Trial: A Phase Ⅲ Clinical Study of HLX22 in Co…

Trial Details

Sponsor: Shanghai Henlius Biotech (industry)

Phase: 3

Start date: Nov. 22, 2024

Planned enrollment: 550

Trial ID: NCT06532006

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: HLX22 (AC101)

Overview

HLX22 (also known as AC101) is an investigational anti‑HER2 monoclonal antibody being developed by Shanghai Henlius under a sublicense from AbClon; the antibody originated from Alligator/Atlas Therapeutics. It is in global phase 3 testing for first‑line HER2‑positive metastatic gastric/gastroesophageal junction (G/GEJ) cancer and has completed a randomized phase 2 study in the same setting. Orphan Drug Designation for gastric cancer has been granted in the United States (March 2025) and European Union (May 2025). (mdanderson.org)

Mechanism of action

HLX22 targets the HER2 extracellular subdomain IV at a binding site distinct from trastuzumab, enabling simultaneous binding with trastuzumab. Dual engagement promotes increased internalization of HER2 homodimers and HER2/EGFR heterodimers (reported increase ~40–80%), leading to deeper blockade of downstream signaling (e.g., STAT3, AKT, p70 S6). Preclinical models of HER2‑positive gastric cancer showed synergistic antitumor activity when HLX22 was combined with trastuzumab. (translational-medicine.biomedcentral.com)

Efficacy

Phase 2 (randomized, double‑blind; NCT04908813) in first‑line HER2‑positive advanced G/GEJ cancer compared HLX22 (15 or 25 mg/kg Q3W) + trastuzumab biosimilar (HLX02) + XELOX vs placebo + HLX02 + XELOX. With median follow‑up of 14.3 months (data cutoff July 30, 2023):
Median PFS (IRRC): 15.1 months in 25 mg/kg arm (HR 0.50, 95% CI 0.17–1.27) and not reached in 15 mg/kg arm (HR 0.10, 95% CI 0.04–0.52) vs 8.2 months in control. Confirmed ORR was similar across arms at initial assessment (77.8%/82.4%/88.9%), but response durability favored HLX22 with higher ORR at weeks 36 and 48 (e.g., week 48: 58.8% in 15 mg/kg arm vs 16.7% in control). Overall survival was not reached in the HLX22 arms at cutoff. (pubmed.ncbi.nlm.nih.gov)
Phase 3 (HLX22‑GC‑301; NCT06532006): ongoing global, double‑blind, randomized study testing HLX22 + trastuzumab + chemotherapy vs trastuzumab + chemotherapy ± pembrolizumab as first‑line therapy for HER2‑positive metastatic G/GEJ cancer; sites include the U.S., Japan, Australia, China and others, with first U.S. patient dosed July 14, 2025. (mdanderson.org)
Other programs: A phase 2 study in China is evaluating HLX22 in combination with trastuzumab deruxtecan for HER2‑low, HR‑positive advanced breast cancer (first patient dosed April 2025). (pharmiweb.com)

Safety

Phase 2 (G/GEJ cancer): Treatment‑related adverse events (TRAEs) occurred in 100.0% (25 mg/kg), 94.1% (15 mg/kg), and 94.4% (control) of patients; serious TRAEs in 27.8%, 5.9%, and 5.6%, respectively. One grade 5 TRAE occurred in the control arm. Overall safety was described as manageable. (ascopubs.org)
Phase 1 (first‑in‑human, dose‑escalation across HER2‑overexpressing solid tumors; n=11): HLX22 up to 25 mg/kg Q3W had no dose‑limiting toxicities or treatment‑related serious AEs; common TEAEs included decreased lymphocyte count (45.5%), decreased WBC count (36.4%), and hypokalemia (36.4%). No objective responses were observed; disease control rate 36.4% (stable disease in 4 patients); median PFS 44 days. (pubmed.ncbi.nlm.nih.gov)

HealthScout AI Analysis

Goal: To determine whether adding HLX22, a humanized anti-HER2 monoclonal antibody, to trastuzumab plus XELOX improves progression-free survival and overall survival compared with trastuzumab plus XELOX with or without pembrolizumab as first-line therapy for HER2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

Patients: Adults ≥18 years with previously untreated, HER2-positive (IHC 3+ or IHC 2+ with ISH/FISH+ by central testing) locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, measurable disease per RECIST v1.1, ECOG 0–1, adequate organ function, and life expectancy ≥6 months. Key exclusions include prior HER2-targeted therapy, progression within 6 months after perioperative therapy, active GI bleeding, CNS metastases, LVEF <55%, and severe monoclonal antibody hypersensitivity.

