November 3rd, 2026
Summary by Catlin Nalley
Patients with previously untreated advanced biliary tract cancer (BTC) who received ivonescimab plus chemotherapy experienced significant improvements in overall (OS) and progression-free survival (PFS) as well as objective response rate (ORR) compared to those who were treated with durvalumab plus chemotherapy, according to findings from the phase III HARMONi-GI1 trial presented during the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid (Abstract LBA8).
Data showed that patients in the ivonescimab plus gemcitabine and cisplatin cohort had a median OS of 14.9 months, compared with 12.1 months among those treated with durvalumab plus the same chemotherapy regimen. The difference represented a 25% reduction in the hazard of death with the investigational combination (HR: 0.75; 95% CI: 0.61–0.92; P=0.0031).
“Advanced BTC remains a disease with substantial unmet clinical need. Most patients are not candidates for curative surgery, and outcomes with systemic therapy remain limited,” noted study author Jian Zhou, MD, PhD, President of Zhongshan Hospital, Shanghai, China, during his ESMO presentation.
Durvalumab, a programmed death-ligand 1 (PD-L1) inhibitor, combined with chemotherapy (gemcitabine and cisplatin) became an established first-line treatment following results from the phase III TOPAZ-1 trial, which demonstrated improved survival compared with chemotherapy alone, according to Zhou.
Ivonescimab is a bispecific antibody designed to target programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF). By combining immune checkpoint inhibition with VEGF blockade, the agent is intended to address complementary mechanisms involved in tumor growth and immune evasion.
Zhou and colleagues conducted the current study to evaluate the efficacy and safety of ivonescimab plus chemotherapy compared with durvalumab plus chemotherapy as first-line treatment for advanced BTC. Findings from the preplanned interim analysis are reported below.
Study Methodology
HARMONi-GI1, a randomized, controlled, double-blind phase III trial conducted in China, enrolled 682 patients with unresectable locally advanced or metastatic BTC.
Eligible patients were randomly assigned to ivonescimab plus chemotherapy (n=340) and durvalumab plus chemotherapy (n=342). Both groups received gemcitabine and cisplatin every 3 weeks for eight cycles, followed by maintenance treatment with their assigned antibody. Randomization was stratified according to disease status—locally advanced or metastatic—and primary tumor location: intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer.
OS was the primary endpoint. Key secondary endpoints included PFS and ORR. The prespecified hierarchical testing procedure evaluated OS first, followed by PFS and ORR. The reported results came from a planned interim analysis after 363 OS events, with follow-up sufficient to provide an informative assessment of survival outcomes.
Primary Outcomes & Safety
Ivonescimab plus chemotherapy significantly improved OS when compared with durvalumab plus chemotherapy. As highlighted above, median OS was 14.9 months in the ivonescimab arm versus 12.1 months in the durvalumab arm.
The combination also significantly improved PFS. Median PFS was 8.4 months with ivonescimab plus chemotherapy compared with 5.8 months with durvalumab plus chemotherapy, representing a 39% reduction in the hazard of disease progression or death (HR: 0.61; 95% CI: 0.51–0.72; P<0.0001).
ORR was 53.8% with ivonescimab plus chemotherapy and 32.5% with durvalumab plus chemotherapy (P<0.0001). Investigators reported higher ORRs with ivonescimab across the primary tumor location subgroups, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
Subgroup analyses also showed that OS and PFS outcomes favored ivonescimab across the prespecified subgroups. These included groups defined by age, sex, Eastern Cooperative Oncology Group performance status, disease status (locally advanced or metastatic), primary tumor location, metastatic-site characteristics, and extent of disease.
Zhou and colleagues also reported that subsequent antitumor therapy was more common among patients in the durvalumab-plus-chemotherapy arm than in the ivonescimab-plus-chemotherapy arm (45.9% versus 31.8%, respectively), a difference of 14.1 percentage points.
At the planned interim analysis, 363 OS events had occurred, representing 81.6% maturity for the primary endpoint. The study met its primary endpoint of OS and both key secondary endpoints, PFS and ORR.
The safety profile of ivonescimab plus chemotherapy was described as manageable, despite longer treatment exposure in the investigational arm (median 7.8 versus 5.7 months). Hematologic toxicities were among the most frequently reported treatment-emergent adverse events in both groups.
No new safety signals were identified for ivonescimab. The research team also reported that immune-related adverse events were broadly similar between treatment arms, with no immune-related adverse events resulting in death. VEGF-related adverse events, including proteinuria and hypertension, were generally low grade, and bleeding risk was considered manageable.
Implications for Clinical Practice
HARMONi-GI1 met its primary endpoint and both key secondary endpoints, demonstrating statistically significant improvements in OS, PFS, and ORR with ivonescimab plus chemotherapy compared with durvalumab plus chemotherapy in previously untreated advanced BTC. The findings support further evaluation of ivonescimab as a potential first-line treatment option.
“HARMONi-GI1 is the first phase III trial in BTC to show statistically significant and clinically meaningful improvement in overall survival over durvalumab plus chemotherapy in a Chinese population,” Zhou concluded. “[These] results support ivonescimab plus chemotherapy as a new standard of care for first-line BTC patients.”
