A bile-duct cancer with a rare gene fusion gets its first targeted drug

The Food and Drug Administration added cholangiocarcinoma — cancer of the bile ducts — to the label of Bizengri (zenocutuzumab) on 8 May, for adults whose tumours carry a neuregulin 1 (NRG1) gene fusion and whose disease has progressed after prior treatment [s1][s2]. The evidence base is unusually small: 19 patients, of whom 36.8% had their tumours shrink, because an NRG1 fusion in bile-duct cancer is one of the rarest targetable events in oncology [s2].

Zenocutuzumab, a bispecific antibody from Merus marketed in the US by Partner Therapeutics, works by binding both HER2 and HER3 and blocking the signal an NRG1 fusion sends through them to drive tumour growth [s3]. The drug first reached the market in 2024 for NRG1-fusion lung and pancreatic cancers; the cholangiocarcinoma indication extends the same biomarker logic to a third tumour type [s2].

A driver defined by its rarity

NRG1 fusions are recurrent cancer drivers, but they turn up in only a small percentage of solid tumours, and cholangiocarcinoma is itself an uncommon cancer [s3]. The result is a target so scarce that the registrational programme could not run as a conventional trial in one disease. Instead, the pivotal study — eNRGy — enrolled 204 patients across 12 different tumour types who shared the same fusion, and treated them all with the same antibody at 750 mg intravenously every two weeks [s3].

In the New England Journal of Medicine report of that basket study, 30% of 158 evaluable patients responded (95% confidence interval, 23 to 37), with responses lasting a median of 11.1 months [s3]. The signal was strongest in the two most common fusion-bearing cancers: 29% of 93 patients with non-small-cell lung cancer and 42% of 36 with pancreatic cancer [s3]. Overall progression-free survival was 6.8 months [s3]. These are the numbers that established the drug's activity; the case for using it in bile-duct cancer rests on showing the same target behaves the same way there.

Nineteen patients

The cholangiocarcinoma cohort that supported the new indication numbered 19 [s2]. Their confirmed overall response rate, judged by blinded independent review, was 36.8% (95% confidence interval, 16.3 to 61.6) — one complete response and five partial responses [s2]. Responses lasted between 2.8 and 12.9 months, and 28.6% of responders held their response for at least six months [s2]. All 16 patients with a reported site of origin had intrahepatic cholangiocarcinoma, and most had already been through cisplatin-and-gemcitabine chemotherapy, the standard first-line regimen [s2].

The wide confidence interval — a response rate that could plausibly be anywhere from roughly one in six to three in five — is the direct consequence of a 19-patient sample [s2]. That is not a flaw in the analysis so much as the reality of a mutation this rare: there is no larger dataset to be had, and a randomised comparison in NRG1-fusion cholangiocarcinoma is not a realistic prospect. The fusions themselves were varied, pairing NRG1 with a scatter of different partner genes across the 19 tumours, which is part of why these cancers are easy to miss unless a laboratory is looking for the fusion specifically [s2]. The label also carries a boxed warning for embryo-fetal toxicity, with advice on contraception during treatment [s2].

Notably, the label lists the cholangiocarcinoma indication without the "accelerated approval" qualifier that accompanies the drug's lung and pancreatic indications, both of which remain contingent on confirmatory trials [s2].

What it means for testing

The approval is only useful to a patient whose tumour has actually been tested for an NRG1 fusion, and these fusions are best detected by RNA-based sequencing, which not every pathology lab runs by default [s2]. The lesson is the one that recurs across biomarker-driven cancer drugs, from HER2-mutant lung cancer onward: the medicine is worth nothing to a patient whose driver was never looked for. For the small number of people with NRG1-fusion bile-duct cancer — a disease that has also drawn attention as an occupational cancer — a targeted option now exists where there was none, on the strength of 19 cases.

Sources

• [s1] U.S. Food and Drug Administration. BLA 761352/S-010 Supplement Approval Letter — Bizengri (zenocutuzumab-zbco) injection. 8 May 2026.
• [s2] U.S. Food and Drug Administration. Bizengri (zenocutuzumab-zbco) injection — Prescribing Information. 8 May 2026.
• [s3] Schram AM, Goto K, Kim DW, et al. Efficacy of Zenocutuzumab in NRG1 Fusion-Positive Cancer. New England Journal of Medicine. 5 February 2025.