilot program and is examining daraxonrasib in three additional phase 3 registrational trials, including RASolute 303 (NCT07491445) in the first-line PDAC setting.

Honorable Mentions

• The ESMO Breast Cancer Congress is underway. OncLive asked leading breast oncologists to share the presentations and conversations at the top of their lists. Sign up to access exclusive insights from Sarah Sammons, MD, Paolo Tarantino, MD, PhD, and Sara M. Tolaney, MD, MPH.
• In an exclusive preview ahead of the 2026 ASCO Annual Meeting (ASCO 2026), Eric K. Singhi, MD, Isabel Preeshagul, DO, MBS, and Jonathan W. Lee, MD, MSc, spotlighted the top presentations anticipated in the field of lung cancer.
• In another exclusive preview, VK Gadi, MD, PhD, Erika Hamilton, MD, FASCO, Kevin Kalinsky, MD, MS, FASCO, and Alexis LeVee, MD, shed light on the triple-negative breast cancer presentations that are among the most anticipated datasets at ASCO 2026.
• OncLive also spoke with Yara Abdou, MD, MSCR, Jane L. Meisel, MD, FASCO, and the aforementioned breast cancer experts about the top expected updates in hormone receptor–positive and HER2-positive breast cancer at ASCO 2026.