Beyond Progression: Zenocutuzumab Offers New Hope for Lung Cancer

LEXINGTON, MA – February 20, 2026 – For patients with a rare and aggressive form of lung cancer, the fight often enters a daunting new phase when their initial treatment stops working. New findings presented today, however, suggest that for some, the best option may be to stay the course. A new analysis from the eNRGy clinical trial shows that the targeted therapy zenocutuzumab continues to provide meaningful, sometimes long-lasting, clinical benefit for patients with NRG1 fusion-positive non-small cell lung cancer (NSCLC) even after their disease shows signs of progression.

The results, unveiled at the 2026 International Association for the Study of Lung Cancer (IASLC) Targeted Therapies of Lung Cancer meeting, offer a beacon of hope and a potential shift in treatment strategy for a patient population with historically limited options.

A Breakthrough for a Difficult-to-Treat Cancer

Neuregulin 1 (NRG1) gene fusions are rare genetic alterations that act as powerful drivers of cancer growth. While found in only about 0.2% of all solid tumors, they are more common in certain lung cancers, like invasive mucinous adenocarcinoma. For years, patients diagnosed with NRG1+ NSCLC faced a grim prognosis, as standard treatments like chemotherapy and immunotherapy proved largely ineffective against this specific cancer subtype.

The landscape began to change in December 2024 with the U.S. Food and Drug Administration's accelerated approval of zenocutuzumab-zbco, marketed as BIZENGRI. Developed by Merus and commercialized in the U.S. by Partner Therapeutics, it became the first and only therapy specifically designed to target the NRG1 fusion pathway. The drug, a bispecific antibody, works by blocking the interaction between the HER2 and HER3 proteins, a critical signaling pathway that the NRG1 fusion hijacks to fuel tumor growth. Its approval was hailed by oncologists as a major milestone in precision medicine.

"Patients with advanced NRG1 fusion-positive non-small cell lung cancer often have limited treatment options after progression," said Dr. Misako Nagasaka of the University of California Irvine and senior author of the new analysis. The introduction of a targeted therapy like zenocutuzumab has already been transformative, and this new data explores how to maximize its benefit.

Sustained Benefit Beyond Initial Progression

The latest analysis focused on a critical question: What happens when a patient on zenocutuzumab shows signs of their cancer growing again? The standard clinical practice has often been to switch therapies at the first sign of radiographic progression. However, the data from Partner Therapeutics suggests a different path may be beneficial.

The post-hoc analysis included 27 patients with NRG1+ NSCLC from the eNRGy trial who continued taking zenocutuzumab for at least three more doses after their tumors progressed according to standard imaging criteria (RECIST). The results were striking. For these patients, the median total time on the drug increased to nearly 10 months, up from approximately 7 months before progression.

The benefit was not just a minor extension. Eight patients continued treatment for more than six months after their disease had technically progressed. One patient remained on zenocutuzumab for over 23 months post-progression and was still on the therapy as of December 2025. Another patient has been on the treatment for nearly four years in total, a remarkable duration for advanced lung cancer.

Crucially, this extended treatment came without a significant cost in terms of side effects. The therapy was reported to be generally well tolerated, and not a single patient in this group had to discontinue treatment due to adverse events.

Reshaping Clinical Strategy

These findings challenge the conventional "one-size-fits-all" approach to cancer progression and support a more nuanced clinical strategy. The analysis revealed that in 81% of these cases, patients experienced "oligoprogression," where only one or a few tumors began to grow while the rest of the cancer remained under control. This suggests the disease can progress heterogeneously, and the targeted therapy may still be effective against the majority of cancer cells.

In fact, 22% of the patients were able to continue on zenocutuzumab after receiving local treatments, such as radiotherapy, gamma knife surgery, or surgical resection, to manage the specific progressing lesions. This combination approach—tackling new growth locally while maintaining systemic control with the targeted drug—points toward a new paradigm in managing advanced cancer.

"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," stated Pritesh J. Gandhi, Chief Development Officer at Partner Therapeutics.

This approach is gaining traction among oncologists who specialize in lung cancer. The ability to continue a well-tolerated and effective drug, rather than switching to potentially more toxic and less effective alternatives, is a significant advantage. It also highlights the growing importance of comprehensive molecular testing, including both DNA and RNA sequencing, to identify the rare patients with NRG1 fusions who stand to benefit from this highly specific therapy in the first place.

Market Impact and Patient Hope

While BIZENGRI targets a niche patient population, its clinical success and the potential for extended treatment duration have significant commercial implications. The global market for NRG1 fusion-targeted therapies is projected to grow substantially, reaching over $240 million by 2035. For Partner Therapeutics, demonstrating that treatment can continue effectively for months or even years beyond initial progression directly increases the value proposition of the drug, enhancing revenue per patient and solidifying its position in a competitive oncology market.

For patients and advocacy groups, the news is a source of profound hope. Organizations like the LUNGevity Foundation have long championed the need for better testing to find rare driver mutations like NRG1. This new data provides a powerful argument not only for finding these patients but for rethinking how they are treated over the long term, offering the potential for more time and better quality of life.

BIZENGRI's journey is not yet complete. It was approved under the FDA's accelerated pathway based on tumor response rates and the duration of those responses. Continued approval is contingent upon verification of clinical benefit in confirmatory trials, and the ongoing eNRGy study will continue to provide crucial data. As with many powerful cancer therapies, BIZENGRI carries risks, including a boxed warning for potential harm to a fetus and warnings for infusion-related reactions, lung inflammation, and potential cardiac issues. Physicians and patients must carefully weigh these risks against the demonstrated benefits.

Still, the evidence for treating beyond progression marks a significant step forward, providing a new strategic tool for clinicians and a new horizon of possibility for patients battling this challenging disease. The company has indicated it will continue to work closely with physicians to gather more information on this promising approach, further refining the use of zenocutuzumab for those who need it most.