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 a humanized IgG1 monoclonal antibody targeting HER2, originally discovered via an Alligator Bioscience–AbClon collaboration and sublicensed to Shanghai Henlius for clinical development. It is being studied primarily in HER2‑positive gastric/gastroesophageal junction (G/GEJ) adenocarcinoma in combination with trastuzumab and chemotherapy. In 2025, HLX22 received orphan drug designation for gastric cancer from both the U.S. FDA (March 19–20, 2025) and the European Commission (May 22–26, 2025). A global phase 3 trial (NCT06532006; HLX22‑GC‑301) is recruiting. (pubmed.ncbi.nlm.nih.gov, henlius.com, ema.europa.eu, cdek.pharmacy.purdue.edu)

Mechanism of action

HLX22 binds a non‑overlapping epitope in the HER2 extracellular domain IV, distinct from trastuzumab, enabling simultaneous binding with trastuzumab. Dual targeting increases internalization of HER2 homodimers and HER2/EGFR heterodimers by approximately 40–80%, reduces downstream signaling (e.g., STAT3, p70S6, AKT), and leads to synergistic antitumor activity in HER2‑positive gastric cancer models. (pmc.ncbi.nlm.nih.gov, translational-medicine.biomedcentral.com)

Efficacy

Phase 2 randomized, double‑blind study (NCT04908813) in untreated HER2‑positive locally advanced/metastatic G/GEJ cancer compared HLX22 (15 or 25 mg/kg) + trastuzumab biosimilar (HLX02) + XELOX vs placebo + HLX02 + XELOX. With 14.3 months median follow‑up (n=53), independent review committee–assessed median PFS improved:
25 mg/kg: 15.1 vs 8.2 months (HR 0.50; 95% CI 0.17–1.27)
15 mg/kg: not reached vs 8.2 months (HR 0.10; 95% CI 0.04–0.52) Confirmed ORR was similar across arms (77.8%/82.4% vs 88.9%). Duration of response favored HLX22. These results were presented at ASCO GI 2024 and published subsequently. (ascopubs.org, pubmed.ncbi.nlm.nih.gov)
An updated ASCO GI 2025 company summary (62 randomized; median follow‑up ~20–24 months) reported continued survival benefit with the HLX22 regimen; full peer‑reviewed details are pending. (henlius.com)
Phase 3 (NCT06532006; HLX22‑GC‑301): double‑blind, multicenter, 1:1 randomization to HLX22 (15 mg/kg) + trastuzumab + XELOX versus placebo + trastuzumab + XELOX, with optional pembrolizumab per protocol; primary endpoints are IRRC‑assessed PFS and OS. Sites include the U.S., EU, Japan, Australia; status recruiting in 2025. (cdek.pharmacy.purdue.edu, genesiscare.com, mdanderson.org)

Safety

Phase 1 (first‑in‑human, n=11): HLX22 up to 25 mg/kg Q3W was well tolerated; no dose‑limiting toxicities or serious AEs during treatment; most common TEAEs were lymphocyte count decreased (45.5%), WBC decreased (36.4%), and hypokalemia (36.4%). No objective responses; disease control rate 36.4%. (pubmed.ncbi.nlm.nih.gov)
Phase 2: Treatment‑related adverse events occurred in 100%, 94.1%, and 94.4% of patients in the 25 mg/kg, 15 mg/kg, and control arms, respectively; one grade 5 TRAE occurred in the control arm. Reported hematologic toxicities were consistent with the XELOX backbone; overall safety was described as manageable. (ascopubs.org, 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 in the first-line treatment of HER2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

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

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 and may be open-label while maintaining the HLX22 blind.

Treatments: Experimental: HLX22 15 mg/kg Q3W plus trastuzumab and XELOX, with optional placebo for pembrolizumab to maintain blinding. Control: placebo for HLX22 plus trastuzumab and XELOX, with optional pembrolizumab, Q3W. XELOX consists of oxaliplatin plus capecitabine, a standard first-line chemotherapy backbone for HER2-positive G/GEJ cancer when combined with trastuzumab. HLX22 is a humanized IgG1 anti‑HER2 monoclonal antibody that binds a domain IV epitope non‑overlapping with trastuzumab, enabling dual engagement and enhanced HER2 internalization and signaling inhibition. In a randomized phase 2 study in first-line HER2-positive G/GEJ cancer, HLX22 plus trastuzumab biosimilar and XELOX improved PFS versus placebo plus trastuzumab biosimilar and XELOX, with manageable safety aligned with the chemotherapy backbone. Early-phase data showed tolerability up to 25 mg/kg Q3W without dose-limiting toxicities.

