The OncFive: Top Oncology Articles for the Week of 9/27/2026

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 Pirtobrutinib for Previously Untreated CLL/SLL

The FDA approved pirtobrutinib (Jaypirca) for adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with no known 17p deletion. The approval was supported by findings from the phase 3 BRUIN CLL-313 trial (NCT05023980), in which, at an estimated median follow-up of 28 months, median progression-free survival (PFS) was not estimable (NE; 95% CI, NE-NE) with pirtobrutinib (n = 141) vs 33.5 months (95% CI, 32.7-NE) with bendamustine plus rituximab (Rituxan; n = 141; HR, 0.20; 95% CI, 0.11-0.37; P < .0001). The overall response rates (ORRs) were 94% (95% CI, 89%-98%) vs 81% (95% CI, 73%-87%), and the complete response (CR) rates were 13% vs 21% with pirtobrutinib vs bendamustine plus rituximab, respectively. The overall survival (OS) data trended in favor of pirtobrutinib at a median OS follow-up of 32.2 months (HR, 0.257; 95% CI, 0.070-0.934; P = .0261), with 24-month OS rates of 97.8% (95% CI, 93.3%-99.3%) vs 93.0% (95% CI, 87.0%-96.3%). The most common non-laboratory, any-grade adverse effects (AEs) in at least 20% of patients receiving pirtobrutinib were upper respiratory tract infections (27%), rash (22%), and COVID-19 (21%). The most common grade 3 or 4 laboratory abnormality was decreased neutrophil count, and serious AEs occurred in 28% of patients. BRUIN CLL-313 randomly patients (n = 282) 1:1 to receive pirtobrutinib at 200 mg once daily until progression or to bendamustine plus rituximab for up to 6 cycles, with 18 patients in the control arm crossing over to receive pirtobrutinib at progression. The prescribing information for pirtobrutinib carries warnings for infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity.

FDA Grants Priority Review to Elinzanetant for Endocrine Therapy–Associated Vasomotor Symptoms in HR+ Breast Cancer

The FDA has granted priority review to a supplemental new drug application (sNDA) seeking approval of elinzanetant (Lynkuet) for moderate-to-severe vasomotor symptoms in patients receiving endocrine therapy for the management or prevention of hormone receptor–positive breast cancer. In the phase 3 OASIS-4 trial (NCT05587296), elinzanetant at 120 mg (n = 316) reduced the mean daily frequency of moderate-to-severe vasomotor symptoms by 6.51 events at week 4 vs 3.04 events with placebo (n = 158; least squares [LS] mean difference, −3.5; 95% CI, −4.4 to −2.6; P < .0001) and by 7.76 vs 4.20 events at week 12 (LS mean difference, −3.4; 95% CI, −4.2 to −2.5; P < .0001). A treatment effect favoring elinzanetant emerged as early as week 1 and continued through week 12. Patients who switched from placebo to elinzanetant had similar reductions, and vasomotor symptom severity improved numerically with elinzanetant vs placebo (mean change from baseline, −0.73 vs −0.43 at week 4 and −0.98 vs −0.53 at week 12). During the 12-week placebo-controlled period, treatment-emergent adverse effects (TEAEs) occurred in 69.8% of patients receiving elinzanetant (n = 315) vs 62.0% of those receiving placebo (n = 158), most commonly somnolence (10.8%), headache (9.5%), fatigue (9.5%), arthralgia (6.3%), and nausea (6.0%), with serious TEAEs in 2.5% vs 0.6% of patients, respectively. Over the full 52 weeks of the study, any-grade TEAEs occurred in 79.1% of patients who received elinzanetant (n = 465), and serious TEAEs were reported in 7.1% of patients. Elinzanetant, a dual neurokinin-1 and neurokinin-3 receptor antagonist, was approved by the FDA in October 2025 at 60 mg for moderate-to-severe hot flashes due to menopause based on the phase 3 OASIS-1 (NCT05042362), OASIS-2 (NCT05099159), and OASIS-3 (NCT05030584) trials.

Tabelecleucel BLA Is Resubmitted to FDA for EBV+ Post-Transplant Lymphoproliferative Disease

