The OncFive: Top Oncology Articles for the Week of 8/23

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 Daraxonrasib for Metastatic Pancreatic Ductal Adenocarcinoma

The FDA approved daraxonrasib (Rasonque), an oral RAS(ON) multiselective inhibitor, for adult patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who have received at least 1 prior systemic therapy or are not candidates for multi-agent systemic therapy, based on the phase 3 RASolute 302 trial (NCT06625320). In the RAS G12–mutated population, daraxonrasib produced a median overall survival (OS) of 13.2 months (95% CI, 10.0-not estimable [NE]) vs 6.6 months (95% CI, 5.4-8.2) with investigator’s choice chemotherapy (hazard ratio [HR], 0.40; 95% CI, 0.30-0.54; P = 5.9×10⁻¹⁰). Median progression-free survival (PFS) by blinded independent central review (BICR) was 7.3 months vs 3.5 months, respectively (HR, 0.45; 95% CI, 0.34-0.59), and the confirmed overall response rate (ORR) was 33.2% with daraxonrasib vs 11.8% with chemotherapy (P < .0001). Grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 43.6% of daraxonrasib-treated patients vs 57.5% with chemotherapy, and the most common any-grade TRAEs with daraxonrasib were rash (85%), diarrhea (58%), and stomatitis (53%). The approval, following presentation of the data at the 2026 ASCO Annual Meeting, was called one of the biggest breakthroughs in PDAC treatment history by Kim A. Reiss Binder, MD, in an interview with OncLive^®.

FDA Approves Zanidatamab-Based Regimens for First-Line HER2+ Locally Advanced or Metastatic Gastric Cancer

The FDA approved zanidatamab-hrii (Ziihera) plus fluoropyrimidine- and platinum-based chemotherapy, with or without tislelizumab-jsgr (Tevimbra), as first-line treatment for adults with HER2-positive, unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (GEA), based on the phase 3 HERIZON-GEA-01 trial (NCT05152147). In the primary analysis, the zanidatamab plus tislelizumab and chemotherapy triplet produced a median PFS of 12.4 months vs 8.1 months with trastuzumab (Herceptin) plus chemotherapy (HR, 0.63; 95% CI, 0.51-0.78; P < .0001), and median OS was 26.4 months vs 19.2 months, respectively (HR, 0.72; 95% CI, 0.57-0.90; P = .0043). At a median follow-up of 25.9 months, 18-month PFS rates were 43.9% with the triplet, 38.0% with the zanidatamab doublet, and 20.9% with trastuzumab-based therapy, and PD-L1 subgroup analyses from the 2026 ASCO Annual Meeting confirmed benefit regardless of PD-L1 expression. Safety was considered manageable with no new signals; diarrhea was the most common AE, with grade 3 or higher rates of 24.8% in the triplet arm, 20.0% in the doublet arm, and 12.9% in the control arm. The FDA also approved 2 companion diagnostics to identify HER2-positive GEA, and the application had previously received priority review in April 2026 under the Real-Time Oncology Review program.

FDA Grants Priority Review to Dostarlimab for dMMR/MSI-H Locally Advanced Rectal Cancer

The FDA granted priority review to a supplemental biologics license application for dostarlimab-gxly (Jemperli) for previously untreated, stage II/III mismatch repair–deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced rectal cancer, assigning a target action date of February 2027 under the Prescription Drug User Fee Act and granting eligibility for the National Priority Voucher program. The submission is supported by the phase 2 AZUR-1 trial (NCT05723562), which evaluated dostarlimab monotherapy in treatment-naive patients with dMMR/MSI-H locally advanced rectal cancer and met its primary end point of sustained clinical complete response (cCR) at 12 months. Full efficacy data are scheduled for presentation later in 2026; in an earlier phase 2 study (NCT04165772), all patients receiving dostarlimab monotherapy (n = 42) achieved a cCR, with 24 sustaining that response at 12 months over a median follow-up of 26.3 months. Safety in AZUR-1 was consistent with dostarlimab’s profile across solid tumors; in the earlier trial, common AEs included rash/dermatitis (21%), pruritus (13%), and fatigue (11%). Dostarlimab previously received FDA fast track and breakthrough therapy designations in this setting, and the AZUR-1 data support the potential for nonoperative management in select responders, sparing chemotherapy, radiation, and surgery.

sNDA Submitted to FDA for Gedatolisib in PIK3CA-Mutant, HR+/HER2-Negative Advanced Breast Cancer

