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

Primary Purpose

Gastric Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ASKB589 +CAPOX+Sintilimab
Sponsored by
AskGene Pharma, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Beijing Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ASKB589 +CAPOX+Sintilimab

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
The recommended dose
The recommended dose will be determined during the dose escalation and dose expansion stage of the study.

Secondary Outcome Measures

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

Full Information

First Posted
November 21, 2022
Last Updated
February 15, 2023
Sponsor
AskGene Pharma, Inc.
Collaborators
Jiangsu Aosaikang Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05632939
Brief Title
ASKB589 in Combination With CAPOX and Sintilimab in Patients With Advanced, and Unresectable G/GEJ Cancer.
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2023 (Actual)
Primary Completion Date
February 10, 2025 (Anticipated)
Study Completion Date
February 10, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AskGene Pharma, Inc.
Collaborators
Jiangsu Aosaikang Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
57 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ASKB589 +CAPOX+Sintilimab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ASKB589 +CAPOX+Sintilimab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of participants with adverse events as assessed by CTCAE v5.0
Description
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.
Time Frame
up to 21 days following last dose
Title
The incidence and case number of DLT (Dose Limiting Toxicity) during observation period.
Description
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.
Time Frame
up to 21 days following last dose
Title
Maximum Tolerated Dose (MTD)
Description
The MTD was defined as the highest dose of ASKB589 not causing DLT in more than 33% of patients in the first treatment cycle.
Time Frame
up to 21 days following last dose
Title
The recommended dose
Description
The recommended dose will be determined during the dose escalation and dose expansion stage of the study.
Time Frame
from date of treatment start until data cut-off, up to 2 years
Secondary Outcome Measure Information:
Title
Pharmacokinetics:maximum Plasma Concentration [Cmax]
Description
Serum samples will be collected for Cmax analysis.
Time Frame
Up to 21 days after injection
Title
Pharmacokinetics:time to maximum observed plasma concentration (Tmax)
Description
Serum samples will be collected for Tmax analysis.
Time Frame
Up to 21 days after injection
Title
Pharmacokinetics:elimination rate constant(Kel)
Description
Serum samples will be collected for Kel analysis
Time Frame
Up to 21 days after injection
Title
Pharmacokinetics:terminal elimination half life (T1/2)
Description
Serum samples will be collected for T1/2 analysis.
Time Frame
Up to 21 days after injection
Title
Pharmacokinetics:apparent volume of distribution (Vz/F)
Description
Serum samples will be collected for Vz/F analysis.
Time Frame
Up to 21 days after injection
Title
Pharmacokinetics:Area Under Curve (AUC)
Description
Serum samples will be collected for AUC analysis.
Time Frame
Up to 21 days after injection
Title
Pharmacokinetics: Mean ResidenceTime(MRT)
Description
Serum samples will be collected for MRT analysis.
Time Frame
Up to 21 days after injection
Title
Pharmacokinetics: plasma clearance rate (CL)
Description
Serum samples will be collected for CL analysis.
Time Frame
Up to 21 days after injection
Title
Pharmacokinetics: steady-state peak concentration (Css_max)
Description
Serum samples will be collected for Css_max analysis.
Time Frame
Up to 21 days after injection
Title
Pharmacokinetics: time to steady-state peak concentration (Tss_max)
Description
Serum samples will be collected for Tss_max analysis.
Time Frame
Up to 21 days after injection
Title
Pharmacokinetics: minimum value of steady plasma drug concentration(Css_min)
Description
Serum samples will be collected for Css max analysis.
Time Frame
Up to 21 days after injection
Title
Evaluation of immunogenicity
Description
Incidence of anti-drug antibodies (ADA)
Time Frame
from date of treatment start until data cut-off, up to 2 years
Title
Objective response rate(ORR)
Description
Evaluation of objective response rate assessed by RECIST 1.1
Time Frame
from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years
Title
disease control rate(DCR)
Description
Evaluation of Disease control rate assessed by RECIST 1.1
Time Frame
from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years
Title
Duration of Response(DOR)
Description
Duration of response assessed by RECIST 1.1
Time Frame
from date of treatment start until disease progression,date of death or withdrawal from study,whichever came first, up to 2 years
Title
Progression free survival(PFS)
Description
Progression of tumor will be measured by RECIST v1.1
Time Frame
from date of treatment start until the date of disease progression or until death due to any causes, up to 2 years
Title
Overall survival(OS)
Description
defined as the time from the date of treatment start until date of death due to any cause.
Time Frame
from the date of treatment start until the documented date of death from any cause,up to 2 years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dong Han
Phone
025-8509062
Email
handong@ask-pharm.com
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100089
Country
China
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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