The OncFive: Top Oncology Articles for the Week of 11/8

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 Pimicotinib for Symptomatic TGCT

The FDA approved pimicotinib (Pimjetmi), a highly selective colony-stimulating factor 1 receptor inhibitor, for patients with symptomatic tenosynovial giant cell tumor (TGCT) in whom surgical resection could potentially worsen functional limitations or cause severe morbidity. The decision was supported by the randomized phase 3 MANEUVER trial (NCT05804045), in which pimicotinib (n = 63) produced an overall response rate (ORR) by blinded independent central review (BICR) of 76.2% (95% CI, 63.8%-86.0%). The BICR-assessed ORR per tumor volume score was 74.6% (95% CI, 62.1%-84.7%), and the median duration of response (DOR) was not reached (range, 0.03-19.81 months). The most common adverse effects (AEs), occurring in at least 20% of patients, were pruritus, rash, face edema, periorbital edema, fatigue, nausea, headache, and peripheral edema. Patients in MANEUVER received pimicotinib at 50 mg once daily or placebo, with placebo-arm patients permitted to switch to pimicotinib after 24 weeks, and the agent joins pexidartinib (Turalio) and vimseltinib (Romvimza) as a systemic option for TGCT.

NDA Submission Completed for Zipalertinib Plus Chemotherapy in Frontline EGFR Exon 20 Insertion–Positive NSCLC

Taiho Oncology completed a new drug application (NDA) submission to the FDA under the Real-Time Oncology Review program for zipalertinib plus platinum-based chemotherapy in patients with previously untreated, locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. The application is based on the phase 3 REZILIENT3 trial (NCT05973773), in which the median progression-free survival (PFS) by BICR was 14.5 months (95% CI, 12.9-21.4) with zipalertinib plus chemotherapy (n = 140) vs 8.5 months (95% CI, 7.0-10.9) with chemotherapy alone (n = 139; hazard ratio [HR], 0.50; 95% CI, 0.34-0.73; P = .00015). The ORR was 65.0% (95% CI, 56.49%-72.86%) vs 40.3% (95% CI, 32.06%-48.94%; P < .0001), the PFS benefit was observed in patients with (HR, 0.38; 95% CI, 0.21-0.67) and without (HR, 0.62; 95% CI, 0.38-0.99) baseline brain metastases, and overall survival (OS) data were immature (HR, 0.72; 95% CI, 0.42-1.23). Grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 80.7% of patients in the zipalertinib arm vs 40.4% in the chemotherapy arm, AEs led to zipalertinib discontinuation in 17.1% of patients, and treatment-related deaths occurred in 3 patients (2.1%), all due to sepsis or septic shock. A Prescription Drug User Fee Act (PDUFA) target action date will be assigned if the FDA accepts the filing, and a separate NDA for zipalertinib in previously treated EGFR exon 20 insertion–positive NSCLC, supported by the phase 1/2 REZILIENT1 trial (NCT04036682), has a target action date of February 27, 2027.

FDA Accepts sNDA for Gedatolisib in PIK3CA-Mutated, HR+, HER2– Advanced Breast Cancer

The FDA accepted a supplemental new drug application (sNDA) for gedatolisib (Revtorpyk) plus fulvestrant (Faslodex), with or without palbociclib (Ibrance), for adult patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer that progressed during or after at least 1 line of endocrine therapy for metastatic disease, and set a PDUFA target action date of June 25, 2027. The sNDA is supported by the PIK3CA-mutated cohort (Study 2) of the phase 3 VIKTORIA-1 trial (NCT05501886), in which gedatolisib plus palbociclib and fulvestrant (gedatolisib triplet; n = 155) produced a median PFS by BICR of 11.1 months (95% CI, 9.0-16.7) vs 5.6 months (95% CI, 5.2-7.4) with alpelisib (Piqray) plus fulvestrant (n = 155; adjusted HR, 0.50; 95% CI, 0.37-0.68; P < .0001). Gedatolisib plus fulvestrant (gedatolisib doublet; n = 52) yielded a median PFS of 11.3 months (95% CI, 9.1-22.1; adjusted HR vs alpelisib plus fulvestrant, 0.51; 95% CI, 0.33-0.79; P = .0013) in an analysis outside the hierarchical primary efficacy analysis, and ORRs were 48.9% with the triplet, 35.7% with the doublet, and 26.0% with alpelisib plus fulvestrant. Stomatitis occurred in 61.4% of patients receiving the triplet (grade 3, 16.3%) vs 34.2% of those receiving alpelisib plus fulvestrant (grade 3, 5.3%), whereas hyperglycemia occurred in 15.0% vs 57.9%, and TRAEs led to discontinuation in 2.6%, 3.8%, and 7.1% of patients in the triplet, doublet, and alpelisib arms, respectively. Gedatolisib was approved by the FDA on July 14, 2026, for the same population without a detectable PIK3CA mutation based on VIKTORIA-1 Study 1, and it is also being evaluated in the first-line setting in the phase 3 VIKTORIA-2 trial (NCT06757634).

