TQB2922 and TAS-102 Tablets for Injection With or Without Bevacizumab in Chemotherapy-failed RAS/BRAF Wild-type Advanced Colorectal Cancer

Официальное название

A Phase Ib/II Clinical Study Evaluating TQB2922 for Injection and Chemotherapy in Combination With or Without Bevacizumab in Subjects With RAS/BRAF Wild-Type Advanced Colorectal Cancer Who Have Failed Chemotherapy

Обзор

This is a multicenter, open Phase Ib/II clinical study evaluating the safety and efficacy of TQB2922 in combination with TAS-102±bevacizumab in subjects with RAS/BRAF wild-type unresectable locally advanced or metastatic colorectal cancer that has failed treatment with oxaliplatin, fluorouracil-based and irinotecan.

Вмешательства

• Препарат TQB2922 injection ± TAS-102 tablets
  TQB2922 is an anti-EGFR/c-Met bispecific antibody, subtype Immunoglobulin G1 (IgG1). TQB2922 blocks the activation of EGFR and c-Met signalling pathway by binding to EGFR and c-Met on the surface of tumour cells, thus preventing tumour growth and progression. At the same time, TQB2922 can target EGFR and c-Met on the surface of tumour cells through antibody-dependent cytotoxicity (ADCC) and antibody-dependent cell phagocytosis by natural killer cells and macrophages, thus killing tumour cells.
• Препарат TQB2922 injection+TAS-102 tablets ± Bevacizumab
  TQB2922 is an anti-EGFR/c-Met bispecific antibody, subtype IgG1. TQB2922 blocks the activation of EGFR and c-Met signalling pathway by binding to EGFR and c-Met on the surface of tumour cells, thus preventing tumour growth and progression. At the same time, TQB2922 can target EGFR and c-Met on the surface of tumour cells through antibody-dependent cytotoxicity (ADCC) and antibody-dependent cell phagocytosis by natural killer cells and macrophages, thus killing tumour cells.

Первичные конечные точки

• Dose limiting toxicity (DLT) [Срок оценки: Baseline up to 48 weeks]
• Objective Response Rate (ORR) [Срок оценки: Complete response time was achieved, evaluation is expected to take 1 years.]

Вторичные конечные точки (12)

• Maximum tolerated dose (MTD) [Срок оценки: Baseline up to 48 weeks]
• Incidence of adverse event (AE) and serious adverse event (SAE) [Срок оценки: Baseline up to 48 weeks]
• Disease Control Rate (DCR) [Срок оценки: Complete response time was achieved, evaluation is expected to take 1 years.]
• Recommended Phase 2 Dose [Срок оценки: Baseline up to 48 weeks]
• Elimination Half-life [Срок оценки: Baseline up to 48 weeks]
• Area Under the Curve [Срок оценки: Baseline up to 48 weeks]
• Apparent Clearance [Срок оценки: Baseline up to 48 weeks]
• Apparent Volume of Distribution in Terminal Phase [Срок оценки: Baseline up to 48 weeks]
• Trough Concentration [Срок оценки: Baseline up to 48 weeks]
• Duration of Response [Срок оценки: Complete response time was achieved, evaluation is expected to take 1 years.]
• Progression-Free Survival [Срок оценки: 1 year of assessment is expected from the start of enrolment to the first occurrence of disease progression or death from any cause]
• Incidence of Anti-Drug Antibody [Срок оценки: Baseline up to 48 weeks]

Критерии участия

Критерии включения

• Subjects voluntarily enrolled in the study, signed the informed consent and had good compliance;
• Age: 18-75 years old (including boundaries at the time of signing the informed consent);
• Eastern Cooperative Oncology Group (ECOG) score: 0-1;
• Expected survival of more than 3 months;
• Unresectable locally advanced or metastatic colorectal cancer diagnosed by histological/cytological pathology;
• Disease progression or intolerable after prior treatment with oxaliplatin, fluorouracil-based and irinotecan and treated with cetuximab or bevacizumab;
• Patients with genetic testing showing wild-type for both rat sarcoma (RAS) and B-type rapid response protein kinase (BRAF);
• Presence of at least 1 measurable lesion according to RECIST 1.1 criteria;
• Laboratory tests meet the criteria;
• Female subjects of childbearing potential must agree to use contraception (e.g., Intrauterine Device (IUD), birth control pills, or condoms) for the duration of the study and for 6 months after the end of the study; must have a negative serum pregnancy/urine pregnancy test
• within 7 days prior to study entry and must not be breastfeeding; male subjects must agree to use contraception for the duration of the study and for 6 months after the end of the study.

