The OncFive: Top Oncology Articles for the Week of 8/30

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 Camizestrant Plus a CDK4/6 Inhibitor for Emergent ESR1-Mutated HR+, HER2– Advanced Breast Cancer

The FDA has granted accelerated approval to camizestrant (Etcamah) plus a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor (abemaciclib [Verzenio], palbociclib [Ibrance], or ribociclib [Kisqali]) for adult patients with hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer that acquires an ESR1 mutation during treatment with an aromatase inhibitor plus a CDK4/6 inhibitor, as identified by an FDA-approved companion diagnostic. The approval was supported by the phase 3 SERENA-6 trial (NCT04964934), in which patients whose circulating tumor DNA (ctDNA) signaled an emergent ESR1 mutation before radiographic progression were randomly assigned to switch to camizestrant plus their existing CDK4/6 inhibitor (n = 157) or continue an aromatase inhibitor plus CDK4/6 inhibition (n = 158). The investigator-assessed median progression-free survival (PFS) was 16.0 months (95% CI, 12.7-18.2) with the camizestrant switch vs 9.2 months (95% CI, 7.2-9.5) with continued therapy (HR, 0.44; 95% CI, 0.31-0.60; P < .00001), and the PFS benefit was sustained across PIK3CA- and TP53-co-mutated subgroups. The median time to second progression was 25.7 months (95% CI, 20.4-30.3) with camizestrant vs 19.1 months (95% CI, 16.8-21.0) with the control regimen (HR, 0.63; 95% CI, 0.46-0.86; P = .00373), and total ctDNA clearance occurred in 51.0% of camizestrant-treated patients vs 1.9% of control-treated patients, correlating with an overall survival (OS) benefit (HR, 0.39; 95% CI, 0.19-0.73). Overall survival data remained immature across all data cutoffs, and the approval follows an April 2026 Oncologic Drugs Advisory Committee vote against the clinically meaningful benefit for the ctDNA-triggered switch, after which supplementary evidence were submitted that supported the FDA’s decision.

FDA Approves Ropeginterferon Alfa-2b for Essential Thrombocythemia

The FDA has approved ropeginterferon alfa-2b-njft (Besremi) for adult patients with essential thrombocythemia (ET), making it the first new agent cleared for ET in the United States since anagrelide (Agrylin) in 1997. In the phase 3 SURPASS-ET trial (NCT04285086), ropeginterferon alfa-2b (n = 91) produced a modified European LeukemiaNet response rate of 37.4% (95% CI, 27.4%-48.1%) at months 9 and 12 vs 3.6% (95% CI, 0.8%-10.2%) with anagrelide (n = 83; P = .0001) in patients with high-risk, hydroxyurea-resistant or -intolerant ET. Ropeginterferon alfa-2b also reduced major ET-related thrombotic events and cardiovascular events vs anagrelide through month 12, alongside greater reductions in JAK2 V617F and CALR allele burden than anagrelide. Treatment-emergent adverse effects (TEAEs) of grade 3 or higher occurred in 23.1% of patients who received ropeginterferon alfa-2b vs 33.8% of those treated with anagrelide, with no fatal adverse effects (AEs) in the ropeginterferon arm compared with 3 fatal AEs with anagrelide. The approval follows the November 2021 FDA approval of ropeginterferon alfa-2b for polycythemia vera.

