Clinical Trial to Evaluate AB011 Injection in Patients With CLDN18.2-positive Advanced Solid Tumors

Overview

This is an open, two-stage, phase I study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of AB011 injection in patients with CLDN18.2-positive advanced solid tumors.

Full Title of Study: “An Open, Two-stage, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AB011 Injection in Patients With CLDN18.2-positive Advanced Solid Tumors”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 3, 2022

Detailed Description

This study is an open, two-stage, phase I study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of AB011 injection in patients with CLDN18.2-positive advanced solid tumors. The study is composed of two stages: stage I is for dose escalation and stage II is for dose expansion.

Interventions

  • Drug: AB011 Injection
    • AB011 Injection with dose escalation stage of 1mg/kg up to 40mg/kg, as well as dose expansion stage with recommended dose level from dose escalation stage.

Arms, Groups and Cohorts

  • Experimental: AB011 Injection
    • AB011 Injection treatment. This phase 1 trial will include two stages, a dose escalation stage and an expansion stage.

Clinical Trial Outcome Measures

Primary Measures

  • Incidence of adverse events (AE) of single and multiple dose (according to NCI CTCAE 5.0)
    • Time Frame: up to 8 months
    • 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.
  • Incidence of serious adverse events (SAE) of single and multiple dose (according to NCI CTCAE 5.0)
    • Time Frame: up to 8 months
    • An adverse event is any undesirable experience associated with the use of a medical product in a patient. The event is serious when the patient outcome is: Death; Life-threatening; Hospitalization (initial or prolonged); Disability or Permanent Damage; Congenital Anomaly/Birth Defect; Other Serious (Important Medical Events).
  • The incidence and case number of DLT (Dose Limiting Toxicity) during observation period
    • Time Frame: up to 28 days
    • 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.
  • Recommended Phase 2 Dose (RP2D)
    • Time Frame: Up to 1 Cycle after the last participant is enrolled in dose expansion phase (Approximately 2 years)
    • The RP2D will be determined during the dose expansion stage of the study. RP2D will be determined using available safety and efficacy data.

Secondary Measures

  • Pharmacokinetics: Area Under Curve (AUC) with immunoanalytical method
    • Time Frame: Up to 28 days after injection
    • AUC will be recorded from the PK serum samples collected.
  • Pharmacokinetics: plasma clearance rate (CL) with immunoanalytical method
    • Time Frame: Up to 28 days after injection
    • CL will be recorded from the PK serum samples collected.
  • Pharmacokinetics: minimum concentration (Cmin) with immunoanalytical method
    • Time Frame: Up to 28 days after injection
    • Cmin will be recorded from the PK serum samples collected.
  • Pharmacokinetics: maximum concentration (Cmax) with immunoanalytical method
    • Time Frame: Up to 28 days after injection
    • Cmax will be recorded from the PK serum samples collected.
  • Pharmacokinetics: half-life (T1/2) with immunoanalytical method
    • Time Frame: Up to 28 days after injection
    • T1/2 will be recorded from the PK serum samples collected.
  • Pharmacokinetics: apparent volume of distribution (Vd) with immunoanalytical method
    • Time Frame: Up to 28 days after injection
    • Vd will be recorded from the PK serum samples collected.
  • Immunogenicity
    • Time Frame: Up to 8 months (end of treatment)
    • Incidence of anti-drug antibodies
  • Efficacy: objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
    • Time Frame: Up to 8 months (end of treatment)
    • The ORR is defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1.
  • Efficacy: disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
    • Time Frame: Up to 8 months (end of treatment)
    • The DCR is defined as the proportion of subjects with complete or partial objective response, or stable disease based on RECIST V1.1.
  • Efficacy: duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
    • Time Frame: from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring, up to 8 months.
    • DOR is defined as the time from the date of the first response CR (complete remission)/PR (partial remission) (whichever is first recorded) to the date of radiographical progression/death or date of censoring.
  • Efficacy: progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
    • Time Frame: from date of treatment start until the date of radiological disease progression or until death due to any cause, up to 8 months.
    • PFS is defined as the time from date of treatment start until the date of radiological disease progression or until death due to any cause.
  • Efficacy: overall survival (OS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
    • Time Frame: from the date of treatment start until the documented date of death from any cause, up to 12 months.
    • OS is defined as the time from the date of treatment start until the documented date of death from any causes.

Participating in This Clinical Trial

Inclusion Criteria

  • 1. Aged 18 to 80 years, either sex;
  • 2. Patients with histologically or pathologically confirmed advanced solid tumors should have failed the standard treatment, or have no standard treatment regimen available, or have no access to standard treatment;
  • 3. Tumor tissue samples is CLDN18.2 positive detected by central laboratory;
  • 4. According to RECIST1.1, there are at least one evaluable tumor lesion during dose escalation period (period 1), and at least one measurable tumor lesion during dose expansion period (period 2);
  • 5. The ECOG score is 0 to 1;
  • 6. Expected survival > 3 months;
  • 7. Various organs in good condition;
  • 8. Fertile eligible patients (male and female) and their partners are willing to use a reliable method of contraception (hormones, barriers or abstinence) during the study and within 90 days after the last study treatment; women of childbearing potential must be tested for serum or urine pregnancy within 7 days before enrollment with negative results;
  • 9. Patients are informed of this study before the trial and sign written informed consent form.

Exclusion Criteria

  • 1. Received anti-tumor therapies within 4 weeks prior to first administration of study drug, except: within 6 weeks for nitrosoureas or mitomycin C, within 2 weeks or 5 half-life of drugs (whichever longer) for oral fluorouracils and small molecular targeted drugs, and within 2 weeks for traditional Chinese medicines with indications of anti-tumor;
  • 2. Received other non-marketed clinical trial drugs within 4 weeks prior to first administration of study drugs;
  • 3. Received major surgery or had significant trauma within 4 weeks prior to first administration of study drug;
  • 4. Received systemic corticosteroids or other immunosuppressors within 14 days prior to first administration of study drug;
  • 5. Patients with AEs from previous treatment that have not recovered to CTCAE 5.0 ≤1;
  • 6. Patients have central nervous system (CNS) metastasis or meningeal metastasis, or other evidences which demonstrate the CNS metastasis or meningeal metastasis are not controlled, resulting that patients are not eligible for enrollment at the investigator's discretion;
  • 7. Patients with any active infection which requires systemic treatment with of anti-infection currently;
  • 8. Patients with medical history of immune deficiency;
  • 9. Patients with hepatitis B; with HCV infection;
  • 10. Patients have interstitial lung disease at present, or had medical history of interstitial lung disease;
  • 11. Patients have significant medical history of cardiovascular and cerebrovascular diseases;
  • 12. Have high risks of gastrointestinal hemorrhage at the investigator's discretion;
  • 13. Patients who need long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) ;
  • 14. Known alcohol use or drug dependence;
  • 15. Patients with mental disorders or poor compliance;
  • 16. Pregnant or lactating women;
  • 17. Patients have other serious systemic diseases or cannot participate in this trial due to other reasons, at the investigator's discretion.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Carsgen Therapeutics, Ltd.
  • Collaborator
    • Shanghai East Hospital
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jin Li, Principal Investigator, Shanghai East Hospital
  • Overall Contact(s)
    • Zonghai Li, Dr., 86-21-64355922, zonghaili@carsgen.com

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