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
- Conditions
- Locally advanced/ metastatic gastroesophageal junction and gastric cancer
- Interventions
- Registration Number
- 2024-516633-12-00
- Lead Sponsor
- Shanghai Henlius Biotech Inc.
- Brief Summary
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.
- Detailed Description
In experimental group: HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) ± placebo (for pembrolizumab), once every 3 weeks (Q3W).
In control group: Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) ± pembrolizumab, Q3W.
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 91
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.
HIV antibody (–); if HIV antibody (+), the subject should establish antiretroviral therapy for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
Has adequate organ function as defined in the protocol.
Female subjects of childbearing potential had to 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 had 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) during the study treatment period, and at least nine months after the last dose of study treatment.
Male/female who were at least 18 years of age on the day of signing the informed consent.
With histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma.
Had 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.
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.
ECOG PS within 7 days before randomization: 0-1.
Expected survival ≥ 6 months.
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.
HCV antibody (–); if HCV antibody (+), HCV-RNA testing must be negative before enrollment. Subjects co-infected with hepatitis B and C must be excluded (tested positive for HBsAg or HBcAb and positive for HCV antibody).
Patients with other malignant tumors within 2 years before the randomization. Patients 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, can be enrolled.
Known dihydropyrimidine dehydrogenase deficiency or current use of antiviral drug sorivudine or its chemically related analogs, such as brivudine.
Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer. Patient may have received prior neoadjuvant or adjuvant therapy as long as it was completed at least 6 months prior to randomization and there was no evidence of progression within the timeframe.
Prior use of doxorubicin with in vivo concentrations > 360 mg/m2 (or equivalent) as described in the protocol.
Previous treatment with any HER2-target therapy.
Residual toxicity resulting from previous therapy. Alopecia is permitted.
Active gastrointestinal bleeding (Grade ≥ 2 according to National Cancer Institute [NCI] CTCAE v5.0).
Presence of central nervous system (CNS) metastases and/or carcinomatous meningitis.
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
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%.
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.
Patients with an active infection requiring systemic therapy or active tuberculosis.
Patients who received treatment with live vaccines within 28 days prior to randomization; except for seasonal influenza or inactivated COVID-19 vaccines.
Patients who received major surgery within 28 days prior to the randomization.
Patients who received radical radiotherapy within 28 days prior to the randomization.
Patients 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.
Subjects who had known history of severe allergy to any monoclonal antibody or any component of study treatment.
Subjects who had a known history of psychotropic drug abuse or drug addiction.
Lactating patient.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental group HLX22 Experimental group: HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) ± placebo (for pembrolizumab), Q3W Subjects in the experimental group may use one of the treatments below: HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) or HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) + placebo (for pembrolizumab) Experimental group Trastuzumab Experimental group: HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) ± placebo (for pembrolizumab), Q3W Subjects in the experimental group may use one of the treatments below: HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) or HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) + placebo (for pembrolizumab) Experimental group Oxaliplatin Experimental group: HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) ± placebo (for pembrolizumab), Q3W Subjects in the experimental group may use one of the treatments below: HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) or HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) + placebo (for pembrolizumab) Experimental group Capecitabine Experimental group: HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) ± placebo (for pembrolizumab), Q3W Subjects in the experimental group may use one of the treatments below: HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) or HLX22 (15 mg/kg) + trastuzumab + chemotherapy (XELOX) + placebo (for pembrolizumab) Control group Pembrolizumab Control group: Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) ± pembrolizumab, Q3W Subjects in the control group may use one of the treatments below: Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) or Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) + pembrolizumab Control group Oxaliplatin Control group: Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) ± pembrolizumab, Q3W Subjects in the control group may use one of the treatments below: Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) or Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) + pembrolizumab Control group Capecitabine Control group: Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) ± pembrolizumab, Q3W Subjects in the control group may use one of the treatments below: Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) or Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) + pembrolizumab Control group Trastuzumab Control group: Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) ± pembrolizumab, Q3W Subjects in the control group may use one of the treatments below: Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) or Placebo (for HLX22) + trastuzumab + chemotherapy (XELOX) + pembrolizumab
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) (assessed by the Blinded Independent Central Review [BICR] per RECIST v1.1). Progression-free survival (PFS) (assessed by the Blinded Independent Central Review [BICR] per RECIST v1.1).
Overall survival (OS). Overall survival (OS).
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) (assessed by investigator per RECIST v1.1). Progression-free survival (PFS) (assessed by investigator per RECIST v1.1).
Objective response rate (ORR) (assessed by BICR and investigator per RECIST v1.1). Objective response rate (ORR) (assessed by BICR and investigator per RECIST v1.1).
Progression-free survival on next line of therapy (PFS2) (assessed by investigator per RECIST v1.1) Progression-free survival on next line of therapy (PFS2) (assessed by investigator per RECIST v1.1)
Duration of response (DOR) (assessed by BICR and investigator per RECIST v1.1). Duration of response (DOR) (assessed by BICR and investigator per RECIST v1.1).
Incidence of adverse events (AEs) and serious adverse events (SAEs). Incidence of adverse events (AEs) and serious adverse events (SAEs).
Pharmacokinetics (PK): concentration of HLX22 in serum. Pharmacokinetics (PK): concentration of HLX22 in serum.
Immunogenicity evaluation: incidence of anti-drug antibody (ADA) and neutralizing antibody (NAb) of HLX22. Immunogenicity evaluation: incidence of anti-drug antibody (ADA) and neutralizing antibody (NAb) of HLX22.
Quality of life assessment. Quality of life assessment.
Trial Locations
- Locations (42)
Technische Universitaet Dresden
🇩🇪Dresden, Germany
Universitaetsklinikum Jena KöR
🇩🇪Jena, Germany
Medizinische Hochschule Hannover
🇩🇪Hanover, Germany
Klinikum der Universitaet Muenchen AöR
🇩🇪Munich, Germany
SLK-Kliniken Heilbronn GmbH
🇩🇪Heilbronn, Germany
Klinikum St Marien Amberg
🇩🇪Amberg, Germany
Evangelisches Klinikum Bethel gGmbH
🇩🇪Bielefeld, Germany
Haematologisch-Onkologische Praxis Eppendorf (HOPE)
🇩🇪Hamburg, Germany
Kreiskliniken Reutlingen gGmbH
🇩🇪Reutlingen, Germany
Azienda Ospedaliero Universitaria Delle Marche
🇮🇹Ancona, Italy
Scroll for more (32 remaining)Technische Universitaet Dresden🇩🇪Dresden, GermanyGunnar FolprechtSite contact+493514584794gunnar.folprecht@uniklinikum-dresden.de