Patients with previously untreated advanced biliary tract cancer (BTC) who received ivonescimab plus chemotherapy experienced significant improvements in overall (OS) and progression-free survival (PFS) as well as objective response rate (ORR) compared to those who were treated with durvalumab plus chemotherapy, according to findings from the phase III HARMONi-GI1 trial presented during the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid (Abstract LBA8).
Data showed that patients in the ivonescimab plus gemcitabine and cisplatin cohort had a median OS of 14.9 months, compared with 12.1 months among those treated with durvalumab plus the same chemotherapy regimen. The difference represented a 25% reduction in the hazard of death with the investigational combination (HR: 0.75; 95% CI: 0.61–0.92; P=0.0031).
“Advanced BTC remains a disease with substantial unmet clinical need. Most patients are not candidates for curative surgery, and outcomes with systemic therapy remain limited,” noted study author Jian Zhou, MD, PhD, President of Zhongshan Hospital, Shanghai, China, during his ESMO presentation.
Durvalumab, a programmed death-ligand 1 (PD-L1) inhibitor, combined with chemotherapy (gemcitabine and cisplatin) became an established first-line treatment following results from the phase III TOPAZ-1 trial, which demonstrated improved survival compared with chemotherapy alone, according to Zhou.
Ivonescimab is a bispecific antibody designed to target programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF). By combining immune checkpoint inhibition with VEGF blockade, the agent is intended to address complementary mechanisms involved in tumor growth and immune evasion.
Zhou and colleagues conducted the current study to evaluate the efficacy and safety of ivonescimab plus chemotherapy compared with durvalumab plus chemotherapy as first-line treatment for advanced BTC. Findings from the preplanned interim analysis are reported below.
Study Methodology
HARMONi-GI1, a randomized, controlled, double-blind phase III trial conducted in China, enrolled 682 patients with unresectable locally advanced or metastatic BTC.
Eligible patients were randomly assigned to ivonescimab plus chemotherapy (n=340) and durvalumab plus chemotherapy (n=342). Both groups received gemcitabine and cisplatin every 3 weeks for eight cycles, followed by maintenance treatment with their assigned antibody. Randomization was stratified according to disease status—locally advanced or metastatic—and primary tumor location: intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer.
OS was the primary endpoint. Key secondary endpoints included PFS and ORR. The prespecified hierarchical testing procedure evaluated OS first, followed by PFS and ORR. The reported results came from a planned interim analysis after 363 OS events, with follow-up sufficient to provide an informative assessment of survival outcomes.
Primary Outcomes & Safety
Ivonescimab plus chemotherapy significantly improved OS when compared with durvalumab plus chemotherapy. As highlighted above, median OS was 14.9 months in the ivonescimab arm versus 12.1 months in the durvalumab arm.
The combination also significantly improved PFS. Median PFS was 8.4 months with ivonescimab plus chemotherapy compared with 5.8 months with durvalumab plus chemotherapy, representing a 39% reduction in the hazard of disease progression or death (HR: 0.61; 95% CI: 0.51–0.72; P<0.0001).
ORR was 53.8% with ivonescimab plus chemotherapy and 32.5% with durvalumab plus chemotherapy (P<0.0001). Investigators reported higher ORRs with ivonescimab across the primary tumor location subgroups, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
Subgroup analyses also showed that OS and PFS outcomes favored ivonescimab across the prespecified subgroups. These included groups defined by age, sex, Eastern Cooperative Oncology Group performance status, disease status (locally advanced or metastatic), primary tumor location, metastatic-site characteristics, and extent of disease.
Zhou and colleagues also reported that subsequent antitumor therapy was more common among patients in the durvalumab-plus-chemotherapy arm than in the ivonescimab-plus-chemotherapy arm (45.9% versus 31.8%, respectively), a difference of 14.1 percentage points.
At the planned interim analysis, 363 OS events had occurred, representing 81.6% maturity for the primary endpoint. The study met its primary endpoint of OS and both key secondary endpoints, PFS and ORR.
The safety profile of ivonescimab plus chemotherapy was described as manageable, despite longer treatment exposure in the investigational arm (median 7.8 versus 5.7 months). Hematologic toxicities were among the most frequently reported treatment-emergent adverse events in both groups.
No new safety signals were identified for ivonescimab. The research team also reported that immune-related adverse events were broadly similar between treatment arms, with no immune-related adverse events resulting in death. VEGF-related adverse events, including proteinuria and hypertension, were generally low grade, and bleeding risk was considered manageable.
Implications for Clinical Practice
HARMONi-GI1 met its primary endpoint and both key secondary endpoints, demonstrating statistically significant improvements in OS, PFS, and ORR with ivonescimab plus chemotherapy compared with durvalumab plus chemotherapy in previously untreated advanced BTC. The findings support further evaluation of ivonescimab as a potential first-line treatment option.
“HARMONi-GI1 is the first phase III trial in BTC to show statistically significant and clinically meaningful improvement in overall survival over durvalumab plus chemotherapy in a Chinese population,” Zhou concluded. “[These] results support ivonescimab plus chemotherapy as a new standard of care for first-line BTC patients.”