The Targeted Pulse: Trial Breakthroughs and FDA Decisions

Welcome to the first edition of The Targeted Pulse of 2026, your weekly wrap-up of the top developments in oncology. This week, we saw FDA breakthroughs, learned about care-changing trial data, and heard from expert clinicians in the field. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.

Tafasitamab Plus R-CHOP Improves PFS in First-Line DLBCL: Phase 3 Results

The phase 3 frontMIND trial demonstrated that adding tafasitamab (Monjuvi), a CD19-targeted monoclonal antibody, and lenalidomide (Revlimid) to frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) significantly improves outcomes for patients with newly diagnosed, high-intermediate, or high-risk diffuse large B-cell lymphoma (DLBCL).

In the study of 900 patients, the experimental quadruplet met its primary end point, showing a statistically significant improvement in progression-free survival (PFS) compared to R-CHOP alone (HR, 0.75; 95% CI, 0.59–0.96; P =.019). The regimen also met the key secondary end point of investigator-assessed event-free survival. Safety was consistent with the known profiles of the individual agents, with no new safety signals observed. These results suggest a potential shift in the first-line treatment standard for aggressive DLBCL.

FDA Grants Breakthrough Status to Sevabertinib in 1L HER2+ NSCLC

The FDA has granted breakthrough therapy designation (BTD) to sevabertinib (Hyrnuo, formerly BAY 2927088) for the first-line treatment of unresectable or metastatic non–small cell lung cancer harboring activating HER2 (ERBB2) mutations. This oral, highly selective tyrosine kinase inhibitor (TKI) targets both HER2 and EGFR mutations, specifically HER2 exon 20 insertions.

Clinical foundation for this BTD stems from the SOHO-01 study. In treatment-naive patients, sevabertinib demonstrated an investigator-assessed overall response rate (ORR) of 59.0% and a disease control rate of 84.6%. The safety profile remains favorable, notably lacking reports of interstitial lung disease, though diarrhea is a common adverse event (AE). An ongoing phase 3 trial, SOHO-02, is currently comparing sevabertinib against standard platinum-based chemotherapy plus pembrolizumab (Keytruda) in the frontline setting.

Real-World Tolerability and Safety Results for Axatilimab in cGVHD

Updated results from an expanded access program and the phase 2 AGAVE-201 trialconfirm the long-term safety and tolerability of axatilimab (Niktimvo), a first-in-class CSF-1R monoclonal antibody, for patients with heavily pretreated chronic graft-versus-host disease. Targeting the macrophage-monocyte axis to address inflammation and fibrosis, the approved 0.3 mg/kg biweekly dose maintained a manageable safety profile over a median follow-up of 34 months.

Long-term data showed a 46-month overall survival (OS) rate of 77.6% in the 0.3 mg/kg cohort. While serious treatment-emergent AEs occurred in 53.3% of this group—primarily pneumonia and respiratory infections—incidences generally decreased with prolonged exposure. Common AEs included fatigue and transient laboratory enzyme elevations (AST, CPK, lipase). These findings support axatilimab as a durable, low-toxicity option for patients failing multiple prior lines of therapy.

Ribociclib Plus Letrozole Yields Meaningful Responses in Ovarian Cancer

Updated results from the phase 2 GOG 3026 trial demonstrate that combining ribociclib (Kisqali), a CDK4/6 inhibitor, with letrozole provides significant activity in patients with recurrent low-grade serous ovarian cancer (LGSOC). In this often chemoresistant, hormonally driven malignancy, the combination achieved a confirmed ORR of 30.6% and a clinical benefit rate of 84%.

The regimen showed notable durability, with a median duration of response of 21.2 months and a median PFS of 14.5 months. Median OS reached 44.5 months. Safety was consistent with the known CDK4/6 inhibitor profile; the most common grade ≥3 AE was neutropenia (47%), which was manageable via dose modifications. These findings establish the ribociclib/letrozole doublet as a meaningful therapeutic option for recurrent LGSOC.

FDA and EMA Grant Orphan Drug Status to Novel Imaging Drug for Pancreatic Cancer

The FDA and European Medicines Agency have granted orphan drug designationto CPI-008 (cRGD-ZW800-1), a novel, integrin-targeted, zwitterionic imaging agent, for the intraoperative margin detection of pancreatic cancer. By binding to integrins overexpressed on tumor cells and vascular endothelium, CPI-008 employs near-infrared fluorescence to enhance real-time tumor visualization.

This designation is supported by the phase 2 FLUOPANC trial, which demonstrated the agent's feasibility and safety in 20 patients. Administered as a single intravenous bolus 2 to 24 hours pre-surgery, CPI-008 showed strong imaging capabilities, quantified by tumor-to-background ratios in vivo and ex vivo. These findings suggest CPI-008 may optimize surgical precision and radicality in treating pancreatic ductal adenocarcinoma and extrahepatic cholangiocarcinomas.