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

NCT04400383 | Completed Phase 1

• 1 other identifier: AB011-ST-01
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Solid Tumor; Gastric Cancer; Pancreatic Adenocarcinoma

Keywords

advanced solid tumors; Gastric Cancer; Esophagogastric Junction Cancer; Pancreatic Adenocarcinoma; Claudin 18.2; CLDN18.2; monoclonal antibody

Outcome Measures

Primary Outcomes (6)

• Stage1：Incidence of adverse events AE of single and multiple dose (according to NCI CTCAE 5.0)

  An AE or SAE 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.

  From First dose to last patient progression or 6 months, whichever came first

• Stage1：Incidence of adverse events SAE of single and multiple dose (according to NCI CTCAE 5.0)

  An AE or SAE 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.

  From First dose to last patient progression or 6 months, whichever came first

• Stage 1: 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.

  From first dose up to 28 days

• Stage 2：Incidence of adverse events AE of single and multiple dose for AB011 combinate with XELOX or Gem/nab-P (according to NCI CTCAE 5.0)

  An AE or SAE 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.

  From First dose to last patient progression or 12 months, whichever came first

• Stage 2：Incidence of adverse events SAE of single and multiple dose for AB011 combinate with XELOX or Gem/nab-P (according to NCI CTCAE 5.0)

  An AE or SAE 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.

  From First dose to last patient progression or 12 months, whichever came first

• Stage 2: 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.

  From first dose up to 21 days

Secondary Outcomes (18)

• Stage 1: Pharmacokinetics: Area Under Curve (AUC) with immunoanalytical method

  Up to progression of disease after injection, or end of 6 cycle( each cycle is 28 days), whichever came first

• Stage 2: Pharmacokinetics: Area Under Curve (AUC) with immunoanalytical method

  Up to progression of disease after injection, or end of cycle 6 (each cycle is 21 days), whichever came first

• Stage 1: Pharmacokinetics: clearance rate (CL) with immunoanalytical method

  Up to progression of disease after injection, or 6 cycle( dose increase), 8 cycle (dose extension), whichever came first

• Stage 2: Pharmacokinetics: clearance rate (CL) with immunoanalytical method

  Up to progression of disease after injection, or end of cycle 6 (each cycle is 21 days), whichever came first

• Stage 1: Pharmacokinetics: minimum concentration (Cmin) with immunoanalytical method

  Up to progression of disease after injection, or end of cycle 6（dose increase stage), or cycle 8 (dose expansion stage), each cycle is 28 days, whichever came first

Study Arms (1)

AB011 Injection

EXPERIMENTAL

AB011 Injection treatment. This phase 1 trial will include two stages, a single treatment stage and a Combo treatment stage.

Drug: AB011 Injection

Interventions

AB011 Injection DRUG

Stage 1 Single treatment: AB011 Injection with dose escalation of 1mg/kg up to 40mg/kg, as well as dose expansion with recommended dose level from dose escalation. Stage 2 Combo Treatment: AB011 combine XELOX( GC) or Gem/nab-P (PC) Injection with dose escalation of 10mg/kg up to 30mg/kg, as well as dose expansion with recommended dose level from dose escalation.

Also known as: recombinant humanized anti-Claudin 18.2 monoclonal antibody injection, recombinant humanized anti-CLDN 18.2 monoclonal antibody injection

AB011 Injection

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Aged 18 to 80 years, either sex;
• \. Patients with histologically or cytologic confirmed advanced solid tumors should have failed the standard treatment, or have no standard treatment regimen available, or have no access to standard treatment;
• \. Tumor tissue samples is CLDN18.2 positive;
• \. According to RECIST1.1, there are at least one evaluable tumor lesion during dose escalation period (stage 1), and at least one measurable tumor lesion during dose expansion period (stage 2);
• \. The ECOG score is 0 to 1;
• \. Expected survival \> 3 months;
• \. Various organs in good condition;
• \. 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;
• \. Patients are informed of this study before the trial and sign written informed consent form.

You may not qualify if:

• \. 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;
• \. Received other non-marketed clinical trial drugs within 4 weeks prior to first administration of study drugs;
• \. Received major surgery or had significant trauma within 4 weeks prior to first administration of study drug;
• \. Received systemic corticosteroids or other immunosuppressors within 14 days prior to first administration of study drug;
• \. Patients with AEs from previous treatment that have not recovered to ≤1 (CTCAE 5.0 );
• \. 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;
• \. Patients with any active infection which requires systemic treatment with of anti-infection currently;
• \. Patients with medical history of immune deficiency;
• \. Patients with hepatitis B;
• Patients with HCV infection but who with the HCV-RNA lower than the lower limit of detection can be enrolled ;
• Patients with interstitial lung disease or Pulmonary function abnormalities which were identified by the investigator as clinically significant;
• Patients who received any anti-CLDN18.2 treatment;
• Patients with significant medical history of cardiovascular and cerebrovascular diseases;
• Patient with high risks of gastrointestinal hemorrhage at the investigator's discretion;
• Patients who need long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) ;

Sponsors & Collaborators

• CARsgen Therapeutics Co., Ltd.: lead
• Shanghai East Hospital: collaborator

Study Sites (12)

Anhui Provincial Hospital

Hefei, Anhui, 230036, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

Location

Huaihua Second People's Hospital

Huaihua, Hunan, 418099, China

Location

Linyi Cancer Hospital

Linyi, Shandong, 276002, China

Location

Zhongshan Hospital, Zhongshan University

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200123, China

Location

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

Sir Run Run Shaw Hospital

Hangzhou, Zhejiang, 310016, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Jin Li

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2020
• First Posted: May 22, 2020
• Study Start: June 4, 2020
• Primary Completion: July 8, 2023
• Study Completion: September 28, 2023
• Last Updated: May 24, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (12)