Design: Multiregion, randomized, double-blind, active-controlled phase 3 trial with 1:1 allocation; approximately 550 participants. Treatment continues until loss of clinical benefit, unacceptable toxicity, death, withdrawal, or per protocol criteria. Blinding applies to HLX22 versus placebo; pembrolizumab use is allowed per protocol in the control arm and mirrored with placebo in the experimental arm to preserve blinding.

Treatments: Experimental: HLX22 15 mg/kg Q3W plus trastuzumab and XELOX, with placebo for pembrolizumab as applicable. Control: placebo for HLX22 plus trastuzumab and XELOX, with or without pembrolizumab Q3W per protocol. HLX22 is a humanized IgG1 monoclonal antibody targeting HER2, binding a domain IV epitope that does not overlap with trastuzumab, enabling dual engagement. Preclinical and early clinical data suggest enhanced HER2 internalization and signaling inhibition with synergistic antitumor activity when combined with trastuzumab. In a randomized phase 2 study in first-line HER2-positive G/GEJ cancer, HLX22 plus trastuzumab biosimilar and XELOX improved independent review PFS versus control with manageable toxicity, supporting phase 3 evaluation.

Outcomes: Co-primary endpoints are PFS by IRRC per RECIST v1.1 and overall survival. Secondary endpoints include investigator-assessed PFS, ORR by IRRC and investigator per RECIST v1.1, and safety/adverse events. Follow-up for efficacy and safety is up to 5 years.

Burden on patient: Moderate. Visits every 3 weeks for IV infusions of trastuzumab and either HLX22 or placebo, plus oxaliplatin and oral capecitabine, align with standard XELOX-based care. Imaging at regular intervals per RECIST and routine labs, cardiac monitoring for HER2-directed therapy (e.g., periodic echocardiogram/MUGA), and adverse event assessments are expected. There are no intensive pharmacokinetic schedules or mandatory serial biopsies described; however, the double-blind design with combination IV therapy and long follow-up adds visit frequency and monitoring beyond oral-only regimens.

Last updated: Oct 2025

Eligibility

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Sites (88)

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Concord Repatriation General Hospital

Concord, Sydney, Australia

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Peninsula Health-Frankston hospital

Frankston, Melbourne, 3940, Australia

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St. Vincent Hospital Melbourne

Fitzroy, Melbourne, 3065, Australia

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University of the Sunshine Coast Clinical Trials, Sunshine Coast Haematology and Oncology Clinic

Sunshine Coast, Queensland, 4556, Australia

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Central Coast Local Health District (Gosford and Wyong Hospital)

Gosford, Sydney, 2250, Australia

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GenesisCare Research

Campbelltown, Sydney, 2560, Australia

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Macquarie University

North Ryde, Sydney, 2109, Australia

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Centro de Oncologia de Precision

Santiago, Santiago Metropolitan, 7560908, Chile

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Instituto del Cancer RedSalud Vitacura

Santiago, Santiago Metropolitan, 7630000, Chile

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Affiliated Hospital of Youjiang Medical University for Nationalities

Baise City, China

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Cancer Hospital Affiliated to Xinjiang Medical University

Ürümqi, China

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Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

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Cancer Hospital of Shandong First Medical University

Jinan, China

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Fujian Cancer Hospital

Fuzhou, China

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Gansu Provincial Cancer Hospital

Lanzhou, China

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Gansu Provincial Hospital

Lanzhou, China

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General Hospital of Ningxia Medical University

Yinchuan, China

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Harbin Medical University Cancer Hospital