Критерии исключения

• Patients who have had previous confirmation of microsatellite high instability/mismatch repair defects (MSI-H/dMMR) by immunohistochemistry (IHC), next-generation sequencing (NGS) or polymerase chain reaction (PCR);
• Presence of a disease that interferes with intravenous administration, intravenous blood collection, or multiple factors that interfere with oral administration of medications (e.g., inability to swallow, chronic diarrhoea and intestinal obstruction);
• Active inflammatory bowel disease (ulcerative colitis, Crohn's disease) within 28 days prior to first dose;
• The presence or current concurrent presence of other malignancies within 2 years prior to the first dose.
• Unresolved toxic reactions above Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 due to any prior therapy, excluding alopecia, fatigue and peripheral neuropathy;
• Major surgical treatment, incisional biopsy or significant traumatic injury within 28 days prior to first dose;
• The presence of a long-standing unhealed wound or fracture;
• Cerebrovascular accident (including temporary ischaemic attack, cerebral haemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism within 6 months prior to the first dose;
• Have a history of psychotropic substance abuse and are unable to quit or have a mental disorder;
• Subjects with any severe and/or uncontrolled medical condition, including:

• Unsatisfactory control of blood pressure (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg, at least 2 measurements taken at intervals of more than 24h);
• Myocardial infarction, unstable angina pectoris, stable angina pectoris ≥ Grade 2, heart failure ≥ Grade 2 (New York Heart Association (NYHA) classification), arrhythmia ≥ Grade 2;
• Active or uncontrolled severe bacterial, viral, or systemic fungal infection (≥ CTC AE grade 2 infection) within 28 days prior to first dose; patients with active tuberculosis within 1 year prior to enrolment.
• Active viral hepatitis with poor control. Subjects will be screened if they meet the following requirements: Hepatitis B surface antigen (HBsAg) positive subjects with Hepatitis B virus (HBV) DNA quantification <2000 IU/ml (or 1\*10 4 copy/ml) or at least 1 week of anti-HBV treatment with a 10-fold (1 log) or greater reduction in viral index prior to study entry. Subject is willing to remain on anti-HBV therapy for the entire duration of the study; HCV-infected patients (HCV Ab or HCV RNA positive) who are judged to be stable by the investigator or who are on antiviral therapy at the time of enrolment and who continue to receive approved antiviral therapy during the study;
• Subjects with a history of (non-infectious) interstitial lung disease requiring systemic steroid therapy, or current interstitial lung disease/interstitial pneumonia; or subjects with Screening Imaging suggestive of suspected interstitial lung disease/interstitial pneumonia that cannot be ruled out;
• History of immunodeficiency, including being human immunodeficiency virus (HIV) positive or having other acquired, congenital immunodeficiency diseases;
• Poorly controlled diabetes mellitus (fasting blood glucose (FBG) > 10 mmol/L); and
• Active syphilis infection.
• Known tumour-associated spinal cord compression, cancerous meningitis, with symptoms of brain metastases, or symptoms controlled for less than 4 weeks;
• Imaging suggestive of tumour invasion of large blood vessels or, in the judgement of the investigator, there is a high probability of tumour rupture or invasion of vital blood vessels during the study period leading to fatal haemorrhage;
• Failure to control a plasma (thoracic, abdominal, or pericardial) effusion that requires repeated drainage;
• Local radiotherapy within 2 weeks or >30% bone marrow irradiation radiotherapy for bone metastases within 4 weeks prior to first dose.
• Chemotherapy, targeted therapy, immunotherapy, or other antineoplastic agents within 4 weeks prior to the first dose, or who are still on drug 5.

treatment, or subjects who are still within 5 half-lives of the drug (whichever occurs first);

• Prior use of epidermal growth factor receptor/c-mesenchymal epidermal transforming factor (EGFR/c-Met) dual-antibody drugs;
• Received treatment with a proprietary Chinese medicine with an anti-tumour indication as specified in the National Drug
• Administration (NMPA) approved drug insert within 1 week prior to study treatment.
• History of live attenuated vaccination within 2 weeks prior to the first dose or planned live attenuated vaccination during the study period.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 27 центров

• The First Affiliated Hospital of Anhui Medical University — Хэфэй
• National Cancer Center/Chinese Academy of Medical Sciences Cancer Hospital — Пекин
• The First Affiliated Hospital of Chongqing Medical University — Чунцин
• Zhongshan Hospital Affiliated to Xiamen University — Xiamen
• The Third Affiliated Hospital of Sun Yat-sen University — Гуанчжоу
• Meizhou People's Hospital — Meizhou
• Shantou University Medical College Affiliated Cancer Hospital — Shantou
• Guangxi Zhuang Autonomous Region Cancer Hospital — Nanning
• … и ещё 19 центров

Идентификаторы

NCT: NCT07044908 · TQB2922-Ib/II-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