Detalimogene Voraplasmid Responses Improve With Longer Follow-Up in BCG-Unresponsive NMIBC Ahead of BLA Submission

Updated data from pivotal cohort 1 of the phase 1/2 LEGEND trial (NCT04752722) showed improved complete response (CR) rates and durability with longer follow-up for the nonviral gene therapy detalimogene voraplasmid (EG-70) in patients with high-risk, BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ, with or without concomitant papillary disease. As of the October 29, 2026, data cutoff, the CR rate at any time was 56% (95% CI, 47%-65%) among efficacy-evaluable patients (n = 120), and the 12-month landmark CR rate (n = 110) was 24% (95% CI, 16%-33%), up from 54% and 13%, respectively, at the April 2026 analysis. The Kaplan-Meier estimate of a DOR of at least 12 months was 43% (95% CI, 30%-55%), the median duration of CR was 10.1 months (95% CI, 7.5-not estimable), and 97% of efficacy-evaluable patients were free from progression to muscle-invasive or metastatic disease, with 86% remaining free from cystectomy. Among safety-evaluable patients (n = 125), 59% experienced at least 1 TRAE, mostly grade 1 or 2, with grade 3 TRAEs in 4%, serious TRAEs in 2%, no grade 4 or 5 TRAEs, and TRAE-related discontinuation in 1% of patients. Following a pre–biologics license application (BLA) meeting with the FDA, enGene Therapeutics expects to initiate the BLA submission for detalimogene in BCG-unresponsive NMIBC by the end of 2026 and complete it in the first half of 2027, with cohort 1 data forming the basis of the application.

CHMP Recommends Belzutifan Plus Lenvatinib for Advanced ccRCC After PD-(L)1 Inhibition

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of belzutifan (Welireg) plus lenvatinib (Lenvima) for adult patients with advanced renal cell carcinoma with a clear cell component (ccRCC) following a programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. The opinion was based on the phase 3 LITESPARK-011 trial (NCT04586231), which enrolled 747 patients with ccRCC whose disease progressed on or after anti–PD-1/PD-L1 therapy; at the first interim analysis, the median PFS was 14.6 months (95% CI, 11.1-16.6) with the combination (n = 371) vs 10.6 months (95% CI, 9.2-11.1) with cabozantinib (Cabometyx; n = 376; HR, 0.74; 95% CI, 0.61-0.89; 1-sided P = .00095). The PFS benefit was maintained at the second interim analysis (HR, 0.70; 95% CI, 0.59-0.84; P = .00007), although OS, the other dual primary end point, did not reach statistical significance at the final analysis (HR, 0.85; 95% CI, 0.70-1.03); the combination also produced a higher ORR (53.1% vs 40.2%) and a longer median DOR (22.0 vs 11.9 months). Grade 3 or higher treatment-emergent adverse effects (TEAEs) occurred in 84.1% vs 82.7% of patients, TEAEs led to discontinuation of all study drugs in 11.1% vs 11.3%, and anemia (69.2% vs 25.6%) and hypoxia (15.4% vs 0%) were more frequent with belzutifan plus lenvatinib. The European Commission will now review the CHMP recommendation, with a final decision expected within 2 months, and the FDA approved belzutifan plus lenvatinib for the same ccRCC population in September 2026.