Sponsor: Shanghai Henlius Biotech (industry)
Phase: 3
Start date: Nov. 22, 2024
Planned enrollment: 550
HLX22 (AC101) is an investigational antibody targeting HER2. It is being studied with trastuzumab and chemotherapy for HER2-positive advanced gastric or gastroesophageal-junction cancer. A phase 3 trial is underway; the efficacy results below come from smaller phase 1 and phase 2 studies. (alligatorbioscience.se)
HLX22 binds a site on HER2 that does not overlap with trastuzumab’s binding site. In laboratory and animal studies, the two antibodies together increased internalization of HER2-containing receptor complexes and reduced growth-related signaling. Whether those findings fully explain the effects observed in patients remains uncertain. (pubmed.ncbi.nlm.nih.gov)
In an updated, randomized phase 2 analysis, 31 patients received HLX22 plus trastuzumab and capecitabine/oxaliplatin (XELOX), while 31 received placebo plus trastuzumab and XELOX. Confirmed objective response rates were 87.1% and 80.6%, respectively. Median progression-free survival had not been reached in the HLX22 group, versus 8.3 months in the control group (hazard ratio 0.20; 95% confidence interval 0.09–0.54). Median overall survival had not been reached versus 16.4 months, but the overall-survival estimate remained uncertain. These are promising phase 2 findings, not confirmation of benefit in a phase 3 trial. (ascopubs.org)
In an earlier phase 1 study of HLX22 alone in 11 previously treated patients with HER2-overexpressing solid tumors, no complete or partial responses occurred; four patients (36.4%) had stable disease. (pubmed.ncbi.nlm.nih.gov)
In the updated phase 2 analysis, grade 3 or higher treatment-emergent adverse events occurred in 54.8% of the HLX22 group and 48.4% of the control group. One placebo-group patient had an HLX22- or placebo-related adverse event leading to death; none were reported in the HLX22 group. In the phase 1 monotherapy study, there were no serious adverse events or dose-limiting toxicities during treatment, although the study included only 11 patients. (ascopubs.org)
Last updated: Sep 2026
Goal: Determine whether adding HLX22 to first-line trastuzumab and XELOX improves outcomes in HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma.
Patients: Adults with previously untreated, unresectable locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma, measurable disease, and ECOG performance status 0–1. Patients with prior HER2-targeted therapy, CNS metastases, active gastrointestinal bleeding, or LVEF below 55% are excluded.
Design: Multicenter, double-blind phase 3 trial with 1:1 randomization. Treatment continues until loss of clinical benefit, death, unacceptable toxicity, consent withdrawal, or another protocol-defined reason.
Treatments: The experimental arm receives HLX22 15 mg/kg with trastuzumab and XELOX every 3 weeks, with or without placebo for pembrolizumab. The control arm receives placebo for HLX22 with trastuzumab and XELOX every 3 weeks, with or without pembrolizumab. HLX22 is an investigational anti-HER2 antibody that binds a site distinct from trastuzumab’s; preclinical work suggests the combination increases HER2 receptor internalization and reduces growth signaling. In a smaller randomized phase 2 study, median progression-free survival was not reached with HLX22 versus 8.3 months with placebo, but phase 3 benefit remains unconfirmed.
Outcomes: Primary endpoints are independent radiology-reviewed progression-free survival by RECIST 1.1 and overall survival. Secondary endpoints include investigator-assessed progression-free survival, objective response rate assessed by independent review and investigators, and adverse events. Follow-up for these outcomes is up to 5 years.
Burden on patient: Moderate: treatment requires visits every 3 weeks for antibody therapy and oxaliplatin, alongside oral capecitabine, plus periodic imaging and safety assessments. These visits largely resemble first-line combination-treatment care, but study monitoring may add appointments or tests; the supplied information does not specify mandatory research biopsies or intensive pharmacokinetic sampling.
Last updated: Sep 2026
Inclusion Criteria:
1. Male/female who are at least 18 years of age on the day of signing the informed consent.
2. With histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma.
3. Had measurable disease as assessed by IRRC according to the RECIST v1.1, the target lesion must not be a bone metastatic lesion only.
