The OncFive: Top Oncology Articles for the Week of 4/6

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 Nivolumab Plus Ipilimumab for dMMR/MSI-H Metastatic CRC

The FDA cleared nivolumab (Opdivo) paired with ipilimumab (Yervoy) for use in adult and pediatric patients aged 12 years or older with mismatch repair–deficient or microsatellite instability–high (MSI-H) unresectable or metastatic colorectal cancer based on data from the phase 3 CheckMate 8HW (NCT04008030). The doublet (n = 171) led to a median progression-free survival that was not yet reached (NR; 95% CI, 38.4-not evaluable [NE]) vs 5.8 months (95% CI, 4.4-7.8) with chemotherapy (n = 84), translating to a 79% reduction in the risk of disease progression or death (HR, 0.21; 95% CI, 0.14-0.32; P < .0001). “The combination of nivolumab plus ipilimumab is a very important step forward for better treatment for MSI-H mCRC,” Heinz-Josef Lenz, MD, of Keck School of Medicine of the University of the University of Southern California (USC), told OncLive. “There is no doubt that this is the most effective treatment we have for this MSI-H patient cohort without having significant increased toxicity.”

FDA Grants Traditional Approval to Larotrectinib for NTRK+ Solid Tumors

The regulatory agency awarded full approval to larotrectinib (Vitrakvi) for the treatment of adult and pediatric patients with solid tumors harboring an NTRK gene fusion without a known acquired resistance mutation; are metastatic or where surgical resection is likely to lead to severe morbidity; and have no satisfactory alternative options or that have progressed after treatment. The decision was based on findings from the following single-arm studies: the phase 1 LOXO-TRK-14001 (NCT02122913), phase 1/2 SCOUT (NCT02637687), and phase 2 NAVIGATE (NCT02576431) trials. Pooled data indicated that larotrectinib elicited an overall response rate of 60% (95% CI, 55%-65%) in these patients, with a median duration of response of 43.3 months (95% CI, 32.5-NE).

FDA Approves Nivolumab Plus Ipilimumab for Unresectable or Metastatic HCC

The nivolumab/ipilimumab combination won another approval for use as a frontline treatment in adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) based on data from the phase 3 CheckMate 9DW trial (NCT04039607), which showed that the dual immunotherapy (n = 335) led to a median overall survival (OS) of 23.7 months (95% CI, 18.8-29.4) vs 20.6 months (95% CI, 17.5-22.5) with investigator’s choice of single-agent sorafenib (Nexavar) or lenvatinib (Lenvima; HR, 0.79; 95% CI, 0.65-0.96; P = .018). “This is a very effective regimen, and I think it adds to additional options for patients with this disease,” Aiwu Ruth He, MD, PhD, of MedStar Georgetown University Hospital, told OncLive. “For sure, [this regimen] has its place in the frontline setting as a very potent regimen for advanced HCC [because of its] survival benefit, high response rate, rapid time to response, and prolonged disease control.”

Tarlatamab Yields OS Improvement in SCLC After Platinum Progression

The primary end point of the phase 3 DeLLphi-304 study (NCT05740566) was met when tarlatamab-dlle (Imdelltra) led to a statistically significant and clinically meaningful improvement in OS vs standard chemotherapy in patients with small cell lung cancer whose disease progressed on or following 1 line of platinum-based chemotherapy. The toxicity profile of the DLL3- and CD3-directed bispecific antibody proved to be consistent with prior reports. “We look forward to sharing these results with the scientific community and health authorities as we continue our efforts to bring [tarlatamab] to patients worldwide,” Jay Bradner, MD, of Amgen, stated in a news release.

Osimertinib Plus Dato-DXd Shows Efficacy in Post-Osimertinib EGFR-Mutated Advanced NSCLC

Findings from module 10 of the phase 2 ORCHARD study (NCT03944772) showed that when osimertinib (Tagrisso) plus datopotamab deruxtecan (Dato-DXd; Datroway) given at a dose of 4 or 6 mg/kg, it provided clinical benefits in patients with EGFR-mutated non–small cell lung cancer that had progressed on first-line osimertinib. When Dato-DXd was given at 4 mg/kg (n = 35), the ORR was 43% (80% CI, 31%-55%) with a median PFS of 9.5 months (95% CI, 7.2-9.8); when given at 6 mg/kg (n = 33), the combination led to an ORR of 36% (95% CI, 25%-49%) and a median PFS of 11.7 months (95% CI, 8.3-not calculable). “Encouraging outcomes were observed with osimertinib plus Dato-DXd in [this population], warranting further investigation of this combination in phase 3 studies,” Xiuning Le, MD, PhD, of The University of Texas MD Anderson Cancer Center, said in a presentation of the data during the 2025 European Lung Cancer Congress.