Positive Overall Survival Results from the Phase III HARMONi-GI1 Trial of Ivonescimab Plus Chemotherapy Versus Durvalumab Plus Chemotherapy in First-Line Biliary Tract Cancer Presented at the ESMO 2026 Presidential Symposium

HONG KONG, Oct. 25, 2026 /PRNewswire/ -- Akeso, Inc. (HKEX: 9926.HK) today announced the presentation of results from the randomized, controlled, double-blind, multicenter, registrational Phase III HARMONi-GI1 trial (AK112-309). The study evaluated first-in-class ivonescimab plus chemotherapy versus durvalumab (PD-L1) plus chemotherapy as first-line treatment for patients with advanced biliary tract cancer (BTC) and was presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain.

In a prespecified interim analysis reviewed by the Independent Data Monitoring Committee (IDMC), HARMONi-GI1 met its primary endpoint of overall survival (OS), with the ivonescimab plus chemotherapy arm demonstrating statistically significant and clinically meaningful improvement over the control arm. The trial also met all key secondary endpoints, including progression-free survival (PFS) and objective response rate (ORR).

On the strength of these findings, HARMONi-GI1 was selected as a Late-Breaking Abstract (LBA) for oral presentation and included in the official ESMO press program. Principal investigator Professor Jian Zhou, Academician of the Chinese Academy of Sciences, President of Zhongshan Hospital, Fudan University, presented the detailed clinical results of this study to the global oncology community during Presidential Symposium II.

Durvalumab combined with chemotherapy is currently the preferred first-line immunotherapy regimen recommended by both domestic and international guidelines and is widely regarded as the standard of care. HARMONi-GI1 is the first Phase III trial in biliary tract cancer to demonstrate statistically significant and clinically meaningful positive results in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) versus this standard of care regimen (PD-L1 monoclonal antibody plus chemotherapy), marking a major milestone in the treatment of this challenging disease.

The results showed that, compared with durvalumab plus chemotherapy, first-line treatment with ivonescimab plus chemotherapy significantly prolonged overall survival in patients with BTC, meeting the prespecified threshold for statistical significance and delivering clinically meaningful benefit. Prespecified subgroup analyses showed a generally consistent trend of OS benefit.

ITT Population: Median OS of 14.9 Months with a 25% Reduction in the Risk of Death, Demonstrating a Significant Long-Term Survival Tail Effect

In the intent-to-treat (ITT) population, ivonescimab plus chemotherapy significantly prolonged overall survival compared with durvalumab plus chemotherapy. Median OS was 14.9 months versus 12.1 months (HR=0.75; 95% CI: 0.61–0.92), corresponding to a 25% reduction in the risk of death (P=0.0031). (For reference, the TOPAZ-1 study published in 2022 reported a median OS of 12.8 months with durvalumab plus chemotherapy versus 11.5 months with chemotherapy alone [HR=0.80]; based on the outcome of that trial, durvalumab plus chemotherapy became an international first-line standard of care.)

The survival benefit with ivonescimab continued to widen over time relative to the control arm, reflecting a more durable and clinically meaningful long-term survival advantage. Twelve-month OS rates were 59.7% versus 50.7%, and 18-month OS rates were 44.0% versus 32.5%, underscoring a pronounced long-term survival tail effect in the ivonescimab arm.

Following study discontinuation, a substantially lower proportion of patients in the ivonescimab arm received any anti-tumor therapy compared with the durvalumab arm (31.8% versus 45.9%).

ITT Population: Ivonescimab Significantly Prolonged PFS, with a Median PFS of 8.4 Months and a 39% Reduction in the Risk of Disease Progression or Death

The study met its key secondary endpoint of progression-free survival. In the ITT population, ivonescimab significantly prolonged PFS compared with durvalumab, with a median PFS of 8.4 months versus 5.8 months (HR=0.61; 95% CI: 0.51–0.72; P<0.0001). The 6-month PFS rates were 68.7% versus 49.3%, and nine-month PFS rates were 49.3% versus 31.7% for the ivonescimab and durvalumab arms, respectively.

ITT Population: Ivonescimab Demonstrated Robust and Deep Tumor Responses

The study also met its key secondary endpoint of objective response rate. Ivonescimab showed superior depth of tumor response and disease control compared with durvalumab. ORR was 53.8% versus 32.5%, an absolute difference of 21.3 percentage points (P<0.0001). Disease control rates (DCR) were 91.5% and 77.8%, respectively.

Consistent OS and PFS Benefits Across Subgroups with Ivonescimab

Among patients with an ECOG performance status of 1 (ECOG PS 1), ivonescimab demonstrated a significant survival benefit versus durvalumab (OS HR, 0.71 [95% CI, 0.56–0.91]; PFS HR, 0.57 [95% CI, 0.47–0.70]). Similarly, among older patients (aged ≥65 years), ivonescimab showed a significant survival benefit compared with durvalumab (OS HR, 0.67 [95% CI, 0.47–0.95]; PFS HR, 0.53 [95% CI, 0.39–0.71]).

Favorable Overall Safety Profile with No New Safety Signals

The safety profile of ivonescimab plus chemotherapy was manageable, accompanied by longer treatment exposure. The most common adverse events of any grade and of grade 3/4 were hematologic toxicities; no new safety signals were identified.

