NRG1 fusion

It demonstrates that targeting these lesions can yield outcomes that meet or exceed the benchmarks set by the NAPOLI-1 trial (liposomal irinotecan plus 5-fluorouracil and leucovorin), with a median overall survival of 6.2 months and progression-free survival of 3.1 months. Objective response rates reach 33% with adagrasib in KRAS G12C PDAC, 22% with olaparib maintenance in germline BRCA1/2 cancers, and over 50% with RET or NTRK inhibitors with fusion alterations; pembrolizumab produces durable benefit in the 1-3% of tumours that are MSI-H/dMMR. Emerging data highlight NRG1 fusions (overall response rate 42% with zenocutuzumab), HER2 amplification, MTAP deletion with PRMT5 dependency and variant-specific (MRTX1133) or pan-RAS (daraxonrasib) inhibitors as the next frontier...Taken together, these advances represent a substantive therapeutic progress in PDAC over the past decades, even though they currently apply to a minority of patients. These findings underscore the necessity of comprehensive next-generation sequencing for every patient with advanced disease, enabling identification of rare, yet clinically meaningful, targets and moving PDAC management towards a precision-oncology paradigm.

These data support RRAS Q87L and RRAS2 Q72L as bona fide lung cancer drivers and nominate RRAS/RRAS2-mutant tumors as candidates for pan-RAS-targeted therapeutics. Our findings provide a biologic rationale and preclinical evidence to inform molecular testing paradigms and to prioritize enrollment of patients with RRAS/RRAS2-mutant NSCLC into future clinical trials of pan-RAS inhibitors.

This study confirms that NRG1 fusions are rare but significantly associated with lung cancer and the CD74 fusion partner. Our nationwide analysis represents the most comprehensive assessment of NRG1 fusions in Japanese patients with advanced solid tumors.

In this context, well-established negative predictive biomarkers, such as extended RAS extended mutations for anti-EGFR therapy in colorectal cancer, and positive predictive biomarkers, such as MSI status, BRAF p.V600E hotspot mutation, ERBB2 amplification, or even NTRK1, NTRK2, NTRK3, RET, and NRG1 fusions across gastrointestinal cancers, are mandatory to provide tailored clinical care, improve patient selection for treatment and clinical trials, maximize therapeutic benefit, and minimize unnecessary toxicity. In this review, we provide an updated overview of actionable genomic alterations in GI cancers and discuss their implications for clinical decision making.

We furthermore demonstrate the activity of sevabertinib in a cancer cell line dependent on a fusion of NRG1, a ligand for the HER2 family member and heterodimerization partner, HER3. Finally, we report patient responses to sevabertinib from a Phase 1/2 clinical trial, indicating potential benefit for patients with HER2-mutant lung cancer.

P2, N=13, Terminated, Merus N.V. | N=90 --> 13 | Trial completion date: Mar 2026 --> Jul 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2025 --> Jul 2025; Merus terminated the study early due to changes in organizational priorities.

In patients with resectable and borderline resectable pancreatic cancer, both neoadjuvant/perioperative mFOLFIRINOX and gemcitabine-nab-paclitaxel (GEM-Abraxane) have shown comparable median overall survival (~23-25 months) and R0 resection rates (~64-80%) in the SWOG S1505 trial...The efficacy of novel agents targeting specific molecular pathways, including CLDN18.2 and PDGFRα, is currently being evaluated in early-phase trials (e.g., CT041, IMAB362)...While pancreatic cancer remains a formidable adversary, recent advancements in therapeutic strategies offer hope for improving patient outcomes by leveraging cutting-edge technologies and fostering collaborative research endeavors. This literature review focuses on the latest clinical trial results of novel therapies that have emerged for the management of pancreatic cancer.

Although retrospective, these data support the hypothesis that NRG1 VUSes are frequently associated with poor prognosis and other oncogene alterations. In EGFR M+ patients treated with osimertinib, concurrent NRG1 alterations were an independent poor prognostic factor for both PFS and OS, raising the need of further validation.

Challenges and emerging opportunities are also discussed to guide future development. Overall, these findings strongly underscore the urgent need for continued investigation into the structural and functional mechanisms of NRG1 fusions and their clinical translation.

Its safety profile remains favorable, with most adverse effects being mild to moderate. This editorial explores the clinical potential of zenocutuzumab in reshaping treatment strategies for NSCLC and pancreatic adenocarcinoma.

P1/2, N=81, Active, not recruiting, Cancer Research UK | Recruiting --> Active, not recruiting

NRG1 fusion-related drugs can provide additional treatment options. Our study expands the NRG1 fusion gene landscape and provides a valuable reference for the comprehensive treatment of patients with NRG1 fusions.