Daraxonrasib Yields Durable Responses in Previously Treated RAS-Mutant NSCLC

Daraxonrasib (Rasonque), an oral RAS(ON) multiselective inhibitor of GTP-bound mutant and wild-type RAS proteins, produced durable responses in patients with previously treated, advanced RAS-mutant non–small cell lung cancer (NSCLC) whose disease progressed on platinum-based chemotherapy and anti–PD-1 or anti–PD-L1 therapy, according to phase 1/2 data from the RMC-6236-001 trial (NCT05379985) published in The New England Journal of Medicine. Among 38 patients treated at 160 mg to 220 mg, daraxonrasib produced a confirmed complete or partial response in 42% (95% CI, 26%-59%) of those with any RAS mutation, with a median duration of response of 11.5 months (95% CI, 4.6-not estimable [NE]) and a median time to response of 1.4 months (range, 1.2-6.2). In this group, the median PFS was 8.3 months (95% CI, 4.0-12.5), and the median OS was 16.0 months (95% CI, 9.5-NE), with confirmed responses observed in 31% (95% CI, 14%-52%) to 37% (95% CI, 24%-52%) of patients across the 120-mg-or-less, 160-mg-to-220-mg, and 300-mg dose levels in the full safety and efficacy population (n = 136). AEs of grade 3 or higher occurred in 54% of the 136 patients in the safety population, most commonly pneumonia, diarrhea, and rash, and treatment-related AEs (TRAEs) of grade 3 or higher occurred in 30% of patients, with a single grade 4 TRAE of pneumonitis reported at the 300-mg dose. These findings support the ongoing phase 3 RASolve 301 trial (NCT06881784), which is evaluating a 200-mg dose of daraxonrasib vs docetaxel as second-line therapy for RAS-mutant NSCLC.

FDA Receives sNDA for Selinexor Plus Ruxolitinib in JAK Inhibitor–Naive Myelofibrosis

A supplemental new drug application (sNDA) has been submitted to the FDA seeking accelerated approval of selinexor (Xpovio) plus ruxolitinib (Jakafi) for JAK inhibitor–naive myelofibrosis, with priority review requested and filing acceptance expected in the fourth quarter of 2026. The sNDA is supported by the phase 3 SENTRY trial (NCT04562389), in which selinexor plus ruxolitinib met the co-primary end point of a spleen volume reduction of at least 35% (SVR35) at week 24 in 49.8% of patients (n = 235) vs 28.0% of those who received placebo plus ruxolitinib (n = 118; odds ratio, 2.58; 95% CI, 1.60-4.17; one-sided P < .0001). The trial missed its other co-primary end point of change in total symptom score from baseline at week 24, with an adjusted mean change of –9.9 with the investigational combination vs –10.9 with ruxolitinib plus placebo (adjusted mean difference, 0.97; 95% CI, –1.07 to 3.02; one-sided P = .825). Any-grade TEAEs occurred in 99.1% of patients treated with selinexor plus ruxolitinib vs 97.4% of those treated with placebo plus ruxolitinib, with grade 3 or higher TEAEs observed in 70.1% vs 50.0% of patients, respectively. The most common AEs in the selinexor arm were thrombocytopenia (59%; grade ≥ 3, 18%), anemia (57%; grade ≥ 3, 37%), and nausea (57%; grade ≥ 3, 7%). A prespecified secondary analysis showed an OS signal that favored the combination arm (HR, 0.43; 95% CI, 0.19-1.00; nominal one-sided P = .022), and in a landmark analysis, the SVR35 at week 24 predicted OS regardless of treatment arm.

FDA Grants Fast Track Designation to MT027 for Recurrent Glioblastoma

The FDA has granted fast track designation to MT027, an allogeneic, off-the-shelf B7-H3–targeted chimeric antigen receptor T-cell therapy, for the treatment of patients with recurrent glioblastoma. MT027 is administered via a locoregional intracavitary route directly into intracranial tumors and previously received FDA orphan drug designation for recurrent high-grade glioma. The therapy is being evaluated in the phase 2 GLIOMAX-101 trial (NCT07386002), an open-label study enrolling approximately 40 patients with recurrent or progressive IDH wild-type, World Health Organization grade 4 glioblastoma who have received prior standard-of-care therapy and have B7-H3–positive disease. Patients will receive intracerebroventricular MT027 at 3 × 10⁷ cells on days 1 and 15 of each 28-day cycle, following a safety run-in phase of 3 to 6 patients evaluated for dose-limiting toxicities. The primary end points are the incidence of dose-limiting toxicities during the safety run-in and the 12-month OS rate.