First-Line Ivonescimab Plus Chemotherapy Meets OS End Point in Advanced Biliary Tract Cancer

Ivonescimab (SMT112; AK112) in combination with gemcitabine plus cisplatin generated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with durvalumab (Imfinzi) plus gemcitabine and cisplatin in patients with unresectable locally advanced or metastatic biliary tract cancer who had not received prior systemic therapy, meeting the primary end point of the single-region phase 3 HARMONi-GI1 trial (NCT06591520) at a prespecified interim analysis.^1,2

The ivonescimab-based regimen also met the key secondary end points of progression-free survival (PFS) and objective response rate (ORR), according to news releases from Summit Therapeutics and Akeso. The OS benefit was identified at a prespecified interim analysis assessed by an independent data monitoring committee (IDMC), and Akeso characterized HARMONi-GI1 as the first phase 3 study in BTC to demonstrate a statistically significant OS benefit vs an anti–PD-(L)1 antibody plus chemotherapy, which international guidelines recommend as a preferred first-line standard of care.²

Detailed results from HARMONi-GI1, including safety and efficacy data, are expected to be presented at an upcoming medical congress and published in a peer-reviewed journal.¹

“The positive result of HARMONi-GI1 marks the first positive phase 3 study for ivonescimab in gastrointestinal tumors, following four positive phase 3 results in lung cancer,” Michelle Xia, PhD, founder, chairwoman, president, and chief executive officer of Akeso, stated in a news release.² “The breakthrough clinical value of ivonescimab is now expanding from lung cancer to a broader range of solid tumors. We look forward to making this innovative therapy available to patients worldwide as soon as possible.”

Ivonescimab, a PD-1 x VEGF bispecific antibody, is approved and commercially available in China for indications in non–small cell lung cancer (NSCLC), but it remains investigational and is not approved by any regulatory authorities in the United States and Europe.¹

How was the HARMONi-GI1 trial designed?

HARMONi-GI1 was a randomized, double-blind, multicenter phase 3 study conducted at sites in China that enrolled 682 patients with histologically or cytologically confirmed, unresectable locally advanced or metastatic bilary tract cancer.^2,3

Eligible patients needed to be 18 to 75 years of age with an ECOG performance status of 0 or 1.³ No prior systemic anti-tumor therapy for advanced disease was permitted, and patients needed to have measurable disease per RECIST 1.1 criteria. Patients with active central nervous system metastases, active autoimmune disease requiring systemic treatment within the prior 2 years, or active hepatitis B or C were among those excluded.

Patients were randomly assigned to receive ivonescimab intravenously every 3 weeks or durvalumab at 1500 mg every 3 weeks, each combined with gemcitabine at 1000 mg/m² and cisplatin at 25 mg/m² administered on days 1 and 8 every 3 weeks for up to 8 cycles.

The primary end point was OS. Secondary end points included PFS, ORR, duration of response, disease control rate, time to response, and safety.

"We are delighted the phase 3 clinical study of ivonescimab in combination with chemotherapy vs durvalumab in combination with chemotherapy for the first-line treatment of biliary tract cancer has achieved a statistically significant positive OS result. This is a major breakthrough for the treatment of biliary tract cancer,” Xia also stated in a news release.² "We sincerely thank the investigators, study teams, and patients who made HARMONi-GI1 possible. Their important contributions bring us closer to an innovative, safe, and highly effective new treatment option against this aggressive cancer.”

References

1. Ivonescimab plus chemotherapy demonstrates statistically significant overall survival benefit compared to durvalumab plus chemotherapy in first-line advanced biliary tract cancer in single-region trial conducted by Akeso in China. News release. Summit Therapeutics. August 25, 2026. Accessed August 26, 2026. https://smmttx.com/news/press-releases/news-details/2026/Ivonescimab-Plus-Chemotherapy-Demonstrates-Statistically-Significant-Overall-Survival-Benefit-Compared-to-Durvalumab-Plus-Chemotherapy-in-First-Line-Advanced-Biliary-Tract-Cancer-in-Single-Region-Trial-Conducted-by-Akeso-in-China/default.aspx
2. Ivonescimab plus chemotherapy demonstrates significant overall survival benefit versus durvalumab plus chemotherapy in first-line biliary tract cancer: HARMONi-GI1 meets primary endpoint. News release. Akeso, Inc. August 25, 2026. Accessed August 26, 2026. https://www.prnewswire.com/news-releases/ivonescimab-plus-chemotherapy-demonstrates-significant-overall-survival-benefit-versus-durvalumab-plus-chemotherapy-in-first-line-biliary-tract-cancer-harmoni-gi1-meets-primary-endpoint-302859811.html
3. A randomized, controlled, multi-center phase III study of AK112 combined with gemcitabine plus cisplatin versus durvalumab combined with gemcitabine plus cisplatin as the first-line treatment for patients with advanced biliary tract cancer. ClinicalTrials.gov. Updated January 21, 2026. Accessed August 26, 2026. https://clinicaltrials.gov/study/NCT06591520