Harbin, China

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Henan Cancer Hospital

Zhengzhou, China

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Heping Hospital Affiliated to Changzhi Medical College

Changzhi, China

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Hunan Cancer Hospital

Changsha, China

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Liaoning Medical University Cancer Institute & Hospital

Shenyang, China

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Liuzhou Workers' Hospital

Liuzhou, China

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Mianyang Central Hospital

Mianyang, China

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Nanjing Drum Tower Hospital

Nanjing, China

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Peking Union Medical College Hospital

Beijing, China

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Qinghai University Affiliated Hospital

Xining, China

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Renji Hospital,Shanghai Jiao Tong University School of Medicine

Shanghai, China

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Shanxi Cancer Hospital

Taiyuan, China

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Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital

Chengdu, China

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Sir Run Run Shaw Hospital (SRRSH), affiliated with the Zhejiang University School of Medicine

Hangzhou, China

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The Affiliated Hospital of Qingdao University

Qingdao, China

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The Central Hospital of Shaoyang

Shaoyang, China

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The First Affiliated Hospital of Anhui Medical University

Hefei, China

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The First Affiliated Hospital of Bengbu Medical University

Bengbu, China

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The First Affiliated Hospital of Chongqing Medical University

Chongqing, China

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The First Affiliated Hospital of Henan University of Science

Luoyang, China

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The First Affiliated Hospital of Nanchang University

Nanchang, China

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The First Affiliated Hospital of Xiamen University

Xiamen, China

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The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

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The First Affiliated Hospital, Zhejiang University School of Medic

Hangzhou, China

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The First Hospital Of Lanzhou University

Lanzhou, China

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The First Hospital of Jilin University

Changchun, China

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The Second Hospital of Anhui Medical University

Hefei, China

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The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, China

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Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

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West China Hospital of Sichuan University

Chengdu, China

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Xuzhou Central Hospital

Xuzhou, China

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Yichang Central People's Hospital

Yichang, China

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Zhongshan City People's Hospital

Guangdong, China

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Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

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The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

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Evex Hospitals - Caucasus Medical Center

Tbilisi, 186, Georgia

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JSV VIAN- Caraps Medline

Tbilisi, 159, Georgia

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LLC Todua Clinic

Tbilisi, 112, Georgia

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Ltd "New Hospitals"

Tbilisi, 114, Georgia

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Tbilisi State Medical University and Ingorovka High Medical Technology University Clinic Ltd

Tbilisi, 114, Georgia

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Hiroshima City Hiroshima Citizens Hospital

Hiroshima, Japan

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Ishikawa Prefectural Central Hospital

Kanazawa, Japan

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Keiyukai Sapporo Hospital

Sapporo, Japan

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Osaki Citizen Hospital

Osaki-shi, Japan

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Saitama Cancer Center

Saitama, Japan

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Los Angeles Cancer Network

Anaheim, California, 92801, United States

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OPN - Oncology Physician Network (Los Alamitos)

Los Alamitos, California, 90720, United States

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Banner MD Anderson Cancer Center

Greeley, Colorado, 80631, United States

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Advanced Research LLC

Deerfield Beach, Florida, 33064, United States

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BRCR Medical Center

Plantation, Florida, 33322, United States

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Florida Cancer Specialist - East

West Palm Beach, Florida, 33401, United States

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Florida Cancer Specialist - North

St. Petersburg, Florida, 33705, United States

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Florida Cancer Specialist - South

Fort Myers, Florida, 33901, United States

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Napa Research

Pompano Beach, Florida, 33064, United States

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Northwestern University

Chicago, Illinois, 60611, United States

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Holden Comprehensive Cancer Center - University of Iowa

Iowa City, Iowa, 52242, United States

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Mission Cancer + Blood (Exigent Network)

Des Moines, Iowa, 50309, United States

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Washington University School of Medicine St. Louis

St Louis, Missouri, 63110, United States

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Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

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Comprehensive Cancer Centers Nevada