4. HER2-positive tumor defined as either IHC 3+ or IHC 2+ in combination with ISH+ or FISH, as assessed by a central laboratory on a primary or metastatic tumor.
5. ECOG PS within 7 days before randomization: 0-1.
6. Expected survival ≥ 6 months.
7. Had adequate organ function
Exclusion Criteria:
1. Patients with other malignant tumors within 2 years before the randomization.
2. Evidence of disease progression within 6 months (before randomization) after completion of prior neoadjuvant or adjuvant chemotherapy (or both) or radiotherapy for gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
3. Previous treatment with any HER2-target therapy.
4. Active gastrointestinal bleeding
5. Presence of central nervous system (CNS) metastases.
6. Left ventricular ejection fraction (LVEF) \< 55%.
7. Subjects who had known history of severe allergy to any monoclonal antibody or any component of study treatment.
Concord, Sydney, Australia
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Frankston, Melbourne, 3940, Australia
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Fitzroy, Melbourne, 3065, Australia
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Sunshine Coast, Queensland, 4556, Australia
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Gosford, Sydney, 2250, Australia
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Campbelltown, Sydney, 2560, Australia
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North Ryde, Sydney, 2109, Australia
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Santiago, Santiago Metropolitan, 7560908, Chile
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Santiago, Santiago Metropolitan, 7630000, Chile
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Baise City, China
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Ürümqi, China
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Beijing, China
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Jinan, China
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Fuzhou, China
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Lanzhou, China
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Lanzhou, China
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Yinchuan, China
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Harbin, China
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Zhengzhou, China
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Changzhi, China
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Changsha, China
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Shenyang, China
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Liuchow, China
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Mianyang, China
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Nanjing, China
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Beijing, China
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Xining, China
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Shanghai, China
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Taiyuan, China
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Chengdu, China
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Hangzhou, China
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Qingdao, China
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Shaoyang, China
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Hefei, China
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Bengbu, China
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Chongqing, China
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Luoyang, China
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Nanchang, China
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Xiamen, China
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Zhengzhou, China
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Hangzhou, China
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Lanzhou, China
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Changchun, China
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Hefei, China
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Guangzhou, China
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Tianjin, China
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Chengdu, China
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Xuzhou, China
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Yichang, China
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Guangdong, China
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Beijing, Beijing Municipality, 100142, China
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Shijiazhuang, Hebei, China
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Tbilisi, 186, Georgia
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Tbilisi, 159, Georgia
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Tbilisi, 112, Georgia
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Tbilisi, 114, Georgia
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Tbilisi, 114, Georgia
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Hiroshima, Japan
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Kanazawa, Japan
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Sapporo, Japan
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Osaki-shi, Japan
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Saitama, Japan
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Anaheim, California, 92801, United States
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Los Alamitos, California, 90720, United States
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Greeley, Colorado, 80631, United States
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Deerfield Beach, Florida, 33064, United States
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Plantation, Florida, 33322, United States
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West Palm Beach, Florida, 33401, United States
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St. Petersburg, Florida, 33705, United States
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Fort Myers, Florida, 33901, United States
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Pompano Beach, Florida, 33064, United States
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Chicago, Illinois, 60611, United States
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Iowa City, Iowa, 52242, United States
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Des Moines, Iowa, 50309, United States
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St Louis, Missouri, 63110, United States
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Omaha, Nebraska, 68130, United States
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Las Vegas, Nevada, 89169, United States
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Cleveland, Ohio, 44195, United States
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Sayre, Pennsylvania, 18840, United States
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Pittsburgh, Pennsylvania, 15232, United States
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Nashville, Tennessee, 37232, United States
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Webster, Texas, 77598, United States
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Abilene, Texas, 79606, United States
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Austin, Texas, 78705, United States
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Houston, Texas, 77030, United States
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Olympia, Washington, 98502, United States
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Tacoma, Washington, 98405, United States
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Morgantown, West Virginia, 26506, United States
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