The OncFive: Top Oncology Articles for the Week of 10/4/2026

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 Atezolizumab Plus Chemo for Stage III dMMR Colon Cancer

The FDA has approved atezolizumab (Tecentriq) plus a fluoropyrimidine and oxaliplatin for the adjuvant treatment of adult and pediatric patients 2 years of age and older with stage III mismatch repair–deficient (dMMR) colon cancer, along with subcutaneous atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) plus chemotherapy for patients 12 years of age and older who weigh at least 40 kg. The approval was supported by data from the phase 3 ATOMIC/ML39057 trial (NCT02912559), in which atezolizumab plus modified FOLFOX6 (mFOLFOX6; oxaliplatin, leucovorin, and fluorouracil) improved disease-free survival (DFS) vs mFOLFOX6 alone (HR, 0.50; 95% CI, 0.35-0.73; P = .0001), with the median DFS not reached [NR] in either arm. At a median follow-up of 40.9 months (interquartile range [IQR], 26.7-58.6), the 3-year DFS rate was 86.3% (95% CI, 81.8%-89.8%) with atezolizumab vs 76.2% (95% CI, 70.9%-80.6%) with mFOLFOX6 alone, whereas the median overall survival (OS) values were similar between the arms at a median follow-up of 45.8 months (IQR, 32.0-64.7). The 5-year OS rates were 89.7% (95% CI, 85.2%-92.9%) vs 87.9% (95% CI, 83.1%-91.4%), respectively (stratified HR, 0.90; 95% CI, 0.55-1.47; P = .68). Any-grade adverse effects (AEs) occurred in all patients receiving atezolizumab plus mFOLFOX6 (n = 346) vs 98.5% of those receiving chemotherapy alone (n = 334), with grade 3/4 AEs occurring in 84.1% vs 71.9% of patients, respectively. Grade 5 AEs occurred in 6 patients in the atezolizumab arm vs 2 patients in the control arm, including 2 treatment-related deaths (sudden death and sepsis). ATOMIC randomly assigned patients with completely resected stage III dMMR colon adenocarcinoma, including those with Lynch syndrome, 1:1 to receive 12 cycles of mFOLFOX6 with or without atezolizumab at 840 mg every 2 weeks for 12 cycles followed by 13 cycles of atezolizumab monotherapy, with DFS as the primary end point and OS and safety as secondary end points.

FDA Approves Tucatinib Plus Trastuzumab/Pertuzumab as First-Line Maintenance in Advanced HER2+ Breast Cancer

The FDA has approved tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and pertuzumab (Perjeta) for the maintenance treatment of adult patients with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment. In the randomized, double-blind phase 3 HER2CLIMB-05 trial (NCT05132582), tucatinib plus trastuzumab and pertuzumab reduced the risk of disease progression or death by 35.9% vs placebo plus trastuzumab and pertuzumab (HR, 0.64; 95% CI, 0.51-0.80; 2-sided P < .0001), with a median investigator-assessed progression-free survival (PFS) of 24.9 months (95% CI, 21.3-NR) vs 16.3 months (95% CI, 12.6-18.7). The OS data were immature at the time of the PFS analysis. Eligible patients had no disease progression after 4 to 8 cycles of trastuzumab, pertuzumab, and a taxane before being randomly assigned 1:1 to receive tucatinib at 300 mg twice daily or placebo, each with trastuzumab and pertuzumab every 3 weeks. Investigator-assessed PFS per RECIST 1.1 criteria served as the primary end point. Grade 3 or higher treatment-emergent AEs (TEAEs) occurred in 42.3% of patients in the tucatinib arm (n = 326) vs 24.4% of those in the control arm (n = 324), most commonly elevated alanine aminotransferase levels (13.5% vs 0.6%), elevated aspartate aminotransferase levels (7.1% vs 0.6%), and diarrhea (6.1% vs 4.0%). TEAEs led to treatment discontinuation in 13.8% vs 4.6% of patients, respectively.

