The OncFive: Top Oncology Articles for the Week of 9/20/2026

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 Lirafugratinib for Pretreated, Locally Advanced or Metastatic Cholangiocarcinoma

The FDA has approved lirafugratinib (Lyrfigtu), a highly selective FGFR2 inhibitor, for adult patients with previously treated unresectable, locally advanced, or metastatic cholangiocarcinoma (CCA) harboring an FGFR2 gene fusion or other rearrangement. The approval was supported by the phase 1/2 REFOCUS trial (NCT04526106), in which lirafugratinib elicited an overall response rate (ORR) of 46% (95% CI, 36%-55%) and a median duration of response (DOR) of 11.8 months (95% CI, 7.5-13.0). Among 114 evaluable patients presented at the 2026 Gastrointestinal Cancers Symposium, the ORR was 46.5% (95% CI, 37.1%-56.1%) with a disease control rate (DCR) of 96.5% (95% CI, 91.3%-99.0%) and a median overall survival (OS) of 22.8 months (95% CI, 18.1-27.2), while FGFR inhibitor–naive patients (n = 11) achieved an ORR of 63.6% (95% CI, 30.8%-89.1%). In the pivotal safety population of FGFR inhibitor–naive patients with CCA (n = 116), any-grade treatment-related adverse effects (TRAEs) occurred in 100% of patients and grade 3 or higher TRAEs in 57.8%, with the most common treatment-emergent effects being nail toxicities (87.9%), palmar-plantar erythrodysesthesia syndrome (81.9%), and stomatitis (78.4%). The prescribing information includes warnings and precautions for ocular toxicity, embryo-fetal toxicity, and hyperphosphatemia and soft tissue mineralization.

FDA Approves Belzutifan Plus Lenvatinib for Advanced ccRCC

The FDA has approved belzutifan (Welireg), a hypoxia-inducible factor 2 alpha inhibitor, plus lenvatinib (Lenvima) for adult patients with advanced renal cell carcinoma with a clear cell component (ccRCC) after a PD-1 or PD-L1 inhibitor, based on the open-label, randomized, active-controlled LITESPARK-011 trial (NCT04586231). The combination significantly improved median progression-free survival (PFS) vs cabozantinib (Cabometyx), at 14.6 months (95% CI, 11.1-16.6) vs 10.6 months (95% CI, 9.2-11.1; HR, 0.74; 95% CI, 0.61-0.89; 1-sided P = .00095). Although the combination produced a numerical OS improvement (33.7 months [95% CI, 29.0-46.9] vs 28.6 months [95% CI, 24.1-31.4]; HR, 0.85; 95% CI, 0.70-1.03), the difference was not statistically significant; the ORR was 53% (95% CI, 47%-58%) with the combination vs 40% (95% CI, 35%-45%) with cabozantinib (1-sided P = .0002). Among the 747 patients randomly assigned 1:1 to the combination (n = 371) or cabozantinib (n = 376), TRAEs occurred in 97.6% of combination-treated patients, with 71.6% grade 3 or higher and 2 fatal; the most common treatment-emergent adverse effects were anemia (69.2%), hypertension (58.9%), diarrhea (52.7%), and fatigue (45.1%). The combination offers a new option in the post–immunotherapy ccRCC setting.

FDA Grants Priority Review to Perioperative Durvalumab Plus Neoadjuvant Enfortumab Vedotin in MIBC

The FDA has granted priority review to a supplemental biologics license application (sBLA) seeking approval of durvalumab (Imfinzi) plus enfortumab vedotin-ejfv (Padcev) for patients with muscle-invasive bladder cancer (MIBC) who are not candidates for or have declined cisplatin-based chemotherapy, with a Prescription Drug User Fee Act target action date set for the fourth quarter of 2026. The sBLA is supported by the phase 3 VOLGA trial (NCT04960709), in which perioperative durvalumab paired with neoadjuvant enfortumab vedotin significantly improved event-free survival (EFS) and OS vs radical cystectomy with or without approved adjuvant treatment, with no new safety signals. The trial randomly assigned 695 patients 1:1:1 to durvalumab plus enfortumab vedotin and tremelimumab (Imjudo) before surgery followed by durvalumab and tremelimumab adjuvant therapy, durvalumab plus enfortumab vedotin before surgery followed by durvalumab adjuvant monotherapy, or standard of care, with EFS for both experimental arms serving as the dual primary end point. A May 2026 interim analysis had shown a significant EFS improvement over standard of care and a favorable OS trend that was not yet statistically significant at that time. If approved, this would be the first perioperative regimen with enfortumab vedotin given only before surgery, with regulatory applications also under review in the European Union, Japan, and other countries.

Updated NCCN Guidelines Recommend Rusfertide Across Polycythemia Vera

Rusfertide (Mimrylo), a hepcidin mimetic, has been recommended as a Category 1 treatment option across both low- and high-risk polycythemia vera in the latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Myeloproliferative Neoplasms, making it the only therapy to carry a Category 1 designation across both risk groups. The inclusion is based on the phase 3 VERIFY trial (NCT05210790) and the phase 2 REVIVE trial (NCT04057040); in part 1a of VERIFY, patients who received rusfertide plus standard of care (n = 147) achieved a clinical response in 76.9% of cases vs 32.9% among those given placebo plus standard of care (n = 146) during weeks 20 to 32 (P < .0001). Rusfertide met both the primary end point and all secondary end points in VERIFY and was generally well tolerated through 52 weeks, with the most common adverse effects being injection site reactions (56%) and anemia (16%). The recommendation follows the agent's August 28, 2026, FDA approval for adults with polycythemia vera, which was also based on the REVIVE and VERIFY trials. The designation addresses a longstanding need for options that help maintain hematocrit control, which most patients treated for polycythemia vera do not currently achieve.

SOT106 Lands Dual FDA Designations for Osteosarcoma and Soft Tissue Sarcoma

The FDA has granted orphan drug designation to SOT106, an investigational antibody-drug conjugate (ADC), for soft tissue sarcoma (STS) and fast track designation for osteosarcoma — meaning the agent now holds both designations across both indications, having previously received orphan drug designation for osteosarcoma in June 2026 and fast track designation for STS in August 2026. SOT106 has not yet entered clinical testing; the designations were supported by target biology and preclinical findings, with the agent targeting leucine-rich repeat-containing 15 (LRRC15), an antigen expressed across multiple sarcoma subtypes and in tumor stroma but limited in normal adult tissue. In preclinical patient-derived xenograft models, SOT106 demonstrated antitumor activity and tolerability, including tumor regression in an LRRC15 low-expressing model of pediatric osteosarcoma where a first-generation LRRC15-targeting ADC was ineffective, along with complete responses across STS subtypes and other solid tumor models. The ADC pairs an LRRC15-directed antibody with the microtubule-disrupting agent monomethyl auristatin E via site-specific conjugation technology, releasing its payload selectively within the tumor and producing a bystander effect. SOTIO expects to initiate a first-in-human trial later in 2026, with no clinical efficacy or safety data reported to date.