A Randomized, Double-blinded, Multicenter, Phase Ⅲ Clinical Study of HLX22 (Recombinant Humanized Anti-HER2 Monoclonal Antibody Injection) in Combination with Trastuzumab and Chemotherapy (XELOX) versus Trastuzumab and Chemotherapy (XELOX) with or without Pembrolizumab for the First Line Treatment of Locally Advanced or Metastatic Gastroesophageal Junction and Gastric Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Shanghai Henlius Biotech Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Jun 2025 → ongoing

Decision date (initial)

2025-04-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Shanghai Henlius Biotech, Inc.

External identifiers

EU CT number

2024-516633-12-00

ClinicalTrials.gov

NCT06532006

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Efficacy, Safety, Others

To evaluate the efficacy of HLX22 in combination with trastuzumab + chemotherapy versus trastuzumab + chemotherapy ± pembrolizumab as first-line treatment for patients with locally advanced/metastatic gastroesophageal junction and gastric cancer.

Secondary objectives 2

1. To evaluate the safety of HLX22 in combination with trastuzumab + chemotherapy versus trastuzumab + chemotherapy ± pembrolizumab as first-line treatment for patients with locally advanced/metastatic gastroesophageal junction and gastric cancer.
2. To study the pharmacokinetic (PK) characteristics of HLX22.

Conditions and MedDRA coding

Locally advanced/ metastatic gastroesophageal junction and gastric cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

The plan to share Individual Participant Data (IPD) is currently pending, as it requires further ethical approvals and consent from investigators and patients.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Voluntary participation in the clinical study; fully understands and is informed of the study and has signed the ICF; willing to comply with and able to complete all trial procedures.
2. Male or female who is at least 18 years of age or a country’s minimal age of maturity or greater on the day of signing the informed consent.
3. With histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma.
4. Has measurable disease as assessed by BICR according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, the target lesion must not be a bone metastatic lesion only.
5. 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.
6. ECOG PS within 7 days before randomization: 0-1.
7. Expected survival ≥ 6 months.
8. Hepatitis B surface antigen (HBsAg) (–) and hepatitis B core antibody (HBcAb) (–); if HBsAg (+) or HBcAb (+), hepatitis B virus deoxyribonucleic acid (HBV-DNA) must be < 2,500 copies/mL or 500 IU/mL or within the normal range of this site (And if the site has a normal range, HBV-DNA should be within the range of the site).
9. HCV antibody (–); if HCV antibody (+), HCV-RNA testing must be negative before enrollment. Subjects co-infected with hepatitis B and C will be excluded (tested positive for HBsAg or HBcAb and positive for HCV antibody).
10. HIV antibody (–); if HIV antibody (+), the subject should receive antiretroviral therapy for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
11. Has adequate organ function as defined in the protocol.
12. Female subjects of childbearing potential must have a negative blood pregnancy test within 7 days before randomization. Female subjects of childbearing potential and male subjects with female partners of childbearing potential have to adopt at least one highly effective contraceptive measure as defined by Clinical Trials Facilitation Group（CTFG） (such as intra-uterine contraceptive device, contraceptive pill or condom, female/male sterilization, etc.) during the study treatment period, and at least 9 months after the last dose of study treatment.

Exclusion criteria 19

1. Subjects with other malignant tumors within 2 years before the randomization. Subjects with localized tumors that have been resolved, such as cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, and thyroid carcinoma, may be enrolled.
2. Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma.. Patient may have received prior perioperative therapy (neoadjuvant or adjuvant therapy) as long as it was completed at least 6 months prior to randomization and without progression.
3. Prior use of doxorubicin with in vivo concentrations > 360 mg/m2 (or equivalent) as described in the protocol.
4. Previous treatment with any HER2-target therapy.
5. Residual toxicity resulting from previous therapy. Alopecia is permitted.
6. Active gastrointestinal bleeding (Grade ≥ 2 according to National Cancer Institute [NCI] CTCAE v5.0).
7. Presence of central nervous system (CNS) metastases and/or leptomeningeal disease.
8. Occurrence of cerebrovascular accidents, myocardial infarction, unstable angina and poorly controlled arrhythmia (including QTc interval ≥ 470 ms) (QTc interval calculated according to the Fridericia formula) within half a year prior to the randomization.
9. According to the New York Heart Association (NYHA) classification, subjects with class III or IV cardiac insufficiency or color Doppler echocardiogram (ECHO): left ventricular ejection fraction (LVEF) < 55%.
10. Subjects with history or complicated interstitial lung disease, an active infection requiring systemic therapy or active tuberculosis.
11. Subjects who received live vaccines within 28 days prior to randomization; except for seasonal influenza or inactivated COVID-19 vaccines.
12. Subjects who had a major surgery within 28 days prior to the randomization.
13. Subjects who received radical radiotherapy within 28 days prior to the randomization.
14. Subjects who were participating in or had participated in a study of an investigational agent or had used an investigational device within 28 days prior to the randomization.
15. Subjects who had known history of severe allergy to any monoclonal antibody or any component of study treatment.
16. Subjects who had a known history of psychotropic drug abuse or drug addiction.
17. Lactating subject.
18. Known dihydropyrimidine dehydrogenase deficiency or current use of antiviral drug sorivudine or its chemically related analogs, such as brivudine.
19. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression-free survival (PFS) (assessed by the Blinded Independent Central Review [BICR] per RECIST v1.1).
2. Overall survival (OS).

Secondary endpoints 8

1. Progression-free survival (PFS) (assessed by investigator per RECIST v1.1).
2. Objective response rate (ORR) (assessed by BICR and investigator per RECIST v1.1).
3. Progression-free survival on next line of therapy (PFS2) (assessed by investigator per RECIST v1.1)
4. Duration of response (DOR) (assessed by BICR and investigator per RECIST v1.1).
5. Incidence of adverse events (AEs) and serious adverse events (SAEs).
6. PK: concentration of HLX22 in serum.
7. Immunogenicity evaluation: incidence of anti-drug antibody (ADA) and neutralizing antibody (NAb) of HLX22.
8. Quality of life assessment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Shanghai Henlius Biotech Inc.

Sponsor organisation

Shanghai Henlius Biotech Inc.

Address

Room 330 Complex Building, No 222 Kangnan Road, Shanghai Pilot Free Trade Zone No 222 Kangnan Road Shanghai Pilot Free Trade Zone

City

Shanghai

Postcode

201203

Country

China

Scientific contact point

Organisation

Shanghai Henlius Biotech Inc.

Contact name

Clinical Development

Public contact point

Organisation

Shanghai Henlius Biotech Inc.

Contact name

Clinical Development

Third parties 9

Locations

7 EU/EEA countries · 53 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 121 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications