ASKB589 in Combination With CAPOX and Sintilimab in Patients With Advanced, and Unresectable G/GEJ Cancer.

Study Overview
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Brief Summary
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This was an open-label, phase 1/2 study to evaluate safety, tolerability, pharmacokinetics, and antitumor activity of ASKB589 in combination with CAPOX and Sintilimab in first-line treatment of patients with locally advanced, recurrent, or metastatic gastric and esophagogastric junction adenocarcinoma.

Detailed Description
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A two-part, dose-escalation and expansion study of ASKB589 was initiated to determine the MTD, PK, PD, and efficacy in combination with chemotherapy and Sintilimab.

Official Title
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A 1/2 Phase Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ASKB589 in Combination With CAPOX and Sintilimab in Patients With Advanced, and Unresectable Gastric/Esophagogastric Junction Cancer.

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: ASKB589 +CAPOX+Sintilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically confirmed unresectable locally advanced, recurrent, or metastatic adenocarcinoma of the gastric and gastroesophageal junction currently ineligible for surgery and radical radiotherapy. Investigators determined that the present situation of the patient justifies chemotherapy plus immunotherapy as first-line treatment. Tumor tissue samples are CLDN18.2 positive detected by central laboratory ECOG performance status 0-1. The results of the laboratory tests must meet all criteria Life expectancy of at least 3 months. Exclusion Criteria: Known active central nervous system metastasis or suspected cancerous meningitis; There are moderate to large amounts of abdominal and pleural fluid. The presence of clinically uncontrollable third interspace fluid； Patients with any other malignant tumors within the past 5 years. Applicable to anti-HER-2 drug therapy； Anti-CLDN18.2 antibody, anti-PD-1 antibody, or drug therapy at any time in the past； Patients have received antitumor therapy during the first 4 weeks before study drug use; Pregnant or lactating women; or women of childbearing age who have a positive blood pregnancy test during screening period; or women of childbearing age and their spouses who are unwilling to take effective contraceptive measures during the period of this clinical trial and within 6 months after the end of the clinical trial;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASKB589 +CAPOX+Sintilimab<br>Oxaliplatin: intravenous infusion, 130mg/m2, infusion for more than 3h, every 3 weeks for a cycle, infusion 6 cycles; Capecitabine: oral administration, 1000mg/m2, 2 times, 14 days, 7 days rest, every 3 weeks for a cycle; Sintilimab was administered intravenously at 200mg. The drug was administered once every 3 weeks, and the longest cumulative duration was 2 years. ASKB589 is administered intravenously at a fixed dose. the drug was given once every 3 weeks for a cycle, with the longest cumulative duration of 2 years. | Drug: ASKB589 +CAPOX+Sintilimab<br>* Oxaliplatin: intravenous infusion, 130mg/m2, infusion for more than 3h, every 3 weeks for a cycle, infusion 6 cycles; Capecitabine: oral administration, 1000mg/m2, 2 times, 14 days, 7 days rest, every 3 weeks for a cycle; Sintilimab was administered intravenously at 200mg. The drug was administered once every 3 weeks, and the longest cumulative duration was 2 years. ASKB589 is administered intravenously at a fixed dose. the drug was given once every 3 weeks for a cycle, with the longest cumulative duration of 2 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as assessed by CTCAE v5.0 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be presented. | up to 21 days following last dose | 
| The incidence and case number of DLT (Dose Limiting Toxicity) during observation period. | DLT is short for Dose Limiting Toxicity，dose-limiting describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. | up to 21 days following last dose | 
| Maximum Tolerated Dose (MTD） | The MTD was defined as the highest dose of ASKB589 not causing DLT in more than 33% of patients in the first treatment cycle. | up to 21 days following last dose | 
| The recommended dose | The recommended dose will be determined during the dose escalation and dose expansion stage of the study. | from date of treatment start until data cut-off, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics:maximum Plasma Concentration [Cmax] | Serum samples will be collected for Cmax analysis. | Up to 21 days after injection | 
| Pharmacokinetics:time to maximum observed plasma concentration (Tmax) | Serum samples will be collected for Tmax analysis. | Up to 21 days after injection | 
| Pharmacokinetics:elimination rate constant（Kel） | Serum samples will be collected for Kel analysis | Up to 21 days after injection | 
| Pharmacokinetics:terminal elimination half life (T1/2) | Serum samples will be collected for T1/2 analysis. | Up to 21 days after injection | 
| Pharmacokinetics:apparent volume of distribution (Vz/F) | Serum samples will be collected for Vz/F analysis. | Up to 21 days after injection | 
| Pharmacokinetics:Area Under Curve (AUC) | Serum samples will be collected for AUC analysis. | Up to 21 days after injection | 
| Pharmacokinetics: Mean ResidenceTime（MRT） | Serum samples will be collected for MRT analysis. | Up to 21 days after injection | 
| Pharmacokinetics: plasma clearance rate (CL) | Serum samples will be collected for CL analysis. | Up to 21 days after injection | 
| Pharmacokinetics: steady-state peak concentration (Css_max) | Serum samples will be collected for Css_max analysis. | Up to 21 days after injection | 
| Pharmacokinetics: time to steady-state peak concentration (Tss_max) | Serum samples will be collected for Tss_max analysis. | Up to 21 days after injection | 
| Pharmacokinetics: minimum value of steady plasma drug concentration（Css_min） | Serum samples will be collected for Css max analysis. | Up to 21 days after injection | 
| Evaluation of immunogenicity | Incidence of anti-drug antibodies (ADA) | from date of treatment start until data cut-off, up to 2 years | 
| Objective response rate（ORR） | Evaluation of objective response rate assessed by RECIST 1.1 | from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years | 
| disease control rate（DCR) | Evaluation of Disease control rate assessed by RECIST 1.1 | from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years | 
| Duration of Response（DOR） | Duration of response assessed by RECIST 1.1 | from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years | 
| Progression free survival（PFS） | Progression of tumor will be measured by RECIST v1.1 | from date of treatment start until the date of disease progression or until death due to any causes, up to 2 years | 
| Overall survival（OS） | defined as the time from the date of treatment start until date of death due to any cause. | from the date of treatment start until the documented date of death from any cause，up to 2 years. |