A supplemental new drug application (sNDA) was submitted to the FDA for gedatolisib (Revtorpyk) plus fulvestrant (Faslodex), with or without palbociclib (Ibrance), for adults with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer harboring a PIK3CA mutation who progressed on or after at least 1 line of endocrine therapy, seeking to broaden gedatolisib’s July 2026 approval beyond PIK3CA wild-type disease. The filing is supported by the PIK3CA-mutant cohort (Study 2) of the phase 3 VIKTORIA-1 trial (NCT05501886), in which gedatolisib plus palbociclib and fulvestrant (the triplet) produced a median PFS of 11.1 months vs 5.6 months with alpelisib (Piqray) plus fulvestrant by BICR (HR, 0.50; 95% CI, 0.37-0.68; P < .0001). The gedatolisib doublet (fulvestrant without palbociclib) produced a median PFS of 11.3 months (HR vs control, 0.51; 95% CI, 0.33-0.79); ORR was 48.9% with the triplet and 35.7% with the doublet vs 26.0% with alpelisib plus fulvestrant, though OS data remained immature. TRAEs of any grade occurred in 98.0% of the triplet arm, 96.2% of the doublet arm, and 96.7% of the alpelisib arm, with lower rates of hyperglycemia and diarrhea in the gedatolisib arms than with alpelisib plus fulvestrant, though neutropenia was common with the triplet (any-grade, 63.4%). Gedatolisib is already FDA approved in combination with fulvestrant, with or without palbociclib, for hormone receptor–positive, HER2-negative advanced breast cancer without a PIK3CA mutation, based on the wild-type cohort of VIKTORIA-1, where the triplet and doublet significantly improved PFS vs fulvestrant alone.

TQB2440 Shows Equivalent tpCR to Reference Pertuzumab in Neoadjuvant HER2+ Early Breast Cancer

The pertuzumab (Perjeta) biosimilar TQB2440 demonstrated equivalent efficacy to reference pertuzumab, plus trastuzumab and docetaxel, as neoadjuvant therapy for estrogen receptor/progesterone receptor–negative, HER2-positive early or locally advanced breast cancer in a phase 3 equivalence trial (NCT05985187) published in ESMO Open. The independent review committee–assessed total pathological complete response (tpCR) rate was 58.9% with TQB2440 (n = 207) vs 58.1% with reference pertuzumab (n = 205), yielding a relative risk (RR) of 1.02 (90% CI, 0.89-1.16) that fell within the prespecified equivalence margins of 0.76-1.32. Secondary end points reinforced equivalence, with investigator-assessed tpCR of 60.4% vs 58.1% (RR, 1.04; 90% CI, 0.91-1.19) and objective response rates of 73.9% vs 67.3%, respectively, while median event-free survival and disease-free survival were not reached in either arm. Treatment-emergent adverse effects (TEAEs) occurred in 99.5% of patients receiving TQB2440 vs 100.0% with reference pertuzumab, with grade 3 or higher TEAEs in 79.7% vs 81.4%, respectively, and cardiotoxicity rates were comparable between arms (1.9% vs 1.5%). Pharmacokinetic and immunogenicity profiles were similar between agents, with anti-drug antibody positivity in 2.0% of TQB2440-treated patients vs 1.5% of those given reference pertuzumab, suggesting TQB2440 could offer a more cost-effective alternative in HER2-positive early breast cancer.

Honorable Mentions

• Teclistamab-cqyv (Tecvayli)–based induction regimens generated a minimal residual disease (MRD)–negative complete response (CR) rate of 91.8% (45/49) by the premaintenance timepoint in patients with transplant-eligible, newly diagnosed multiple myeloma, according to data from the phase 2 MajesTEC-5 trial (NCT05695508) published in Nature Medicine.
• The European Commission (EC) granted marketing authorization to sacituzumab govitecan-hziy (Trodelvy) in combination with pembrolizumab (Keytruda) for the treatment of adult patients with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic disease and whose tumors express PD-L1 with a combined positive score (CPS) of 10 or higher.
• The FDA granted fast track designation to ERAS-0015, an oral pan-RAS molecular glue, for the treatment of patients with metastatic pancreatic adenocarcinoma.
• The FDA granted fast track designation to SOT106, an investigational antibody-drug conjugate (ADC) which targets leucine-rich repeat-containing 15 (LRRC15), for the treatment of patients with soft tissue sarcoma (STS).