Exposure to zenocutuzumab-zbco (Bizengri) past the point of radiographic progression afforded clinical benefit without sacrificing tolerability in patients with advanced NRG1 fusion–positive non–small cell lung cancer (NSCLC), according to data from a post hoc analysis of the phase 2 eNRGy trial (NCT02912949) presented at the International Association for the Study of Lung Cancer 2026 Targeted Therapies of Lung Cancer Meeting.1
Findings showed that 8 of the 27 patients who received at least 3 doses of zenocutuzumab after disease progression continued therapy for at least 6 months past that point. One patient remained on treatment for more than 23 months; treatment for this patient was ongoing as of December 2025. Another patient had been on therapy for approximately 4 years overall.
The median time on treatment increased to approximately 10 months with zenocutuzumab, compared with 7 months prior to progression. Oligoprogression occurred in 81% of patients, and diffuse progression was documented in 19%. Local intervention was required for progressing lesions, including radiotherapy, gamma knife surgery, and surgical resection, and 22% of patients were able to continue zenocutuzumab afterward.
No patients discontinued treatment because of an adverse effect, and investigators deemed the safety profile of the agent to be well tolerated.
“Patients with advanced NRG1 fusion–positive NSCLC often have limited treatment options after progression,” Misako Nagasaka, MD, PhD, associate clinical professor in the Division of Hematology and Oncology, Medicine, at the University of California, Irvine, School of Medicine, and senior study author, stated in the news release. “In this analysis, continued zenocutuzumab treatment beyond RECIST progression provided meaningful, sometimes long-lasting, clinical benefit while maintaining a favorable tolerability profile.”
Zenocutuzumab Beyond Progression: Key Insights From the eNRGy Analysis
- Eight patients who continued zenocutuzumab after radiographic progression remained on treatment for at least 6 months.
- Most patients experienced oligoprogression, which was often managed with local interventions such as radiotherapy or surgery, allowing some to remain on treatment.
- No treatment discontinuations due to adverse effects were reported, suggesting that zenocutuzumab can be safely continued beyond progression in select patients.
What indications does zenocutuzumab currently hold?
The FDA previously approved the use of zenocutuzumab for patients with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring an NRG1 gene fusion who have received prior treatment.2
The agent’s efficacy and safety were evaluated in the global, multicenter, open-label eNRGy trial, which enrolled patients 18 years or older with locally advanced unresectable or metastatic solid tumors harboring an NRG1 gene fusion who had previously received or were unable to receive standard therapy.3 An ECOG performance status of 0 to 2, at least 1 measurable lesion according to RECIST 1.1 or evaluable disease for select patients, and an estimated life expectancy of at least 12 weeks was also required.
Patients with known symptomatic or unstable brain metastases, leptomeningeal metastases, HIV, active hepatitis B with no history of antiviral treatment, or hepatitis C were excluded from enrollment.
All patients received zenocutuzumab at 750 mg once every 2 weeks until disease progression.
The primary end points of the study were investigator-assessed objective response rate (ORR) per RECIST 1.1 criteria and duration of response (DOR). Secondary end points included ORR per blinded independent central review, clinical benefit rate, DOR, time to response, and safety.
Pivotal efficacy findings from the study showed an ORR of 33% (95% CI, 22%-46%) with zenocutuzumab in evaluable patients with NSCLC (n = 64). The median DOR was 7.4 months (95% CI, 4.0-16.6).
What is the significance of these post hoc findings?
“These data underscore the potential heterogeneity of disease at progression and provide evidence that continued use of a targeted therapy, like zenocutuzumab, may offer meaningful clinical benefit without introducing new safety concerns,” Pritesh J. Gandhi, chief development officer at Partner Therapeutics, stated in the news release. “We continue to work with physicians to generate more information on the use of zenocutuzumab beyond progression.”
References
- 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 8, 2026. https://www.partnertx.com/zenocutuzumab-treatment-beyond-progression-demonstrates-continued-benefit-in-patients-with-nrg1-non-small-cell-lung-cancer-new-results-from-the-enrgy-trial/
- FDA grants accelerated approval to zenocutuzumab-zbco for non-small cell lung cancer and pancreatic adenocarcinoma. FDA. December 4, 2024. Accessed March 8, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zenocutuzumab-zbco-non-small-cell-lung-cancer-and-pancreatic
- A study of zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion (eNRGy). ClinicalTrials.gov. Updated April 29, 2025. Accessed March 8, 2026. https://clinicaltrials.gov/study/NCT02912949?term=NCT02912949&rank=1
