The OncFive: Top Oncology Articles for the Week of 9/6

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 Sevabertinib for Advanced HER2 TKD–Mutated Nonsquamous NSCLC

The FDA has granted accelerated approval to sevabertinib (Hyrnuo) for use in adult patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors harbor HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test. The decision was supported by findings from the open-label, single-arm, multicenter phase 1/2 SOHO-01 trial (NCT05099172), in which treatment-naive evaluable patients (n = 69) experienced an overall response rate (ORR) of 75% (95% CI, 64%-85%), with 73% of responders achieving a duration of response (DOR) of at least 6 months and 38% achieving a DOR of at least 12 months. This decision expands the agent’s November 2025 accelerated approval, which covered patients who had received previous systemic therapy. The most common treatment-related adverse effects (AEs) were diarrhea (84%), rash (51%), stomatitis (26%), paronychia (22%), and anemia (22%), which were mainly grade 1 or 2.

FDA Extends Review Period for Zanzalintinib Plus Atezolizumab NDA in Pretreated mCRC

The FDA has extended its review period for the new drug application (NDA) seeking approval of zanzalintinib (XL092) in combination with atezolizumab (Tecentriq) for the treatment of adult patients with previously treated metastatic colorectal cancer (mCRC), moving the Prescription Drug User Fee Act target action date to March 3, 2027. This announcement follows the submission of updated data deemed to be a major amendment. The NDA is supported by results from the phase 3 STELLAR-303 trial (NCT05425940), which met its dual primary end point of significantly improved overall survival (OS) with the combination (n = 451) vs regorafenib (Stivarga; n = 450) in the intention-to-treat (ITT) population. The median OS was 10.9 months and 9.4 months, respectively (HR, 0.80; 95% CI, 0.69-0.93; P = .0045). The median progression-free survival (PFS) in the ITT population was 3.7 months with the combination vs 2.0 months with regorafenib (HR, 0.68; 95% CI, 0.59-0.79), although statistical significance could not be formally claimed under the hierarchical testing strategy. Among the 901 patients randomly assigned 1:1 to the combination or regorafenib, any-grade TRAEs occurred in 95% vs 92% of patients, respectively, and serious TRAEs occurred in 26% vs 10% of patients. The proposed indication covers patients previously exposed to fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, and, if RAS wild-type, anti-EGFR therapy.

Durvalumab Plus Tarlatamab Boosts Survival as First-Line ES-SCLC Maintenance

The addition of tarlatamab-dlle (Imdelltra) to durvalumab (Imfinzi) significantly improved OS and PFS compared with durvalumab alone when given as first-line maintenance in patients with extensive-stage small cell lung cancer (ES-SCLC) who did not progress after induction durvalumab plus platinum chemotherapy and etoposide, according to the planned interim analysis of the phase 3 DeLLphi-305 trial (NCT06211036). The combination also significantly improved ORR vs monotherapy, with a toxicity profile consistent with the individual agents and no new safety signals reported. These findings build on the phase 1b DeLLphi-303 trial (NCT05361395), in which tarlatamab plus anti–PD-L1 therapy as frontline maintenance (n = 88) led to a median OS of 25.3 months (95% CI, 20.3-not evaluable [NE]) and a median PFS of 5.6 months (95% CI, 3.5-9.0). Durvalumab is already approved as first-line maintenance for ES-SCLC based on data from the phase 3 CASPIAN trial (NCT03043872) and for limited-stage SCLC based on results from the phase 3 ADRIATIC trial (NCT03703297).

Namodenoson Generates Longer-Than-Anticipated OS Advanced HCC

Blinded OS outcomes spanning the entire patient population in the ongoing phase 3 LIVERATION trial (NCT05201404) examining namodenoson in patients with advanced hepatocellular carcinoma (HCC) appeared longer than originally anticipated based on the study’s design assumptions. Because the observed outcomes reflect the pooled, blinded population—including both namodenoson- and placebo-treated patients—conclusions about treatment efficacy or between-arm differences cannot be drawn at this time. Can-Fite BioPharma is evaluating an earlier timing for the trial’s planned interim analysis to allow an independent OS assessment aligned with the statistical analysis plan. LIVERATION is a multicenter, randomized, double-blind, placebo-controlled trial assessing namodenoson vs placebo in patients with advanced HCC and underlying Child-Pugh class B7 cirrhosis whose disease progressed on at least frontline therapy. Patients are randomly assigned 2:1 to oral namodenoson at 25 mg or matching placebo twice daily. Namodenoson is a small, orally bioavailable molecule that binds with high affinity and selectivity to the A3 adenosine receptor. The agent has received orphan drug designation in the United States and Europe, as well as FDA fast track designation as a second-line treatment for HCC.

Arlo-Cel Meets ORR End Point in BCMA-Pretreated, Quadruple-Class Exposed R/R Myeloma

Arlocabtagene autoleucel (arlo-cel; BMS-986393), a potential first-in-class autologous GPRC5D-directed CAR T-cell therapy, elicited a statistically significant and clinically meaningful ORR in adult patients with quadruple-class exposed relapsed/refractory multiple myeloma who had received 4 or more previous lines of therapy, meeting the primary end point of the registrational phase 2 QUINTESSENTIAL trial (NCT06297226). The study also met its key secondary end points of complete response (CR) rate in this population, as well as ORR and CR rate in quadruple-class exposed patients who had received 3 or more prior lines of therapy. Quadruple-class exposure was defined as prior treatment with an immunomodulatory inhibitor, a proteasome inhibitor, an anti-CD38 therapy, and a BCMA-targeted therapy. QUINTESSENTIAL is the first pivotal trial to examine a therapy in quadruple-class exposed relapsed/refractory multiple myeloma following prior BCMA-targeted therapy. The safety profile of arlo-cel was consistent with that of other CAR T-cell therapies and other GPRC5D-targeting therapies in multiple myeloma. Full results will be shared at an upcoming medical meeting.