The OncFive: Top Oncology Articles for the Week of 2/22

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 Grants Accelerated Approval to Zongertinib for Unresectable or Metastatic, Nonsquamous NSCLC With HER2 TKD Mutations

The FDA granted accelerated approval to zongertinib (Hernexeos) for adult patients with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 TKD activating mutations. In the phase 1 Beamion LUNG-1 trial (NCT04886804), treatment-naive patients experienced an objective response rate (ORR) of 76%, with 6- and 12-month duration-of-response rates of 64% and 44%, respectively. The safety profile was consistent with expectations, with common adverse effects (AEs) including diarrhea, rash, fatigue, and nausea; serious AEs were reported in 36% of patients. A phase 3 trial, Beamion LUNG-2 (NCT06151574), is ongoing to compare zongertinib with standard-of-care therapy in the first-line advanced setting.

FDA Grants Full Approval to Encorafenib Plus Cetuximab/Chemotherapy for BRAF V600E+ mCRC

The FDA granted traditional approval to encorafenib (Braftovi) in combination with cetuximab (Erbitux) and fluorouracil-based chemotherapy for adults with metastatic colorectal cancer harboring BRAF V600E mutations. Data from the phase 3 BREAKWATER trial (NCT04607421) showed improved ORRs (61% vs 40%), progression-free survival (PFS; 12.8 vs 7.1 months), and overall survival (OS; 30.3 vs 15.1 months) compared with chemotherapy with or without bevacizumab (Avastin). Safety was consistent with known profiles of the agents, with common AEs including neuropathy, nausea, fatigue, rash, and diarrhea. This regulatory decision builds on prior accelerated approval for encorafenib plus cetuximab with mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin), offering a new first-line targeted combination for this aggressive molecular subset.

Iza-Bren Yields PFS and OS Benefits vs Chemo in Previously Treated, Advanced TNBC

Izalontamab brengitecan (iza-bren; BL-B01D1) met co-primary end points for PFS and OS in patients with previously treated, unresectable, or metastatic triple-negative breast cancer (TNBC) after taxane therapy in the phase 3 BL-B01D1-307 trial (NCT06382142). Iza-bren is an EGFR- and HER3-directed bispecific antibody-drug conjugate (ADC) that has received previous breakthrough designations in EGFR-mutated NSCLC and is under ongoing regulatory review in multiple solid tumors. Patients receiving iza-bren demonstrated clinically meaningful survival improvements vs physician’s choice chemotherapy, and safety was found to be manageable. These results highlight the potential of bispecific ADC technology to improve outcomes in difficult-to-treat cancers and expand therapeutic options for advanced TNBC.

Poll Results Shed Light on Top Bladder, Kidney Cancer Abstracts to Watch at the 2026 Genitourinary Cancers Symposium

At the 2026 Genitourinary Cancers Symposium (ASCO GU) in San Francisco, California, findings from key bladder and kidney cancer studies are being revealed. In bladder cancer, trials such as KEYNOTE-B15 (neoadjuvant/adjuvant enfortumab vedotin [Padcev] plus pembrolizumab [Keytruda]), IMvigor011 (NCT04660344; circulating tumor DNA–guided adjuvant atezolizumab [Tecentriq]), and NIAGARA (NCT03732677; perioperative durvalumab [Imfinzi]) are poised to advance biomarker-driven care, while RC48G001 (NCT04879329) explores HER2-directed therapy in advanced urothelial carcinoma. In kidney cancer, LITESPARK-022 (NCT05239728; adjuvant pembrolizumab plus belzutifan [Welireg]), LITESPARK-011 (NCT04586231; belzutifan plus lenvatinib [Lenvima] post–PD-(L)1 therapy), RAMPART (NCT03288532), and CYTOSHRINK (NCT04090710) trials are expected to refine adjuvant intensification and metastatic strategies. Polling across social media indicated strong clinician interest in the KEYNOTE-B15 and LITESPARK-022 studies.

CELMoDs May Represent Next Wave of Immunomodulation Approaches in Multiple Myeloma

CELMoDs, including iberdomide (CC-220) and mezigdomide (CC-92480), are poised to reshape multiple myeloma therapy by offering enhanced tumor cytotoxicity and immune stimulation vs traditional immunomodulatory drugs. Phase 1/2 trials, including CC-220-MM-001 (NCT02773030) and CC-92480-MM-002 (NCT03374085), showcased high response rates (up to 95% ORR in newly diagnosed patients with iberdomide-based therapy) and better minimal residual disease–negativity rates in those with relapsed/refractory disease. Ongoing phase 3 studies, including EXCALIBER-RRMM (NCT04975997), SUCCESSOR-1 (NCT05519085), SUCCESSOR-2 (NCT05552976), MagnetisMM-302 (NCT06215118), and MELT-MM3 (NCT06645678), are examining these agents across lines of therapy and in combination with daratumumab (Darzalex), bispecific antibodies, or proteasome inhibitors. CELMoDs may complement CAR T-cell and bispecific therapies, enabling deeper, durable responses and potentially long-term treatment holidays.