Zenocutuzumab Offers Durable Benefit After Progression in NRG1+ GI Tumors

Zenocutuzumab (Bizengri) continued to provide sustained clinical benefit and disease control in patients with advanced NRG1 fusion-positive (NRG1+) pancreatic adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) who continued therapy beyond progression, according to a post hoc analysis of the phase 1/2 eNRGy trial (NCT02912949).¹

The analysis assessed the efficacy and safety of zenocutuzumab in a subgroup of 17 patients with NRG1+ gastrointestinal tumors, including 12 patients with PDAC and 5 patients with CCA, who received at least 3 doses of therapy after progressive disease. The objective response rate (ORR) among this group was 35%, including 1 complete response, 5 partial responses, and 8 patients achieving stable disease.

Furthermore, the analysis reported a promising clinical benefit rate, with 65% of patients reported a complete or partial response or stable disease for at least 24 weeks. The safety analysis also revealed zenocutuzumab’s ongoing favorable tolerability profile, with no adverse event (AE)-related treatment discontinuation. These results were presented at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.

"These findings highlight an important therapeutic opportunity for patients with NRG1[+] pancreatic and biliary cancers, which are often difficult to treat," said Alison M. Schram, MD, Memorial Sloan Kettering Cancer Center and lead author, in a news release.¹ "In this analysis, zenocutuzumab provided ongoing benefit after radiographic progression, including multiyear disease control in some patients."

Zenocutuzumab in GI Cancers

Zenocutuzumab is an IgG1 bispecific antibody simultaneously targeting HER2 and HER3.² In December 2024, zenocutuzumab received accelerated approval from the FDA in advanced NRG1+ pancreatic cancer and non–small cell lung cancer after receiving priority review and fast track designation; it also held a breakthrough therapy designation in pancreatic cancer. It is specifically indicated for treatment of adults with unresectable or metastatic disease that has progressed on or after prior systemic therapy.

Most recently, the FDA granted the agent breakthrough therapy designation for advanced unresectable or metastatic NRG1+ CCA in October 2025. A supplemental biologics license application is expected to be filed to the FDA later this year seeking approval in this indication.

About the eNRGy Trial

The eNRGy trial is a multicenter, open-label, dose-escalation and -expansion trial designed to assess the safety, tolerability, immunogenicity, and antitumor activity of zenocutuzumab in patients with solid tumors harboring an NRG1 fusion.³ The trial’s primary end point is ORR; secondary end points include duration of response (DOR), clinical benefit rate, progression-free survival (PFS), and safety.

According to interim data presented last year at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, the ORR among 19 evaluable patients was 37%, with a median DOR of 7.4 months and clinical benefit rate of 58%.⁴ The PFS was reported at 9.2 months.

The safety profile was characterized by mostly grade 1 or 2 AEs, with no treatment-related discontinuations.

REFERENCES

1. Continued zenocutuzumab treatment beyond progression shows benefit in patients with NRG1+ pancreatic cancer and cholangiocarcinoma: New results from the eNRGy trial presented at ASCO GI. News release. Partner Therapeutics. January 9, 2026. Accessed January 20, 2026. https://tinyurl.com/5ypwksvw

2. Schram AM, Odintsov I, Espinosa-Cotton M, et al. Zenocutuzumab, a HER2xHER3 bispecific antibody, is effective therapy for tumors driven by NRG1 gene rearrangements. Cancer Discov. 2022;12(5):1233-1247. doi:10.1158/2159-8290.CD-21-1119

3. A study of zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion (eNRGy). ClinicalTrials.gov. Updated April 29, 2025. Accessed January 20, 2026. https://clinicaltrials.gov/study/NCT02912949

4. Zenocutuzumab-zbco granted FDA breakthrough therapy designation for NRG1+ cholangiocarcinoma; data highlighting potential of zenocutuzumab-zbco in NRG1+ cholangiocarcinoma to be presented at AACR-NCI-EORTC. News release. Partner Therapeutics. October 23, 2025. Accessed January 20, 2026. https://tinyurl.com/3yrjmdnu