Outcomes: Co-primary endpoints: IRRC-assessed progression-free survival per RECIST v1.1 and overall survival. Key secondary endpoints include investigator-assessed PFS, objective response rate by IRRC and investigator per RECIST v1.1, and safety/tolerability including adverse events.

Burden on patient: Moderate. The regimen uses standard Q3W IV infusions for trastuzumab, oxaliplatin, and study drug/placebo, plus oral capecitabine, mirroring standard first-line care. Additional burden arises from double-blind investigational infusions and more frequent imaging and safety labs typical of phase 3 studies over a prolonged follow-up period (up to 5 years). No intensive pharmacokinetic sampling or mandatory research biopsies are specified, and cardiac monitoring for anti‑HER2 therapy (e.g., periodic echocardiograms) aligns with standard practice. Travel frequency is similar to standard XELOX/trastuzumab schedules, with occasional extra visits for assessments, resulting in a moderate overall burden.

Eligibility

Show Criteria

Sites (88)

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St. Vincent Hospital Melbourne

Fitzroy, Melbourne, 3065, Australia

No email / No phone

Status: Recruiting

Peninsula Health-Frankston hospital

Frankston, Melbourne, 3940, Australia

No email / No phone

Status: Recruiting

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

Sunshine Coast, Queensland, 4556, Australia

No email / No phone

Status: Recruiting

Macquarie University

North Ryde, Sydney, 2109, Australia

No email / No phone

Status: Recruiting

GenesisCare Research

Campbelltown, Sydney, 2560, Australia

No email / No phone

Status: Recruiting

Central Coast Local Health District (Gosford and Wyong Hospital)