Pierre Fabre Pharmaceuticals has resubmitted a biologics license application (BLA) to the FDA seeking approval of tabelecleucel (Ebvallo) monotherapy for adult and pediatric patients at least 2 years with Epstein-Barr virus (EBV)–positive post-transplant lymphoproliferative disease (PTLD) who have been treated with 1 or more prior therapies. The third submission, which follows 2 complete response letters (CRLs), is based on alignment reached at an April 2026 Type A meeting with the FDA and includes updated data with additional patients and longer follow-up from the pivotal, single-arm phase 3 ALLELE trial (NCT03394365), along with supplemental data from expanded access programs, a separate clinical study, and commercial experience in Europe. In ALLELE data presented at the 2024 American Society of Hematology Annual Meeting and Exposition, tabelecleucel (n = 75) produced an ORR of 50.7% (95% CI, 38.9%-62.4%) in EBV-positive PTLD after rituximab progression, with a CR rate of 28.0%, a median duration of response (DOR) of 23.0 months (95% CI, 12.1-NE), and a median OS of 18.4 months (95% CI, 6.9-NE). Serious TEAEs were reported in 62.7% of patients, including 8.0% TEAEs that were considered related to tabelecleucel. Fatal TEAEs occurred in 19.2% of patients who received hematopoietic cell transplant and 18.4% of those who received solid organ transplant, none considered treatment-related, with no cases of tumor flare, infusion-related reactions, cytokine release syndrome, or immune effector cell–associated neurotoxicity syndrome reported. The FDA issued a first CRL in January 2025 over observations at a third-party manufacturing facility, accepted a resubmitted BLA with priority review in July 2025, and issued a second CRL in January 2026 stating that the single-arm ALLELE study no longer sufficed to support accelerated approval, before agreeing that a single-arm study with a prespecified historical control could support a future BLA.

Savolitinib Plus Osimertinib NDA Submitted to FDA for MET-Driven, EGFR-Mutated NSCLC After EGFR TKI

A new drug application (NDA) has been submitted to the FDA seeking approval of savolitinib (Orpathys) plus osimertinib (Tagrisso) for locally advanced or metastatic non–small cell lung cancer (NSCLC) with MET overexpression or amplification whose disease progressed on or after treatment with an EGFR TKI. The submission is supported by the global phase 3 SAFFRON trial (NCT05261399; n = 338), in which savolitinib plus osimertinib significantly improved PFS and OS vs platinum-based doublet chemotherapy in patients with EGFR-mutated NSCLC with MET overexpression or amplification whose disease progressed on osimertinib. In the phase 3 SACHI trial (NCT05015608) that supported the approval of the agent for this indication in China, the investigator-assessed median PFS in patients with EGFR-mutated, MET-amplified NSCLC after EGFR TKI failure was 8.2 months (95% CI, 6.9-11.2) with savolitinib plus osimertinib (n = 106) vs 4.5 months (95% CI, 3.0-5.4) with pemetrexed plus platinum chemotherapy (n = 105; HR, 0.34; 95% CI, 0.23-0.49; P < .0001). The safety profile of the combination in SAFFRON was consistent with the known profiles of each agent with no new safety concerns, although AE rates have not been reported, while in SACHI, grade 3 or higher TEAEs occurred in 57% of patients in both the savolitinib/osimertinib arm (n = 60/106) and the chemotherapy arm (n = 55/96). Numeric SAFFRON results have not been released, with full data slated for a Presidential Symposium at the 2026 ESMO Congress, and the combination is already approved in China for the treatment of patients with EGFR-mutated nonsquamous NSCLC with MET amplification after EGFR TKI therapy. The combination also has temporary authorization for this indication in Switzerland.

NDA Submission Is Initiated for Zipalertinib Plus Chemotherapy in Frontline EGFR Exon 20 Insertion+ NSCLC

Submission of an NDA to the FDA has been initiated for zipalertinib (CLN-081/TAS6417) plus platinum-based chemotherapy for previously untreated, locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations, under the FDA’s Real-Time Oncology Review program, with anticipated completion of the submission by the end of 2026. In the phase 3 REZILIENT3 trial (NCT05973773), zipalertinib plus chemotherapy (n = 140) produced a median PFS of 14.5 months (95% CI, 12.9-21.4) by blinded independent central review vs 8.5 months (95% CI, 7.0-10.9) with chemotherapy alone (n = 139; HR, 0.50; 95% CI, 0.34-0.73; P = .00015). The respective ORRs were 65.0% vs 40.3% (P < .0001), and the respective median DORs were 14.2 vs 9.9 months. The PFS benefit with the zipalertinib-based combination was consistent across subgroups, including patients with brain metastases (HR, 0.38). The interim OS analysis at 30% event maturity showed an HR for death of 0.72 (95% CI, 0.42-1.23). Grade 3 or higher AEs occurred in 87.1% of patients receiving the combination vs 54.4% of those treated with chemotherapy alone, and these AEs were primarily hematologic (58.6% vs 28.7%). Grade 3 or higher EGFR-related toxicities were seen only with the combination, including rash (10.7%), stomatitis (5.0%), pneumonitis (2.1%), and diarrhea (1.4%). AEs led to zipalertinib discontinuation in 17.1% of patients, and treatment-related AEs resulting in death from sepsis or septic shock occurred in 3 patients (2.1%) in this arm. REZILIENT3 randomly assigned patients (n = 279) 1:1 after a safety lead-in to receive zipalertinib at 100 mg twice daily plus pemetrexed and carboplatin or cisplatin or to pemetrexed plus platinum chemotherapy alone, with optional crossover to receive zipalertinib at progression. The data were presented in a Presidential Symposium at the 2026 IASLC World Conference on Lung Cancer.