The OncFive: Top Oncology Articles for the Week of 5/17

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 Datopotamab Deruxtecan for Unresectable or Metastatic TNBC

The FDA cleared datopotamab deruxtecan-dlnk (Datroway; Dato-DXd) for adult patients with unresectable or metastatic triple-negative breast cancer who are not candidates for PD-(L)1 inhibitor therapy, based on data from the phase 3 TROPION-Breast02 trial (NCT05374512). Dato-DXd significantly improved median overall survival (OS) vs investigator’s choice of chemotherapy, at 23.7 months and 18.7 months, respectively (HR, 0.79; 95% CI, 0.64-0.98; P = .0290). The antibody-drug conjugate also reduced the risk of disease progression or death by 43% per blinded independent central review (HR, 0.57; 95% CI, 0.47-0.69; P <.0001), with a median progression-free survival (PFS) of 10.8 months vs 5.6 months, respectively. The ORR was 64% with Dato-DXd vs 30% with chemotherapy. Serious adverse effects (AEs) occurred in 17% of patients (n = 319) treated with Dato-DXd, and included pneumonia, vomiting, COVID-19, and anemia. This approval came just 3 months after the agent received priority review designation in this indication in February 2026.

FDA Grants Sevabertinib Priority Review for First-Line HER2 TKD–Mutant NSCLC

The FDA has granted priority review to a new drug application for sevabertinib, for frontline use in adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring HER2 TKD–activating mutations, supported by findings from cohort F of the phase 1/2 SOHO-01 trial (NCT05099172). In 73 treatment-naive patients, sevabertinib induced an ORR of 71% (95% CI, 59%-81%), a disease control rate of 89% (95% CI, 80%-95%), and a median duration of response of 11.0 months (95% CI, 8.1-not estimable [NE]); the median PFS was not reached (95% CI, 9.6-NE). Best overall responses included a complete response in 4% and a partial response in 67% of patients. The most common treatment-related AEs comprised diarrhea (84%), rash (51%), and stomatitis (26%), with the majority being grade 1 to 2 (74%); grade 3 to 5 events were reported in approximately 23% of patients. Sevabertinib previously received FDA accelerated approval in November 2025 for pretreated HER2-mutant NSCLC based on findings from cohort D of SOHO-01; it is also under examination in the phase 3 SOHO-02 trial (NCT06452277) and phase 2 panSOHO trial (NCT06760819).

FDA Accepts sBLA for Nogapendekin Alfa Inbakicept in Papillary-Only BCG-Unresponsive NMIBC

The FDA has accepted for review a supplemental biologics license application seeking approval of nogapendekin alfa inbakicept-pmln (Anktiva) plus BCG for adult patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with papillary disease without carcinoma in situ (CIS). The Prescription Drug User Fee Act goal date is January 6, 2027; if approved, this would be the first FDA-approved bladder-sparing therapy specifically for papillary-only BCG-unresponsive NMIBC. The sBLA is supported by findings from cohort B of the phase 2/3 QUILT-3.032 trial (NCT03022825), in which 80 patients with high-grade papillary-only NMIBC experienced a 12-month disease-free survival rate of 58.2% (95% CI, 46.6%-68.2%), 36-month PFS rate of 83.1% (95% CI, 69.5%-91.0%), and 36-month cystectomy-free survival rate of 81.8% (95% CI, 68.1%-90.1%). The 36-month disease-specific survival (DSS) rate was 96.0% (95% CI, 88.2%-98.7%), with median DSS not yet reached. The regulatory agency noted that the scientific justification for extrapolating efficacy data from CIS to papillary-only disease will be the central focus of the review, acknowledging prior concerns about single-arm trial designs in papillary-only populations.

Suplexa Therapeutic Cells Receives FDA Fast Track Designation in MSI-H CRC

The FDA has granted fast track designation to suplexa, a non-engineered autologous cellular immunotherapy derived from a patient's own peripheral blood mononuclear cells, for the treatment of patients with microsatellite instability–high (MSI-H) colorectal cancer (CRC), supported by data from the phase 1 SUPLEXA-101 study (NCT05237206). Among 35 patients with solid tumors, suplexa achieved 12- and 24-week event-free survival rates of 61.2% (95% CI, 41.8%-75.1%) and 36.9% (95% CI, 19.3%-50.6%), respectively, with responses in the MSI-H CRC cohort extending beyond 80 weeks. No dose-limiting toxicities, treatment-related serious AEs, or injection-site reactions were reported, and treatment-emergent AEs were mild and self-limiting across a dose range of 3 to 20 doses of 2.5 billion cells per patient. Suplexa leverages the proprietary ENLIST platform to activate immune cells without genetic modification, enabling a highly scalable and reproducible manufacturing approach distinct from traditional engineered cell therapies. A phase 2 open-label trial evaluating suplexa in combination with checkpoint inhibitors vs checkpoint inhibitors alone in the first-line MSI-H CRC setting is planned based on these results.

CLN-049 Nets FDA Orphan Drug Designation for in R/R AML

The FDA has granted orphan drug designation to CLN-049 for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML), reflecting the urgent unmet need in this population, including those with TP53-mutated disease. CLN-049 is being examined in two early-phase studies: a 3-part, open-label, multicenter phase 1 trial (NCT05143996) in relapsed/refractory AML or myelodysplastic syndrome, and a phase 1 trial (EUCT2023-506572-27-00) in AML with minimal residual disease (MRD) at sites in Spain and Germany. Prior results from NCT05143996 indicated that patients treated at a target dose of at least 6 μg/kg (n = 23) achieved an ORR of 57% and a composite complete response (CRc) rate of 30%; at the 12 μg/kg dose level (n = 13), the ORR and CRc rates were 69% and 31%, respectively. CLN-049 previously received FDA fast track designation for relapsed/refractory AML in December 2025 based on these same phase 1 data.