Iberdomide Plus Daratumumab/Dexamethasone Yields Significant PFS Benefit in R/R Myeloma

Iberdomide (Zenbexus) plus subcutaneous daratumumab and hyaluronidase-fihj (Darzalex Faspro) and dexamethasone (IberDd) led to a statistically significant PFS improvement vs daratumumab, bortezomib (Velcade), and dexamethasone (DVd) in relapsed/refractory multiple myeloma, meeting the PFS dual primary end point of the phase 3 EXCALIBER-RRMM trial (NCT04975997). At a median follow-up of 23 months, the median PFS was 42 months with IberDd vs 20 months with DVd (HR, 0.49; P < .000001), translating to a 51% reduction in the risk of progression or death, with full PFS data to be presented at the 2026 ASH Annual Meeting in December. The trial’s other dual primary end point, minimal residual disease (MRD)–negative complete response (CR) rate, was previously reported in The Lancet Oncology: at a median follow-up of 15.7 months (IQR, 12.8-23.2), the MRD-negative CR rate was 41.1% with IberDd vs 21% with DVd (difference, 20.1%; 95% CI, 11.5%-28.6%; P < .0001; odds ratio, 2.75; 95% CI, 1.77-4.30), supporting the FDA’s August 2026 accelerated approval of the regimen. In that analysis, grade 3/4 TEAEs occurred in 91.7% of patients receiving IberDd vs 70.1% of those receiving DVd, including neutropenia (84.3% vs 11.3%), thrombocytopenia (12.7% vs 44.1%), and infections (35.8% vs 21.1%). TEAEs led to treatment discontinuation in 8.7% vs 3.3% of patients, respectively. EXCALIBER-RRMM enrolled 939 patients who had received 1 to 2 prior lines of therapy. Stage 1 of the trial (n = 279) selected the 1.0-mg iberdomide dose, and stage 2 (n = 660) randomly assigned patients 1:1 to receive IberDd or DVd. OS, sustained MRD negativity rate, and overall response rate (ORR) are among the secondary end points.

VIR-5500 Receives FDA Fast Track Designation in mCRPC

The FDA has granted fast track designation to VIR-5500 (AMX-500), an investigational prostate-specific membrane antigen (PSMA)–targeted, dual-masked T-cell engager, for the treatment of patients with late-line metastatic castration-resistant prostate cancer (mCRPC). In evaluable patients treated at a dose of at least 3000 µg/kg in the phase 1 trial (NCT05997615; n = 17), decreases in prostate-specific antigen (PSA) of at least 50% occurred in 82% of patients, and decreases of at least 90% were reported in 45% of patients. Among those evaluable per RECIST 1.1 criteria (n = 11), the ORR was 45%, with 4 of the 5 responses confirmed. In the dose-escalation portion (n = 58), no dose-limiting toxicities (DLTs) were reported, and grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 12% of evaluable patients. Cytokine release syndrome occurred in 50% of patients and was generally grade 1. VIR-5500 binds PSMA on tumor cells and CD3 on T cells through the PRO-XTEN masking platform, which keeps the molecule inactive until tumor-associated proteases cleave the masks within the tumor microenvironment. The ongoing first-in-human, open-label, nonrandomized phase 1 study includes 6 dose-expansion cohorts that began dosing in April 2026, evaluating monotherapy in taxane-naive, radioligand therapy–naive, and radioligand therapy–exposed mCRPC and combinations with enzalutamide (Xtandi) or docetaxel (Taxotere) in early-line mCRPC and with darolutamide (Nubeqa) in metastatic hormone-sensitive prostate cancer, with DLTs and TRAEs as primary end points in dose escalation and PSA response rate and ORR as primary efficacy end points in dose expansion.

Epcoritamab Plus R-CHOP Meets PFS End Point in Newly Diagnosed DLBCL

Epcoritamab-bysp (Epkinly) plus R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) produced a statistically significant and clinically meaningful PFS improvement vs R-CHOP alone in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) score of 3 to 5, meeting the primary end point of the phase 3 EPCORE DLBCL-2 trial (NCT05578976). In the primary population of patients with an IPI score of 3 to 5, epcoritamab plus R-CHOP reduced the risk of progression or death by 51% (HR, 0.49; 95% CI, 0.35-0.69; P < .0001), and a 51% reduction in this risk was also seen in the overall IPI 2 to 5 population, a key secondary end point (HR, 0.49; 95% CI, 0.36-0.67; P < .0001). The safety profile of epcoritamab plus R-CHOP was generally well tolerated and consistent with the safety profiles of each agent alone. The global, open-label, randomized trial enrolled patients 18 to 79 years with newly diagnosed CD20-positive DLBCL and an IPI score of 2 to 5 (with IPI 2 capped at approximately 30% of enrollment), randomly assigning them 2:1 to receive epcoritamab plus R-CHOP for 6 cycles followed by 2 cycles of epcoritamab monotherapy or R-CHOP for 6 cycles followed by 2 cycles of rituximab monotherapy, in 21-day cycles. The primary end point was PFS per Lugano 2014 criteria by independent review committee in patients with an IPI score of 3 to 5, with overall-population PFS as the key secondary end point and event-free survival, complete remission rate, OS, and MRD negativity rate among other secondary end points. The data will be submitted for presentation at a future medical meeting and shared with global health authorities.