ASKB589 in Combination With CAPOX and PD-1 Inhibitor in Patients With Advanced or Metastatic GC/GEJ Adenocarcinoma

A Phase III Study Evaluating the Efficacy and Safety of ASKB589 Combined With CAPOX and PD-1 Inhibitor as First-Line Treatment in Claudin18.2 Positive Patients With Unresectable Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

This study is a multicenter, randomized, double-blind, standard-of-care controlled phase III clinical study conducted in China. The purpose of this study is to evaluate the efficacy of ASKB589 plus CAPOX and PD-1 inhibitor compared with placebo plus CAPOX and PD-1 inhibitor (as first-line treatment) as measured by Progression Free Survival (PFS).

Study Overview

• Status: Active, not recruiting
• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Capecitabine; Drug: ASKB589; Drug: Oxaliplatin; Drug: Tislelizumab; Drug: Placebo

Detailed Description

This study is a multicenter, randomized, double-blind, standard-of-care controlled phase III clinical study conducted in China. The purpose of this study is to evaluate the efficacy of ASKB589 plus CAPOX and PD-1 inhibitor compared with placebo plus CAPOX and PD-1 inhibitor (as first-line treatment) as measured by Progression Free Survival (PFS).

This study will also evaluate efficacy, physical function, safety, and tolerability of ASKB589, as well as its effects on quality of life. Pharmacokinetics (PK) of ASKB589 and the immunogenicity profile of ASKB589 will be evaluated as well.

• Study Type: Interventional
• Enrollment (Estimated): 780
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of gastric and gastroesophageal junction
2. Advanced recurrent or metastatic disease confirmed by imaging within 28 days prior to randomization
3. Suitable for chemotherapy combined with PD-1 inhibitor
4. Not suitable for anti-HER2 therapy
5. Have at least one measurable lesion according to RECIST1.1 assessed by site investigator within 28 days prior to randomization
6. CLDN 18.2 positive

Exclusion Criteria:

1. Patients with active central nervous system (CNS) metastases or suspected carcinomatous meningitis
2. Participants have significant gastric bleeding
3. The presence of clinically uncontrollable third interspace fluid
4. Received anti-CLDN18.2 antibody at any time in the past
5. Suspected complete or partial obstruction of gastroesophageal access

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Treatment with intravenous infusion of ASKB589 on day 1 of each cycle. The infusion duration should be at least 3 hours, and can be shortened or extended in subsequent cycles as appropriate according to the patient's tolerability. Interruption or slow down of intravenous infusion is allowed to manage toxicity. Dosing is continued every cycle until participants meet the criteria of treatment discontinuation.	Drug: Capecitabine; Capecitabine will be administered orally twice daily (bid).; Drug: ASKB589; ASKB589 will be administered as a minimum 3-hour IV infusion; Drug: Oxaliplatin; Oxaliplatin will be administered as a minimum 2-hour IV infusion; Drug: Tislelizumab; Tislelizumab will be administered every 3 weeks Intravenous infusion on day 1 of each cycle.
Placebo Comparator: Group B; Treatment with intravenous infusion of placebo on day 1 of each cycle. The infusion duration should be at least 3 hours, and can be shortened or extended in subsequent cycles as appropriate according to the patient's tolerability. Interruption or slow down of intravenous infusion is allowed to manage toxicity. Dosing is continued every cycle until participants meet the criteria for treatment discontinuation.	Drug: Capecitabine; Capecitabine will be administered orally twice daily (bid).; Drug: Oxaliplatin; Oxaliplatin will be administered as a minimum 2-hour IV infusion; Drug: Tislelizumab; Tislelizumab will be administered every 3 weeks Intravenous infusion on day 1 of each cycle.; Drug: Placebo; Placebo will be administered as a minimum 3-hour IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization until the date of radiological progressive disease (per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by Independent Review Committee (IRC)) or death from any cause, whichever is earliest.	Until disease progression or withdrawal from the study (generally up to 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the date of randomization until the date of death from any cause.	Until death or withdrawal from the study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by Independent Review Committee (IRC) per RECIST 1.1.	Until disease progression or withdrawal from the study (generally up to 24 months)
Duration Of Response (DOR)	DOR, defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by IRC per RECIST 1.1 or date of death from any cause, whichever is earliest.	Until disease progression or withdrawal from the study (generally up to 24 months)
Safety and tolerability assessed by adverse events (AEs)	An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Until 90 days after the end of treatment
Number of participants with laboratory assessments abnormalities	Number of participants with potentially clinically significant laboratory values.	Until the end of treatment (generally up to 24 months)
Number of participants with vital signs abnormalities and/or adverse events	Number of participants with potentially clinically significant vital sign values.	Until 90 days after the end of treatment
Health Related Quality of Life (HRQoL) measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC-QLQ-C30)	EORTC-QLQ-C30 is a cancer-specific 30-item questionnaire. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change	Until the end of treatment (generally up to 24 months)
Health Related Quality of Life (HRQoL) measured by the Global Pain (GP) questionnaire	The GP instrument is a single assessment of overall pain where 0 equals no pain and 10 equals extreme pain. Low pain scores are considered a better outcome than a high pain score	Until the end of treatment (generally up to 24 months)
Health Related Quality of Life (HRQoL) measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) questionnaire	The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.	Until the end of treatment (generally up to 24 months)
Pharmacokinetics (PK) of ASKB589	Ctrough will be derived from the PK serum samples collected.	up to 6 cycles (21 days for 1 cycle)
Number of anti-drug antibody (ADA) Positive Participants	Immunogenicity will be measured by the number of participants that are ADA positive.	up to 6 cycles (21 days for 1 cycle)

Collaborators and Investigators

• Sponsor: AskGene Pharma, Inc.
• Collaborators: Jiangsu Aosaikang Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: January 12, 2024
• First Posted (Actual): January 16, 2024

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; CLDN 18.2; ASKB589
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; tislelizumab
• Other Study ID Numbers: ASK-LC-B589-III-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No