Clinical Trial Evaluating the Safety of the TQB2103 for Injection

NCT05867563 | Unknown Phase 1

• 1 other identifier: TQB2103-I-01
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 4

Brief Summary

TQB2103 injection is an antibody-drug conjugate (ADC) targeting claudin (CLDN) 18.2. This study aimed to evaluate the safety and tolerability, pharmacokinetic characteristics and immunogenicity of TQB2103 injection in patients with advanced malignant tumors as well as its initial effectiveness.

Conditions

Advanced Malignant Neoplasm

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT)

  DLT was defined as toxicities that meet pre-defined severity criteria according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0, and assessed as having suspected relationship to investigational drug that occurred within the first treatment cycle (21 days).

  During the first treatment cycle (21 days).

• Maximum tolerated dose (MTD)

  MTD was defined as the highest dose at which dose limiting toxicity (DLT) occurred in less than 33% of patients.

  During the first treatment cycle (21 days).

• Recommended Phase II Dose (RP2D)

  The RP2D of anticancer agents is determined traditionally by dose-limiting toxicities. Nontoxicity or biological endpoints such as pharmacokinetics, pharmacodynamics, and efficacy can also be used to identify RP2D.

  During the first treatment cycle (21 days).

Secondary Outcomes (12)

• The area under the curve (AUC)

  2 hours pre-dose, 0, 2, 4, 7, 24, 72, 144, 312, 504 hours (when necessary) after dose on cycle 1 and cycle 3; 2 hours pre-dose, 0 hour, 504 hours (when necessary) after dose on cycle 2, cycle 4, cycle 6, cycle 8. Each cycle is 21 days.

• Peak concentration (Cmax)

  2 hours pre-dose, 0, 2, 4, 7, 24, 72, 144, 312, 504 hours (when necessary) after dose on cycle 1 and cycle 3; 2 hours pre-dose, 0 hour, 504 hours (when necessary) after dose on cycle 2, cycle 4, cycle 6, cycle 8. Each cycle is 21 days.

• Immunogenicity

  120 minutes pre-dose on Cycle 1 Day 1, Cycle 2 Day1, Cycle 4 Day1, Cycle 7 Day1, Cycle 12 Day1; 90 days after the last infusion. Each cycle is 21 days.

• Terminal half-life (T1/2)

  2 hours pre-dose, 0, 2, 4, 7, 24, 72, 144, 312, 504 hours (when necessary) after dose on cycle 1 and cycle 3; 2 hours pre-dose, 0 hour, 504 hours (when necessary) after dose on cycle 2, cycle 4, cycle 6, cycle 8. Each cycle is 21 days.

• Apparent Clearance (CL/F)

  2 hours pre-dose, 0, 2, 4, 7, 24, 72, 144, 312, 504 hours (when necessary) after dose on cycle 1 and cycle 3; 2 hours pre-dose, 0 hour, 504 hours (when necessary) after dose on cycle 2, cycle 4, cycle 6, cycle 8. Each cycle is 21 days.

Study Arms (1)

TQB2103 for Injection

EXPERIMENTAL

Dose escalation: intravenous infusion of TQB2103 for injection once every three weeks, 21 days as one treatment cycle. (0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 3.0 mg/kg, 4.0 mg/kg, 5.0mg/kg) Dose expansion: Chose one or two appropriate dose groups in the dose escalation experiment to expand.

Drug: TQB2103 for injection

Interventions

TQB2103 for injection DRUG

TQB2103 for injection is an antibody-drug conjugate targeting CLDN18.2. The drug structure mainly includes anti-humanized CLDN 18.2 antibody, linker and cytotoxic DDDXD, with Drug antibody Ratio (DAR) of 8.

TQB2103 for Injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced malignant tumours confirmed by histology or cytology, disease progression or intolerance after adequate standard treatment, or lack of standard treatment options, or standard treatment is not applicable currently .
• Age: 18-75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0-1; The expected survival time is more than 3 months.
• Patients who can provide fresh-collected or stored tumour tissue samples within 2 years for Claudin 18.2 expression level detection were preferentially enrolled, and those who cannot provide samples during the dose-escalation stage were also eligible to participate in the study; In the dose-expansion stage, subjects who could not provide tumour tissue samples for Claudin 18.2 expression level detection needed to be discussed with the investigators on a case-by-case basis, and enrollment may be allowed according to the specific situation.
• At least one evaluable tumour lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 in the dose-escalation study and at least one measurable lesion in the dose-expansion study (the lesion that received radiotherapy can be used as the target lesion after definite progression according to RECIST v1.1 evaluation).
• Good function of major organs.
• Fertile subjects should agree that contraception must be used during the study and for 6 months after the end of the study; Women of childbearing age had a negative serum pregnancy test within 7 days prior to study enrollment and had to be non-lactating subjects.
• Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.

You may not qualify if:

• Comorbidities and medical history:
• Have developed or are currently concurrent with other malignant tumors within the past 5 years.
• Have a high risk of Gastrointestinal (GI) bleeding, or have active severe GI disease.
• Patients with current interstitial lung disease or pulmonary fibrosis, pneumoconiosis, radiation pneumonitis, severe impairment of lung function, etc., which may interfere with the detection and management of suspected drug-related pulmonary toxicity.
• All reversible adverse events caused by any previous treatment have not recovered to CTCAE 5.0 grade ≤ grade 1, before the first dose of the investigational drug.
• Major surgical treatment, open biopsy, or significant traumatic injury within 4 weeks before the start of study treatment; Elective surgery was required during the trial; Or have wounds, ulcers or fractures that have not healed for a long time.
• Occurrence of arterial/venous thrombosis events within 6 months, such as cerebrovascular accident, deep vein thrombosis, and pulmonary embolism; People who have a history of psychotropic drug abuse and cannot abstain from it or have mental disorders.
• Subjects with any severe and/or uncontrolled illness.
• Cancer-related symptoms and treatment:
• Received systemic antineoplastic therapy such as radical surgery, chemotherapy, radical radiotherapy or immunotherapy, biological therapy or participated in Clinical trials of other interventional antineoplastic drugs within 4 weeks before the initiation of study treatment.
• Prior therapy against the Claudin18.2 target, such as Claudin18.2 monoclonal antibodies, bispecific antibody, ADC, or chimeric antigen receptor T-cell immunotherapy (CAR-T).
• Tumour has invaded important blood vessels on imaging (Computed Tomography (CT) or Magnetic Resonance Imaging(MRI)) or judged by the investigator to be highly likely to invade important blood vessels during the follow-up study.
• Poorly controlled pleural, pericardial or peritoneal effusion requiring repeated drainage, judged by the investigator to be unsuitable for enrollment.
• Subjects with known active central nervous system metastases and/or meningeal metastases or spinal cord compression.
• Study treatment-related:

Sponsors & Collaborators

• Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.: lead

Study Sites (4)

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

RECRUITING

Xuzhou Central Hospital

Xuzhou, Jiangsu, 221111, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

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 9, 2023
• First Posted: May 22, 2023
• Study Start: July 4, 2023
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: July 10, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)