Clinical Summary: 

• Design/Population: This phase 3 trial evaluated ivonescimab plus gemcitabine and cisplatin versus durvalumab plus gemcitabine and cisplatin in patients with previously untreated, unresectable locally advanced or metastatic biliary tract cancer.

• Key Outcomes: Ivonescimab plus chemotherapy significantly improved overall survival, progression-free survival, and objective response rate compared with durvalumab plus chemotherapy, reducing the risk of death by 25% and the risk of disease progression or death by 39%. No new safety signals were identified.

• Clinical Relevance: These findings support ivonescimab plus chemotherapy as a potential new first-line treatment option for advanced ,biliary tract cancer, demonstrating improved survival and antitumor activity compared with a durvalumab-based standard regimen.

Results from a phase 3 trial demonstrated that ivonescimab plus gemcitabine and cisplatin significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared with durvalumab plus chemotherapy in patients with advanced biliary tract cancer, supporting the PD-1/VEGF bispecific antibody as a potential new first-line treatment option.

These findings were presented by Jian Zhou, MD, PhD, Zhongshan Hospital at Fudan University in Shanghai, China, ​​​​​during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress.

In this randomized phase 3 trial, 682 patients with unresectable locally advanced or metastatic biliary tract cancer were randomized 1:1 to receive ivonescimab plus gemcitabine and cisplatin (n = 340) or durvalumab plus gemcitabine and cisplatin (n = 342).

Patients received their assigned immunotherapy in combination with gemcitabine and cisplatin every 3 weeks for 8 cycles, followed by maintenance treatment with ivonescimab or durvalumab. Randomization was stratified according to disease status (locally advanced or metastatic) and primary tumor location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer).

The primary end point was OS. Key secondary end points included PFS and ORR. The reported findings were from a prespecified interim analysis.

At a median follow-up of 14.3 months, median OS was 14.9 months in the ivonescimab plus chemotherapy arm and 12.1 months in the durvalumab plus chemotherapy arm, reducing the risk of death by 25% (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61 to 0.92; P = .0031).

A significant PFS benefit was also observed with ivonescimab plus chemotherapy. Median PFS was 8.4 months and 5.8, respectively, corresponding to a 39% reduction in the risk of disease progression or death (HR, 0.61; 95% CI, 0.51 to 0.72; P < .0001).

The ORR was significantly higher with ivonescimab plus chemotherapy, at 53.8% compared with 32.5% with durvalumab plus chemotherapy (P < .0001).

These findings demonstrate that combining PD-1 and VEGF inhibition with chemotherapy improved survival and antitumor activity compared with durvalumab-based chemoimmunotherapy in the first-line treatment of advanced biliary tract cancer.

The safety profile of ivonescimab plus chemotherapy was reported to be manageable, with hematologic toxicities representing the most common treatment-emergent adverse events.

No new safety signals were identified with ivonescimab. Detailed adverse event rates, including grade ≥3 toxicities and treatment discontinuations, were not provided in the interim analysis.

As Dr Zhou concluded, "these results support ivonescimab plus chemo as a potential new first-line standard of care for advanced biliary tract cancer." 

Source: 

Zhou J, et al. Ivonescimab plus chemotherapy versus durvalumab plus chemotherapy as first-line treatment for advanced biliary tract cancer: A randomized, controlled, double-blinded, phase 3 trial (HARMONi-GI1). Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA8.