Gosford, Sydney, 2250, Australia

No email / No phone

Status: Recruiting

Concord Repatriation General Hospital

Concord, Sydney, Australia

No email / No phone

Status: Recruiting

Centro de Oncologia de Precision

Santiago, Santiago Metropolitan, 7560908, Chile

No email / No phone

Status: Recruiting

Instituto del Cancer RedSalud Vitacura

Santiago, Santiago Metropolitan, 7630000, Chile

No email / No phone

Status: Recruiting

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

No email / No phone

Status: Recruiting

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

No email / No phone

Status: Recruiting

Renji Hospital,Shanghai Jiao Tong University School of Medicine

Shanghai, China

No email / No phone

Status: Recruiting

The First Hospital of Jilin University

Changchun, China

No email / No phone

Status: Recruiting

Hunan Cancer Hospital

Changsha, China

No email / No phone

Status: Recruiting

Heping Hospital Affiliated to Changzhi Medical College

Changzhi, China

No email / No phone

Status: Recruiting

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

Chengdu, China

No email / No phone

Status: Recruiting

West China Hospital of Sichuan University

Chengdu, China

No email / No phone

Status: Recruiting

The First Affiliated Hospital of Chongqing Medical University

Chongqing, China

No email / No phone

Status: Recruiting

Fujian Cancer Hospital

Fuzhou, China

No email / No phone

Status: Recruiting

Zhongshan City People's Hospital

Guangdong, China

No email / No phone

Status: Recruiting

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, China

No email / No phone

Status: Recruiting

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

Hangzhou, China

No email / No phone

Status: Recruiting

The First Affiliated Hospital, Zhejiang University School of Medic

Hangzhou, China

No email / No phone

Status: Recruiting

Harbin Medical University Cancer Hospital

Harbin, China

No email / No phone

Status: Recruiting

The First Affiliated Hospital of Anhui Medical University

Hefei, China

No email / No phone

Status: Recruiting

The Second Hospital of Anhui Medical University

Hefei, China

No email / No phone

Status: Recruiting

Cancer Hospital of Shandong First Medical University

Jinan, China

No email / No phone

Status: Recruiting

Gansu Provincial Cancer Hospital

Lanzhou, China

No email / No phone

Status: Recruiting

Gansu Provincial Hospital

Lanzhou, China

No email / No phone

Status: Recruiting

The First Hospital Of Lanzhou University

Lanzhou, China

No email / No phone

Status: Recruiting

Liuzhou Workers' Hospital

Liuzhou, China

No email / No phone

Status: Recruiting

The First Affiliated Hospital of Henan University of Science

Luoyang, China

No email / No phone

Status: Recruiting

Mianyang Central Hospital

Mianyang, China

No email / No phone

Status: Recruiting

The First Affiliated Hospital of Nanchang University

Nanchang, China

No email / No phone

Status: Recruiting

Nanjing Drum Tower Hospital

Nanjing, China

No email / No phone

Status: Recruiting

The Affiliated Hospital of Qingdao University

Qingdao, China

No email / No phone

Status: Recruiting

The Central Hospital of Shaoyang

Shaoyang, China

No email / No phone

Status: Recruiting

Liaoning Medical University Cancer Institute & Hospital

Shenyang, China

No email / No phone

Status: Recruiting

Shanxi Cancer Hospital

Taiyuan, China

No email / No phone

Status: Recruiting

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

No email / No phone

Status: Recruiting

Cancer Hospital Affiliated to Xinjiang Medical University

Ürümqi, China

No email / No phone

Status: Recruiting

The First Affiliated Hospital of Xiamen University

Xiamen, China

No email / No phone

Status: Recruiting

Qinghai University Affiliated Hospital

Xining, China

No email / No phone

Status: Recruiting

Xuzhou Central Hospital

Xuzhou, China

No email / No phone

Status: Recruiting

Yichang Central People's Hospital

Yichang, China

No email / No phone

Status: Recruiting

General Hospital of Ningxia Medical University

Yinchuan, China

No email / No phone

Status: Recruiting

Henan Cancer Hospital

Zhengzhou, China

No email / No phone

Status: Recruiting

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

No email / No phone

Status: Recruiting

Affiliated Hospital of Youjiang Medical University for Nationalities

Baise City, China

No email / No phone

Status: Recruiting

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

No email / No phone

Status: Recruiting

Peking Union Medical College Hospital

Beijing, China

No email / No phone

Status: Recruiting

The First Affiliated Hospital of Bengbu Medical University

Bengbu, China

No email / No phone

Status: Recruiting

Evex Hospitals - Caucasus Medical Center

Tbilisi, 186, Georgia

No email / No phone

Status: Recruiting

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

Tbilisi, 114, Georgia

No email / No phone

Status: Recruiting

LLC Todua Clinic

Tbilisi, 112, Georgia

No email / No phone

Status: Recruiting

Ltd "New Hospitals"

Tbilisi, 114, Georgia

No email / No phone

Status: Recruiting

JSV VIAN- Caraps Medline

Tbilisi, 159, Georgia

No email / No phone

Status: Recruiting

Hiroshima City Hiroshima Citizens Hospital

Hiroshima, Japan

No email / No phone

Status: Recruiting

Osaki Citizen Hospital

Osaki-shi, Japan

No email / No phone

Status: Recruiting

Ishikawa Prefectural Central Hospital

Kanazawa, Japan

No email / No phone

Status: Recruiting

Keiyukai Sapporo Hospital

Sapporo, Japan

No email / No phone

Status: Recruiting

Saitama Cancer Center

Saitama, Japan

No email / No phone

Status: Recruiting

OPN - Oncology Physician Network (Los Alamitos)

Los Alamitos, California, 90720, United States

No email / No phone

Status: Recruiting

Los Angeles Cancer Network

Anaheim, California, 92801, United States

No email / No phone

Status: Recruiting

Banner MD Anderson Cancer Center

Greeley, Colorado, 80631, United States

No email / No phone

Status: Recruiting

Florida Cancer Specialist - North

St. Petersburg, Florida, 33705, United States

No email / No phone

Status: Recruiting

Florida Cancer Specialist - East

West Palm Beach, Florida, 33401, United States

No email / No phone

Status: Recruiting

Napa Research

Pompano Beach, Florida, 33064, United States

No email / No phone

Status: Recruiting

BRCR Medical Center

Plantation, Florida, 33322, United States

No email / No phone

Status: Recruiting

Florida Cancer Specialist - South

Fort Myers, Florida, 33901, United States

No email / No phone

Status: Recruiting

Advanced Research LLC

Deerfield Beach, Florida, 33064, United States

No email / No phone

Status: Recruiting

Northwestern University

Chicago, Illinois, 60611, United States

No email / No phone

Status: Recruiting

Mission Cancer + Blood (Exigent Network)

