Phase 3 trial — HARMONi-GI1 (NCT06591520), ESMO 2026 Presidential Symposium China — ivonescimab approved for lung cancer U.S., EU, Japan — not yet approved; U.S. phase 2/3 trial in preparation
Here is news on a new drug for biliary tract cancer. In first-line treatment of advanced biliary tract cancer that cannot be removed by surgery, patients who received ivonescimab with chemotherapy lived longer than those given the current standard, durvalumab (Imfinzi) with chemotherapy. Median overall survival was 14.9 versus 12.1 months, with a 25% lower risk of death. The results come from the Chinese phase 3 HARMONi-GI1 trial, presented at the Presidential Symposium of the European Society for Medical Oncology congress (ESMO 2026) in Madrid in October 2026.
What is new: immunotherapy and blood-vessel blocking in one drug
Biliary tract cancer arises in the bile ducts, which carry bile from the liver, and in the gallbladder, which stores it. By location it is divided into intrahepatic cholangiocarcinoma (inside the liver), extrahepatic cholangiocarcinoma (outside the liver) and gallbladder cancer. Early symptoms are few, so many patients are diagnosed when surgery is no longer possible, which makes progress in drug treatment especially important.
The first-line treatment used in many countries today adds an immunotherapy drug to two chemotherapy drugs, gemcitabine and cisplatin. Durvalumab with this chemotherapy is a leading standard and is covered by insurance in Japan. HARMONi-GI1 matters because it compared the new drug head to head with this standard.
Ivonescimab is a bispecific antibody: one molecule that hits two targets. One arm releases PD-1, a brake on immune cells, helping them attack cancer; the other blocks VEGF, a signal tumors use to grow new blood vessels. It was developed by the Chinese company Akeso, and rights outside China, including the U.S., Europe and Japan, are held by Summit Therapeutics in the U.S. In Summit's territories it is also known by the development name SMT112.
Who is eligible: advanced biliary tract cancer starting first drug treatment
Patients in HARMONi-GI1 met these criteria:
- Locally advanced or metastatic biliary tract cancer that could not be removed surgically, or that recurred after curative treatment
- No previous systemic drug therapy for advanced disease (first-line)
- Able to carry out daily activities independently (ECOG performance status 0 or 1)
Both groups received gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m²) on days 1 and 8 every 3 weeks. One group added ivonescimab 20 mg/kg and the other added durvalumab 1,500 mg. Chemotherapy was given for up to 8 cycles, followed by maintenance with the antibody alone.
HARMONi-GI1 results: median survival of 14.9 months
HARMONi-GI1 was a double-blind, randomized phase 3 trial run at multiple hospitals in China. It assigned 682 patients to ivonescimab (340) or durvalumab (342), with overall survival as the primary endpoint. The results below are from a prespecified interim analysis at a median follow-up of 14.3 months.
| Measure | Ivonescimab + chemo | Durvalumab + chemo |
|---|---|---|
| Median overall survival | 14.9 months | 12.1 months |
| Hazard ratio for death | 0.75 (95% CI 0.61–0.92) — 25% lower risk of death | |
| 12-month survival | 59.7% | 50.7% |
| 18-month survival | 44.0% | 32.5% |
| Median progression-free survival | 8.4 months | 5.8 months |
| Hazard ratio for progression | 0.61 (95% CI 0.51–0.72) | |
| Response rate | 53.8% | 32.5% |
| Disease control rate | 91.5% | 77.8% |
Source: OncLive coverage of the ESMO 2026 presentation (abstract LBA8) and the Summit Therapeutics release (2026-10-25). Response rate is the share of patients whose tumors shrank by a set amount; disease control rate is the share whose tumors shrank or did not grow.
At 18 months, 44.0% of patients were alive, 11.5 percentage points more than with durvalumab, and more than half saw their tumors shrink. The presenting investigators from Zhongshan Hospital in Shanghai said the results could change the standard for first-line treatment of advanced biliary tract cancer.
By tumor location, the benefit was clearest in intrahepatic cholangiocarcinoma, the largest group (394 patients), with a hazard ratio of 0.63. Extrahepatic cholangiocarcinoma (0.94) and gallbladder cancer (0.95) had fewer patients, so more data are needed to judge survival there, but tumor shrinkage was higher with ivonescimab in all three (intrahepatic 54.0% vs 30.1%, extrahepatic 47.7% vs 36.4%, gallbladder 58.4% vs 35.0%).
Side effects and management: regular checks of blood pressure, urine and blood counts
Because both groups also received chemotherapy, blood-related side effects were most common. Grade 3–4 neutropenia occurred in 54.6% with ivonescimab and 41.3% with durvalumab. Grade 3–4 adverse events overall were 82.0% versus 72.3%, but patients on ivonescimab stayed on treatment longer (7.8 versus 5.7 months). Serious adverse events were similar (43.4% vs 43.7%), and fewer patients stopped treatment because of side effects (3.5% vs 5.6%).
