New Zenocutuzumab Findings Provide Hope for Targeting Rare NSCLC Subtypes

At the 2026 International Association for the Study of Lung Cancer (IASLC) Targeted Therapies of Lung Cancer (TTLC) Meeting, Zhaohui Liao Arter, MD, and colleagues presented updated findings from the ongoing phase 2 eNRGy trial (NCT02912949), which showed a benefit with continued zenocutuzumab-zbco (Bizengri) after radiographic progression among patients with NRG1 fusion-positive non–small cell lung cancer (NSCLC).^1,2 Of 27 evaluable patients, 8 continued treatment for more than 6 months beyond progression, which included 1 patient who kept receiving the agent for more than 23 months after progression.

Following the meeting, Arter, an assistant professor of Medicine in the Division of Hematology and Oncology and a thoracic oncologist at the University of California, Irvine School of Medicine, spoke with CancerNetwork® about the key implications of these data. According to Arter, these results highlight NRG1 fusions as targetable drivers in NSCLC care, show that progressive disease does not always indicate treatment failure, and affirm the safety profile of extended zenocutuzumab therapy, among other takeaways.

Transcript:

There are several key messages I would like colleagues to take away. First, NRG1 fusions are actionable targets. Even though they are rare—less than 1% [of patients]—they represent a clinically meaningful oncogenic driver that we should be looking for. If you are treating a patient with the driver in non–small cell lung cancer—especially invasive, mucinous adenocarcinoma—or KRAS wild-type pancreatic cancer, consider RNA-based next-generation sequencing to look for an NRG1 fusion.

Second, progressive disease does not always mean treatment failure. This analysis challenges the conventional paradigm, that RECIST-defined progression mandates stopping therapy. In select patients, such as in this case and this analysis, especially for those with oligoprogression, asymptomatic disease, and who maintained performance status, continuing zenocutuzumab can provide meaningful clinical benefit.

Third, the safety profile supports extended treatment, with no discontinuation due to adverse events, even in patients treated for over 3 years. We can feel confident offering prolonged therapy to patients who are benefiting.

Fourth, multidisciplinary care matters. The integration of local therapy, such as Gamma Knife, radiotherapy, and surgical resection with the continued systemic therapy requires tumor board discussion. This isn’t a one-size-fits-all approach. It does require individualized decision-making.

Finally, there’s a hope for [managing] rare molecular subtypes. For a long time, patients with NRG1 fusions had no targeted options. This work demonstrates that even for rare alterations, precision medicine can deliver meaningful clinical benefit. It is a reminder of why comprehensive genomic profiling matters and why we should continue investing in understanding and targeting real drivers.

References

1. Arter ZL, Schram AM, Rha SY, et al. Continued treatment beyond progression with zenocutuzumab, a HER2/HER3 bispecific antibody, in patients with NRG1+ NSCLC: analysis from the ongoing phase 2 eNRGy trial. Presented at the International Association for the Study of Lung Cancer (IASLC) 2026 Targeted Therapies of Lung Cancer Meeting; Huntington Beach, CA; February 20, 2026.
2. Zenocutuzumab treatment beyond progression demonstrates continued benefit in patients with NRG1+ non-small cell lung cancer: new results from the eNRGy trial. News release. Partner Therapeutics, Inc. February 20, 2026. Accessed March 3, 2026. https://tinyurl.com/3tzz5vma