A Clinical Study of TQB2930 Injection and Chemotherapy With or Without Bevacizumab in the Treatment of Advanced Colorectal Cancer

Official title

A Phase Ib/II Clinical Study to Evaluate the Efficacy and Safety of TQB2930 Injection and Chemotherapy With or Without Bevacizumab in Subjects With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Unresectable Locally Advanced or Metastatic Colorectal Cancer

Overview

To assess the safety and preliminary efficacy of TQB2930 and chemotherapy with or without bevacizumab in subjects with HER2-positive unresectable locally advanced or metastatic colorectal cancer (CRC).

Interventions

• Drug TQB2930 injection + Oxaliplatin injection + Capecitabine tablets + Bevacizumab injection
  TQB2930 enhances the binding to HER2 protein on the surface of tumor cells and increases HER2 internalization by simultaneously targeting ECD2 and ECD4, two non-overlapping epitopes of HER2 protein, which in turn more effectively down-regulates HER2 protein on the surface of tumor cells and dually blocks HER2 signaling. Oxaliplatin can block DNA replication and transcription and induce tumor cell apoptosis. Capecitabine inhibits thymidylate synthase (TS) and interferes with DNA synthesis. Bevaci
• Drug TQB2930 injection + Oxaliplatin injection + Capecitabine tablets
  TQB2930 enhances the binding to HER2 protein on the surface of tumor cells and increases HER2 internalization by simultaneously targeting Extracellular Domain 2 (ECD2) and Extracellular Domain 4 (ECD4), two non-overlapping epitopes of HER2 protein, which in turn more effectively down-regulates HER2 protein on the surface of tumor cells and dually blocks HER2 signaling. Oxaliplatin can block DNA replication and transcription and induce tumor cell apoptosis. Capecitabine inhibits thymidylate synth

Primary outcome measures

• Recommended Phase 2 Dose [Time frame: Baseline up to 21 days]
• Adverse event (AE) [Time frame: From the subject's signing of the informed consent form to 28 days after the last dose or the start of new anti-tumor therapy (whichever occurs first)]
• Objective Response Rate [Time frame: Baseline up to 24 months]

Secondary outcome measures (10)

• Half-life [Time frame: Baseline up to 24 months]
• Plasma concentration-time profiles [Time frame: Baseline up to 24 months]
• Apparent clearance [Time frame: Baseline up to 24 months]
• Apparent terminal volume of distribution [Time frame: Baseline up to 24 months]
• Trough plasma concentration [Time frame: Baseline up to 24 months]
• Disease Control Rate [Time frame: Baseline up to 24 months]
• Duration Of Response [Time frame: Baseline up to 24 months]
• Progression Free Survival [Time frame: Baseline up to 24 months]
• Overall Survival [Time frame: Baseline up to 24 months]
• Anti-Drug Antibodies (ADA) incidence [Time frame: Baseline up to 24 months]

Eligibility criteria

Inclusion criteria

• Subjects voluntarily participate in this study, sign the informed consent form, and have good compliance
• Age: 18-75 years (including the boundary when signing the informed consent form)
• Eastern Cooperative Oncology Group (ECOG) score: 0-1
• Expected survival of more than 3 months
• Unresectable locally advanced or metastatic colorectal cancer diagnosed by histopathology/cytology
• HER2 positive tested
• Presence of at least one measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Subjects should agree to use contraception during the study and for 6 months after the end

Exclusion criteria

• Patients with previously confirmed Microsatellite Instability Microsatellite Instability-High Deficient Mismatch Repair (MSI-H/dMMR)
• Presence of conditions affecting intravenous, venous blood sampling, or multiple factors affecting oral medications
• Active inflammatory bowel disease within 28 days prior to first dose
• Other malignancies within 5 years prior to the first dose or currently suffering from other malignancies
• Unresolved toxicity greater than CTCAE Grade 1 due to any prior therapy
• Major surgical treatment, significant traumatic injury within 28 days prior to the first dose or anticipation of major surgery during study treatment
• Had wounds or fractures that had not been healed for a long time
• Cerebrovascular accident, deep venous thrombosis and pulmonary embolism within 6 months prior to the first dose
• Patients with a history of psychotropic substance abuse who cannot quit or have mental disorders
• Subjects with any severe and/or uncontrolled disease
• Known tumor-related carcinomatous meningitis with symptoms of brain metastases or symptom control for less than 4 weeks
• Patients with imaging suggestive of tumor invasion of major blood vessels or fatal massive hemorrhage due to tumor rupture or invasion of major blood vessels judged by the investigator to be very likely to occur during the study
• Failure to control serous effusions requiring repeated drainage
• Local radiotherapy or 4. Bone marrow irradiation > 30% for bone metastasis before the first medication
• Known tumor-related spinal cord compression, weight-bearing bone pathological fracture, extensive bone metastasis, or uncontrollable tumor bone metastasis-related pain
• Patients who have received chemotherapy, targeted therapy, immunotherapy or other systemic anti-tumor drug therapy before the first medication;
• Received Chinese patent medicine treatment with anti-tumor indications in the package insert of National Medical Products Administration (NMPA) approved drugs before study treatment
• History of live attenuated vaccination before the first dose or planned live attenuated vaccination during the study;
• Previous history of severe allergy of unknown origin
• According to the investigator's judgment, there are concomitant diseases that seriously endanger the subject's safety or affect the completion of the study, or the subject is considered unsuitable for other reasons

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 24 centers

• Peking University First Hospital — Beijing
• Gansu Provincial Tumor Hospital — Lanzhou
• Guangxi Zhuang Autonomous Region Cancer Hospital — Nanning
• The Affiliated Hospital of Zunyi Medical University — Zunyi
• Harbin Medical University Cancer Hospital — Harbin
• Henan Cancer Hospital — Zhengzhou
• The first affiliated hospital of Zhengzhou university — Zhengzhou
• The Third People's Hospital of Zhengzhou — Zhengzhou
• … and 16 more centers

Identifiers

NCT: NCT07653685 · TQB2930-Ib/II-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