Las Vegas, Nevada, 89169, United States

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Cleveland Clinic

Cleveland, Ohio, 44195, United States

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Guthrie Medical Group, PC and Robert Packer Hospital (Guthrie Cancer Center - Sayre)

Sayre, Pennsylvania, 18840, United States

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UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

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Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

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Texas Oncology - Gulf Coast (SCRI)

Webster, Texas, 77598, United States

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Texas Oncology - West (SCRI)

Abilene, Texas, 79606, United States

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Texas Oncology Central South (SCRI)

Austin, Texas, 78705, United States

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The University of Texas MD Anderson cancer Center

Houston, Texas, 77030, United States

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American Oncology Network Vista Oncology Division

Olympia, Washington, 98502, United States

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Northwest Medical Specialties

Tacoma, Washington, 98405, United States

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West Virginia University Cancer Institute

Morgantown, West Virginia, 26506, United States

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Status: Recruiting

Trial Details

Show Summary from Sponsor

More details:

Investigational Drug AI Analysis

Show for: HLX22 (AC101)

Overview

Mechanism of action

Efficacy

Safety

Further reading

HealthScout AI Analysis

Eligibility

Show Criteria

Sites (88)

Concord Repatriation General Hospital

Peninsula Health-Frankston hospital

St. Vincent Hospital Melbourne

University of the Sunshine Coast Clinical Trials, Sunshine Coast Haematology and Oncology Clinic

Central Coast Local Health District (Gosford and Wyong Hospital)

GenesisCare Research

Macquarie University

Centro de Oncologia de Precision

Instituto del Cancer RedSalud Vitacura

Affiliated Hospital of Youjiang Medical University for Nationalities

Cancer Hospital Affiliated to Xinjiang Medical University

Cancer Hospital Chinese Academy of Medical Sciences

Cancer Hospital of Shandong First Medical University

Fujian Cancer Hospital

Gansu Provincial Cancer Hospital

Gansu Provincial Hospital

General Hospital of Ningxia Medical University

Harbin Medical University Cancer Hospital

Henan Cancer Hospital

Heping Hospital Affiliated to Changzhi Medical College

Hunan Cancer Hospital

Liaoning Medical University Cancer Institute & Hospital

Liuzhou Workers' Hospital

Mianyang Central Hospital

Nanjing Drum Tower Hospital

Peking Union Medical College Hospital

Qinghai University Affiliated Hospital

Renji Hospital,Shanghai Jiao Tong University School of Medicine

Shanxi Cancer Hospital

Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital

Sir Run Run Shaw Hospital (SRRSH), affiliated with the Zhejiang University School of Medicine

The Affiliated Hospital of Qingdao University

The Central Hospital of Shaoyang

The First Affiliated Hospital of Anhui Medical University

The First Affiliated Hospital of Bengbu Medical University

The First Affiliated Hospital of Chongqing Medical University

The First Affiliated Hospital of Henan University of Science

The First Affiliated Hospital of Nanchang University

The First Affiliated Hospital of Xiamen University

The First Affiliated Hospital of Zhengzhou University

The First Affiliated Hospital, Zhejiang University School of Medic

The First Hospital Of Lanzhou University

The First Hospital of Jilin University

The Second Hospital of Anhui Medical University

The Sixth Affiliated Hospital of Sun Yat-sen University

Tianjin Medical University Cancer Institute & Hospital

West China Hospital of Sichuan University

Xuzhou Central Hospital

Yichang Central People's Hospital

Zhongshan City People's Hospital

Beijing Cancer Hospital

The Fourth Hospital of Hebei Medical University

Evex Hospitals - Caucasus Medical Center

JSV VIAN- Caraps Medline

LLC Todua Clinic

Ltd "New Hospitals"

Tbilisi State Medical University and Ingorovka High Medical Technology University Clinic Ltd

Hiroshima City Hiroshima Citizens Hospital

Ishikawa Prefectural Central Hospital

Keiyukai Sapporo Hospital

Osaki Citizen Hospital

Saitama Cancer Center

Los Angeles Cancer Network

OPN - Oncology Physician Network (Los Alamitos)

Banner MD Anderson Cancer Center

Advanced Research LLC