As expected for a VEGF-blocking drug, proteinuria (32.2% vs 11.8%), high blood pressure (15.0% vs 2.4%) and bleeding (9.7% vs 6.5%) were more frequent, mostly grade 1–2. Immune-related side effects were similar (26.3% vs 22.1%); grade 3 or higher occurred in 4.1% in each group, with no deaths from them. Measuring and recording blood pressure at home, keeping up with scheduled urine and blood tests, and contacting the care team promptly about fever or bleeding that does not stop are the basics of management.
Where it is available: a follow-up trial is starting in the U.S.
- China: Ivonescimab was first approved in May 2024 and is marketed for non-small cell lung cancer. As of the check date, no approval for biliary tract cancer has been announced.
- United States: It is an investigational drug. The ECOG-ACRIN cancer research group will run a phase 2/3 trial (EA2251) comparing ivonescimab plus chemotherapy with pembrolizumab or durvalumab plus chemotherapy, with U.S. site activation expected from the fourth quarter of 2026. Its primary endpoint is again overall survival.
- Japan and Europe: Both are in Summit's territories, but no filing schedule for biliary tract cancer has been announced. In Japan, the current standard of gemcitabine and cisplatin plus immunotherapy is available under insurance.
Because HARMONi-GI1 enrolled only patients in China, results from the U.S. trial in a more diverse population are likely to be an important basis for approval decisions. More news on new cancer drugs is in By cancer type, and tips on reading Japanese medical information are in Other medical information.
What to check and questions for your doctor
- Is my cancer intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma or gallbladder cancer?
- Which first-line options can I receive now (durvalumab or pembrolizumab with chemotherapy), and what benefit can I expect?
- Would genetic tests such as FGFR2 or IDH1 help with later treatment choices?
- Are there centers where I could join a clinical trial of new drugs such as ivonescimab?
- When should I call if my blood pressure rises or my urine becomes very foamy?
Frequently asked questions
What is ivonescimab, the new biliary tract cancer drug?
It is a bispecific antibody that blocks both PD-1, a brake on immune cells, and VEGF, a signal that feeds tumor blood vessels, in a single molecule. It was developed by Akeso and is approved in China for lung cancer.
How well did it work in HARMONi-GI1?
Median overall survival was 14.9 months versus 12.1 months with durvalumab, a 25% lower risk of death. Median progression-free survival was 8.4 versus 5.8 months, and the response rate was 53.8% versus 32.5%.
What are the side effects of ivonescimab?
Blood-related effects such as low neutrophil counts were most common. Proteinuria (32.2%), high blood pressure (15.0%) and bleeding (9.7%) were more frequent, mostly mild. Only 3.5% stopped treatment because of side effects, versus 5.6% with durvalumab.
Is ivonescimab available in Japan or the U.S.?
As of 2026-10-28 it is not yet approved in the U.S., Europe or Japan. In the U.S., a phase 2/3 trial (EA2251) comparing the same first-line options is expected to start enrolling in the fourth quarter of 2026.
Related articles: FDA approves daraxonrasib for pancreatic cancer · Savolitinib for Tagrisso resistance · All articles by cancer type
Sources
- OncLive — Ivonescimab plus chemotherapy improves OS vs durvalumab plus chemotherapy in first-line biliary tract cancer (ESMO 2026, LBA8)
onclive.com
Checked: 2026-10-28 - EMJ — Ivonescimab improves survival in biliary tract cancer: ESMO 2026 (2026-10-27)
emjreviews.com
Checked: 2026-10-28 - Summit Therapeutics — Ivonescimab plus chemotherapy demonstrates overall survival superiority compared to durvalumab plus chemotherapy in first-line advanced biliary tract cancer in HARMONi-GI1 (2026-10-25)
stocktitan.net (Business Wire)
Checked: 2026-10-28 - Summit Therapeutics — HARMONi-GI1 to be showcased in Presidential Symposium at ESMO 2026 (2026-09-22)
businesswire.com
Checked: 2026-10-28 - OncLive — First-line ivonescimab plus chemotherapy meets OS end point in advanced biliary tract cancer (2026-08-26)
onclive.com
Checked: 2026-10-28 - ClinicalTrials.gov — NCT06591520: HARMONi-GI1, ivonescimab plus chemotherapy versus durvalumab plus chemotherapy in advanced biliary tract cancer
clinicaltrials.gov/study/NCT06591520
Checked: 2026-10-28
Written by the FTH editorial team. Sources checked 2026-10-28 · Medical review: not applicable
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your medical team.