Des Moines, Iowa, 50309, United States

No email / No phone

Status: Recruiting

Holden Comprehensive Cancer Center - University of Iowa

Iowa City, Iowa, 52242, United States

No email / No phone

Status: Recruiting

Washington University School of Medicine St. Louis

St Louis, Missouri, 63110, United States

No email / No phone

Status: Recruiting

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

No email / No phone

Status: Recruiting

Comprehensive Cancer Centers Nevada

Las Vegas, Nevada, 89169, United States

No email / No phone

Status: Recruiting

Cleveland Clinic

Cleveland, Ohio, 44195, United States

No email / No phone

Status: Recruiting

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

No email / No phone

Status: Recruiting

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

Sayre, Pennsylvania, 18840, United States

No email / No phone

Status: Recruiting

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

No email / No phone

Status: Recruiting

Texas Oncology - West (SCRI)

Abilene, Texas, 79606, United States

No email / No phone

Status: Recruiting

Texas Oncology - Gulf Coast (SCRI)

Webster, Texas, 77598, United States

No email / No phone

Status: Recruiting

Texas Oncology Central South (SCRI)

Austin, Texas, 78705, United States

No email / No phone

Status: Recruiting

The University of Texas MD Anderson cancer Center

Houston, Texas, 77030, United States

No email / No phone

Status: Recruiting

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

No email / No phone

Status: Recruiting

American Oncology Network Vista Oncology Division

Olympia, Washington, 98502, United States

No email / No phone

Status: Recruiting

West Virginia University Cancer Institute

Morgantown, West Virginia, 26506, United States

No email / No phone

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)

St. Vincent Hospital Melbourne

Peninsula Health-Frankston hospital

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

Macquarie University

GenesisCare Research

Central Coast Local Health District (Gosford and Wyong Hospital)

Concord Repatriation General Hospital

Centro de Oncologia de Precision

Instituto del Cancer RedSalud Vitacura

Beijing Cancer Hospital

The Fourth Hospital of Hebei Medical University

Renji Hospital,Shanghai Jiao Tong University School of Medicine

The First Hospital of Jilin University

Hunan Cancer Hospital

Heping Hospital Affiliated to Changzhi Medical College

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

West China Hospital of Sichuan University

The First Affiliated Hospital of Chongqing Medical University

Fujian Cancer Hospital

Zhongshan City People's Hospital

The Sixth Affiliated Hospital of Sun Yat-sen University

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

The First Affiliated Hospital, Zhejiang University School of Medic

Harbin Medical University Cancer Hospital

The First Affiliated Hospital of Anhui Medical University

The Second Hospital of Anhui Medical University

Cancer Hospital of Shandong First Medical University

Gansu Provincial Cancer Hospital

Gansu Provincial Hospital

The First Hospital Of Lanzhou University

Liuzhou Workers' Hospital

The First Affiliated Hospital of Henan University of Science

Mianyang Central Hospital

The First Affiliated Hospital of Nanchang University

Nanjing Drum Tower Hospital

The Affiliated Hospital of Qingdao University

The Central Hospital of Shaoyang

Liaoning Medical University Cancer Institute & Hospital

Shanxi Cancer Hospital

Tianjin Medical University Cancer Institute & Hospital

Cancer Hospital Affiliated to Xinjiang Medical University

The First Affiliated Hospital of Xiamen University

Qinghai University Affiliated Hospital

Xuzhou Central Hospital

Yichang Central People's Hospital

General Hospital of Ningxia Medical University

Henan Cancer Hospital

The First Affiliated Hospital of Zhengzhou University

Affiliated Hospital of Youjiang Medical University for Nationalities

Cancer Hospital Chinese Academy of Medical Sciences

Peking Union Medical College Hospital

The First Affiliated Hospital of Bengbu Medical University

Evex Hospitals - Caucasus Medical Center

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

LLC Todua Clinic

Ltd "New Hospitals"

JSV VIAN- Caraps Medline

Hiroshima City Hiroshima Citizens Hospital

Osaki Citizen Hospital

Ishikawa Prefectural Central Hospital

Keiyukai Sapporo Hospital

Saitama Cancer Center

OPN - Oncology Physician Network (Los Alamitos)

Los Angeles Cancer Network

Banner MD Anderson Cancer Center

Florida Cancer Specialist - North