ASCO 2026 | HERBOT: 1L trastuzumab, nivolumab, gemcitabine & cisplatin in HER2+ BTC

The biliary tract cancer is a very deadly disease. So even the current standard of care, which is anti-PD-1, anti-PD-L1, combined with the Gemcitabine plus cisplatin, the response rate is below 30%. And the progression-free survival is about seven months, and the overall survival rate is only slightly exceeding one year. So the HER2 overexpression or amplification is identified in about 15% of the biliary cancer patients and is known to be related to the worst prognosis. It has become a very exciting therapy target since there were many second-line trials. But the HER2-targeted strategies have never been evaluated in the first-line setting. So that’s why I designed the HERBOT trial. The HERBOT trial is the multi-institutional single-arm investor-initiated phase 1b/2 trial. The eligible patients include the HER2-positive biliary tract cancer, metastatic locally advanced unresectable patients, which include gallbladder cancer, intrahepatic or extrahepatic cholangiocarcinoma. The HER2-positive was centrally confirmed by the HER2-IHC 3-positive, while 2-positive is FISH-positive. The patient received Trastuzumab plus Nivolumab every three weeks, plus Gemcitabine plus cisplatin. And the Gemcitabine plus cisplatin was continued until cycle 9, followed by the Trastuzumab plus Nivolumab maintenance every three weeks. The primary endpoint was the recommended phase 2 dose for the phase 1B part, and investigator-assessed confirmed objective response rate for part 2, a phase 2 part. So about a total of 40 patients were enrolled and analyzed. Most of the patients had an equal performance status 1, and about 70% of patients had the gallbladder cancer, and two-thirds of the patients had the HER2 IHC3 positive. The study method is primary endpoint with the objective response rate of 55% and the disease control rate of 95%. Response was durable with the duration of response of 12.6 months. After the 17 months of the follow-up, the median PFS was 10.6 months and the overall survival was not reached at the time of analysis. In terms of safety, the regimen was well tolerated without any unexpected safety findings. We, as an expert analysis, we did the pre-planned serial ctDNA analysis and the AI-powered whole slide image analysis. So this will represent also the AI-powered whole slide image analysis, which quantified the HER2-3 positive tumor cell proportion at the whole slide level, and also classified the immune phenotype based on the lymphocyte spatial distribution. Actually, the response rate was consistent regardless of the HER2-IHC status. But when we did the AI-powered HER2 analysis, patients with the higher HER2-3 positive tumor cell proportion at the whole slide level, they had a greater response rate and numerically longer PFS. And also in terms of the immune phenotype, patients with the immune-excluded phenotype had longer PFS compared to the immune-desert phenotype. So this kind of exploratory analysis, but it may help us to better understand the HER2 biology and its correlation with tumor immune microenvironment in the biliary cancer and may refine the future of patient selection. So overall, the HERBOT is the first prospective study to demonstrate the feasibility and the increasing activity of the HER2-targeted chemotherapy in the first-line setting of the HER2-positive biliary cancer. This trial research supports us to integrate the HER2-targeted strategies in the early treatment line and also provides a strong rationale in the currently ongoing global phase 3 trials.

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