The OncFive: Top Oncology Articles for the Week of 7/27

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 Issues CRL for Odronextamab in Relapsed/Refractory Follicular Lymphoma

The FDA issued a second complete response letter (CRL) for the biologics license application (BLA) seeking approval of odronextamab (Ordspono) for use in adults with relapsed/refractory follicular lymphoma (FL) after 2 or more prior lines of therapy, citing manufacturing site inspection issues. The letter was unrelated to safety or efficacy, and follows a prior CRL from March 2024 that focused on confirmatory trial enrollment. The BLA was backed by results from the ELM-2 (NCT03888105) and ELM-1 (NCT02290951) trials, which showed high overall response and complete response (CR) rates in heavily pretreated patients. In ELM-2, the median time to first CR was 2.6 months, with a median duration of response of 15.8 months. A phase 3 confirmatory trial, OLYMPIA-1, is ongoing, and the agent is already approved in the European Union for relapsed/refractory FL and diffuse large B-cell lymphoma.

FDA Grants Priority Review to Perioperative Durvalumab in Resectable Gastric/GEJ Cancer

The regulatory agency has granted priority review to a supplemental BLA seeking approval of durvalumab (Imfinzi) for use in patients with resectable, early-stage, locally advanced gastric and gastroesophageal junction (GEJ) cancers, with a decision expected in Q4 2025. The application is based on data from the phase 3 MATTERHORN trial (NCT04592913), where perioperative durvalumab plus FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) chemotherapy significantly reduced the risk of disease progression, recurrence, or death by 29% vs FLOT alone. At the time of interim analysis, median event-free survival was not reached in the durvalumab arm vs 32.8 months in the control arm. The pathologic CR rate was also notably higher with durvalumab (19.2% vs 7.2%); 2-year OS rates favored the immunotherapy arm (75.7% vs 70.4%). The safety profile of the combination was consistent with known toxicities and did not lead to increased delays in surgery or adjuvant treatment.

Acalabrutinib/Venetoclax sNDA Under FDA Review for Previously Untreated CLL

A supplemental new drug application has been submitted to the FDA for the fixed-duration, all-oral combination of venetoclax (Venclexta) and acalabrutinib (Calquence) for frontline use in patients with chronic lymphocytic leukemia (CLL). The submission is based on phase 3 AMPLIFY trial (NCT03836261) data, which showed the regimen significantly improved progression-free survival (PFS) vs standard chemoimmunotherapy. At a median follow-up of nearly 41 months, the 36-month PFS rate was 76.5% for acalabrutinib plus venetoclax vs 66.5% for chemoimmunotherapy. The regimen also demonstrated a manageable safety profile, with low rates of tumor lysis syndrome (0.3%) and fewer grade 3 or higher adverse effects (AEs) vs chemoimmunotherapy. If approved, the combination would represent the first fixed-duration oral-only regimen in the frontline CLL setting, potentially changing the standard of care.

Gedatolisib-Based Regimens Prolong PFS in HR+/HER2–, PIK3CA Wild-Type Advanced Breast Cancer

Gedatolisib, a pan‑PI3K/mTOR inhibitor, demonstrated significant improvements in PFS when combined with palbociclib (Ibrance) and fulvestrant (Faslodex) or fulvestrant alone in PIK3CA wild-type hormone receptor–positive/HER2-negative advanced breast cancer, according to topline data from the phase 3 VIKTORIA‑1 trial (NCT05501886). The triplet regimen reduced the risk of progression or death by 76% vs fulvestrant alone (HR, 0.24; P < .0001), with a median PFS of 9.3 months vs 2.0 months, respectively. The doublet also showed a 67% reduction in risk (HR, 0.33), with a median PFS of 7.4 months. Treatment discontinuations and rates of hyperglycemia and stomatitis were lower than previously reported with other regimens. A new drug application is planned for submission to the FDA in Q4 2025, with full trial results expected at an upcoming 2025 medical meeting.

FDA Grants Fast Track Designation to Ateganosine for NSCLC

The regulatory agency has granted fast track designation to ateganosine (THIO), a first-in-class telomere-targeting agent, for the treatment of advanced non–small cell lung cancer (NSCLC). Ateganosine is currently under investigation in the phase 2 THIO-101 trial (NCT05208944) in combination with cemiplimab (Libtayo) for patients who progressed on previous immune checkpoint inhibitor–based therapies. The trial includes multiple dosing cohorts and is evaluating response rates, disease control, and safety, with a goal of accelerating regulatory timelines. MAIA Biotechnology, the drug developer, noted that ateganosine has shown superior preclinical efficacy and overall survival vs currently approved options in this setting. A potential FDA decision could come as early as 2026 if development continues as planned.