Incidences of serious adverse events (43.4% versus 43.7%) and of bleeding events of any grade (9.7% versus 6.5%) or grade ≥3 (1.5% versus 1.8%) were similar to those in the durvalumab arm, with no evidence of increased risk of uncontrolled bleeding.

Biliary tract cancer is a highly heterogeneous malignancy arising from the bile ducts and gallbladder and carries a poor prognosis; approximately 50% of patients are diagnosed at an advanced stage, with survival typically less than one year. PD-1/L1 inhibitor plus chemotherapy is the established international first-line treatment for advanced biliary tract cancer, yet the overall survival benefit remains limited. Durvalumab plus chemotherapy is currently regarded as the preferred first-line immuno-oncology regimen recommended by both domestic and international guidelines.

The breakthrough data from HARMONi-GI1 strongly support the potential of ivonescimab plus chemotherapy as a new standard of care for first-line advanced BTC. Furthermore, as the first Phase III study to achieve a positive result in gastrointestinal cancers following multiple Phase III successes in lung cancer, HARMONi-GI1 marks the expansion of ivonescimab's breakthrough clinical value from lung cancer into a broader range of solid tumors. Ivonescimab plus chemotherapy for first-line BTC has been proposed for Priority Review designation by China's National Medical Products Administration (NMPA).

On October 21, 2026, Summit announced a clinical trial collaboration with ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) to evaluate the safety and efficacy of ivonescimab with chemotherapy compared to pembrolizumab or durvalumab plus chemotherapy in a registration-enabling Phase II/III study (EA2251), in the first-line treatment of patients with advanced BTC.

About Ivonescimab
Ivonescimab is a first-in-class PD-1/VEGF bispecific antibody independently developed by Akeso. It is the world's first approved bispecific antibody that combines immuno-oncology and anti-angiogenesis mechanisms in a single molecule, helping to define a new generation of bispecific immuno-oncology therapies. Ivonescimab is also the first therapy to demonstrate positive results in a Phase III head-to-head study against pembrolizumab.

Building on its strong clinical profile in the IO2.0 landscape, Akeso is advancing a comprehensive global development program for ivonescimab across multiple tumor types and treatment settings. As a cornerstone of the Company's IO2.0 + ADC2.0 strategy, ivonescimab aims to help reshape standards of care in major cancers worldwide.

More than 18 Phase III studies of ivonescimab are underway globally, including seven international multi-regional registrational Phase III trials and seven head-to-head studies versus PD-1/PD-L1 therapies. These programs encompass eight registrational or Phase III studies in lung cancer, as well as trials in first-line MSS/pMMR colorectal cancer, first-line PD-L1-positive head and neck squamous cell carcinoma (in combination with ligufalimab versus pembrolizumab), first-line biliary tract cancer (versus pembrolizumab/ durvalumab-based regimen), first-line triple-negative breast cancer, first-line pancreatic cancer, and first-line urothelial carcinoma (versus pembrolizumab plus a Nectin-4 ADC).

Akeso has out-licensed the exclusive rights to develop and commercialize ivonescimab in the United States and Canada, South America, Europe, the Middle East, Africa, and Japan to Summit Therapeutics under an agreement with a total potential value of up to US$5 billion.

About Akeso
Akeso (HKEX: 9926.HK) is a leading biopharmaceutical company committed to the research, development, manufacturing and commercialization of the world's first or best-in-class innovative biological medicines. Founded in 2012, Akeso has built a comprehensive R&D innovation ecosystem anchored by its proprietary Tetrabody antibody technology platform, AI-powered drug R&D platform, Dual-Shield ADC technology platform, Dual-Lock T-cell engager (TCE) technology platform, Tissue-Smart siRNA/mRNA technology platform, and cell therapy technology platforms.

Backed by world-class GMP manufacturing facilities and a highly efficient, integrated commercialization system, Akeso has developed into a globally competitive biopharmaceutical enterprise. Leveraging its fully integrated, multi-functional platform, the Company maintains a robust pipeline of more than 50 innovative assets targeting cancer, autoimmune diseases, inflammation, metabolic disorders, and other major therapeutic areas. Of these, nearly 30 candidates have advanced into clinical trials, including 15 bispecific or multi-specific antibodies and bispecific ADCs. Eight innovative drugs are commercially available, and two additional drugs with three indications are currently under regulatory review for marketing approval.

Akeso is committed to becoming a global leader in biopharmaceuticals through efficient and breakthrough innovation in R&D, developing novel therapies that are first-in-class or best-in-class, and providing better disease solutions for patients around the world.

Forward-Looking Statements
This announcement by Akeso, Inc. (9926.HK, "Akeso") contains "forward-looking statements". These statements reflect the current beliefs and expectations of Akeso's management and are subject to significant risks and uncertainties. These statements are not intended to form the basis of any investment decision or any decision to purchase securities of Akeso. There can be no assurance that the drug candidate(s) indicated in this announcement or Akeso's other pipeline candidates will obtain the required regulatory approvals or achieve commercial success. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the P.R. China, the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Akeso's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Akeso's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Akeso does not undertake any obligation to publicly revise these forward-looking statements to reflect events or circumstances after the date hereof, except as required by law.

SOURCE Akeso, Inc.