The OncFive: Top Oncology Articles for the Week of 4/12

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 BLA for Ifinatamab Deruxtecan in Pretreated ES-SCLC

The FDA has accepted and granted priority review to a biologics license application (BLA) seeking the approval of ifinatamab deruxtecan (I-DXd) in adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or following platinum-based chemotherapy. The BLA is supported by findings from the phase 2 IDeate-Lung01 trial (NCT05280470) and the phase 1/2 IDeate-PanTumor01 trial (NCT04145622). In the primary analysis of IDeate-Lung01, patients who received I-DXd at 12 mg/kg (n = 137) achieved a confirmed overall response rate (ORR) of 48.2% (95% CI, 39.6%-56.9%), a median duration of response (DOR) of 5.3 months (95% CI, 4.0-6.5), and a median progression-free survival (PFS) of 4.9 months (95% CI, 4.2-5.5); the estimated 9-month overall survival (OS) rate was 59.1% (95% CI, 50.4%-66.8%). Any-grade treatment-emergent adverse effects (TEAEs) occurred in 98.5% of patients; 62.0% of these effects were grade 3 or higher. The most common any-grade TEAEs included nausea (48.2%), anemia (45.3%), decreased appetite (38.7%), and neutropenia (38.0%).

FDA Approval Is Sought for Zenocutuzumab in NRG1+ Cholangiocarcinoma

A supplemental biologics license application (sBLA) has been submitted to the FDA for zenocutuzumab-zbco (Bizengri) in adult patients with advanced unresectable or metastatic cholangiocarcinoma (CCA) harboring an NRG1 gene fusion, supported by findings from the phase 1/2 eNRGy study (NCT02912949). In the CCA cohort of eNRGy, patients achieved an ORR of 36.8% (95% CI, 16.3%-61.6%) and a median DOR of 12.9 months per blinded independent central review (BICR). Concurrently, the National Comprehensive Cancer Network has added the agent to its Clinical Practice Guidelines in Oncology for biliary tract cancers as a Category 2A–recommended subsequent-line therapy and a Category 2B–recommended first-line treatment for NRG1 fusion–positive CCA. Zenocutuzumab was found to be well tolerated. “The identification of NRG1 gene fusions has highlighted an actionable biomarker, and the eNRGy study data suggest that targeted inhibition with zenocutuzumab may represent a meaningful treatment approach for these patients,” James Cleary, MD, PhD, of Dana-Farber Cancer Institute, stated in a news release.

Daraxonrasib Yields Significant Survival Advantages vs Chemotherapy in Metastatic Pancreatic Cancer

Findings from the first interim analysis of the phase 3 RASolute 302 trial (NCT06625320) showcased that daraxonrasib (RMC-6236) significantly improved OS vs standard-of-care cytotoxic chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma, with all PFS and OS end point data from this analysis considered final. In the intention-to-treat (ITT) population, those given daraxonrasib experienced a median OS of 13.2 months vs 6.7 months with chemotherapy (HR, 0.40; P <.0001). Daraxonrasib was generally well tolerated with a manageable toxicity profile and no new safety signals. Revolution Medicines announced plans to submit these findings in a new drug application (NDA) to the FDA and other global regulatory agencies. Data are also planned for presentation at the 2026 ASCO Annual Meeting.

First-Line Darovasertib Plus Crizotinib Yields PFS Benefit in Metastatic Uveal Melanoma

Darovasertib (IDE196) paired with crizotinib (Xalkori) led to a statistically significant PFS improvement over investigator’s choice of ipilimumab (Yervoy) plus nivolumab (Opdivo; n = 78) or pembrolizumab (Keytruda; n = 25) in patients with HLA-A*02:01–negative metastatic uveal melanoma, meeting the primary end point of the phase 2/3 OptimUM-02 trial (NCT05987332). Patients who received darovasertib plus crizotinib (n = 210) experienced a median PFS of 6.9 months by BICR vs 3.1 months with investigator’s choice of treatment (n = 103; HR, 0.42; 95% CI, 0.30-0.59; P <.0001). The ORRs with the respective approaches were 37.1% and 5.8% (P <.0001); the median DOR with the combination was 6.8 months. OS data were immature at the time of the top-line analysis, although an early trend favored the darovasertib arm. The combination was found to have a manageable safety profile consistent with prior reports. The most common grade 3 or higher TEAEs were syncope, hypertension, and diarrhea. IDEAYA Biosciences plans to submit an NDA to the FDA in the second half of 2026 seeking accelerated approval of darovasertib plus crizotinib in this indication.

Emactuzumab Improves ORR, Functional Outcomes in Tenosynovial Giant Cell Tumor

The phase 3 TANGENT trial (NCT05417789) met its primary and secondary end points. Emactuzumab (RG-7155) led to statistically significant improvements in ORR per RECIST 1.1 criteria and tumor volume score (TVS) vs placebo at 6 months in adult patients with tenosynovial giant cell tumor (TGCT). The agent also provided clinically meaningful improvements in patient-reported outcomes, including physical function per the Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) measure, pain, range of motion, and stiffness. Benefits were rapidly achieved, durable, and consistent, spanning clinically relevant patient subgroups, with a manageable toxicity profile consistent with previous clinical experience. Prior phase 1 (NCT01494688) data in 63 patients with diffuse-type TGCT had shown an ORR of 71% with the agent across all dose levels, with 82% of responses occurring within 3 months. SynOx Therapeutics plans to submit a BLA to the FDA in the second half of 2026 seeking approval of emactuzumab for TGCT, with a European Union marketing authorization application to follow.