TQB2922 with TAS-102, with or without bevacizumab, for chemo‑resistant RAS/BRAF wild‑type advanced colorectal cancer

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

This study will test whether adding the experimental drug TQB2922 to TAS‑102, with or without bevacizumab, helps people with RAS/BRAF wild‑type advanced colorectal cancer that has stopped responding to standard chemotherapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Industry-sponsored)
• Drugs / interventions: cetuximab, bevacizumab, Chemotherapy, immunotherapy
• Locations: 27 sites (Hefei, Anhui and 26 other locations)
• Trial ID: NCT07044908 on ClinicalTrials.gov

What this trial studies

This multicenter, open‑label Phase Ib/II study administers TQB2922 together with TAS‑102, with optional bevacizumab, to adults with unresectable locally advanced or metastatic RAS/BRAF wild‑type colorectal cancer who have progressed after oxaliplatin-, fluorouracil‑, and irinotecan‑based regimens. The Phase Ib portion focuses on safety and dose finding, followed by a Phase II expansion to look for preliminary antitumor activity. Eligible patients must have ECOG 0–1, measurable disease per RECIST 1.1, and prior exposure to cetuximab or bevacizumab. The trial will monitor tolerability, adverse events, and signals of tumor response or disease control.

Who should consider this trial

Good fit: Adults aged 18–75 with unresectable locally advanced or metastatic RAS/BRAF wild‑type colorectal cancer, ECOG 0–1, measurable disease, expected survival >3 months, and disease progression after oxaliplatin-, fluorouracil‑based and irinotecan therapies with prior cetuximab or bevacizumab are the intended candidates.

Not a fit: Patients with RAS or BRAF mutations, poor performance status (ECOG ≥2), life expectancy under three months, or medical contraindications to the study drugs are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could offer a new treatment option that shrinks tumors or delays progression for patients whose RAS/BRAF wild‑type colorectal cancer no longer responds to standard chemotherapy.

How similar studies have performed: TAS‑102 is an approved option for refractory metastatic colorectal cancer and combinations of TAS‑102 with bevacizumab have shown benefit in prior trials, but TQB2922 is a novel agent and its use in combination with TAS‑102 is investigational.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Where this trial is running

Hefei, Anhui and 26 other locations

• The First Affiliated Hospital of Anhui Medical University — Hefei, Anhui, China (Not_yet_recruiting)
• National Cancer Center/Chinese Academy of Medical Sciences Cancer Hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• The First Affiliated Hospital of Chongqing Medical University — Chongqing, Chongqing Municipality, China (Not_yet_recruiting)
• Zhongshan Hospital Affiliated to Xiamen University — Xiamen, Fujian, China (Not_yet_recruiting)
• The Third Affiliated Hospital of Sun Yat-sen University — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Meizhou People's Hospital — Meizhou, Guangdong, China (Not_yet_recruiting)
• Shantou University Medical College Affiliated Cancer Hospital — Shantou, Guangdong, China (Not_yet_recruiting)
• Guangxi Zhuang Autonomous Region Cancer Hospital — Nanning, Guangxi, China (Not_yet_recruiting)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (Not_yet_recruiting)
• Xinyang Central Hospital — Xinyang, Henan, China (Not_yet_recruiting)
• Zhoukou Central Hospital — Zhoukou, Henan, China (Not_yet_recruiting)
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• Jiangsu Cancer Hospital — Nanjing, Jiangsu, China (Not_yet_recruiting)
• Jiangsu Provincial People's Hospital — Nanjing, Jiangsu, China (Not_yet_recruiting)
• Suzhou Municipal Hospital — Suzhou, Jiangsu, China (Not_yet_recruiting)
• Jiangnan University Affiliated Hospital — Wuxi, Jiangsu, China (Not_yet_recruiting)
• Jiangxi Cancer Hospital — Nanchang, Jiangxi, China (Not_yet_recruiting)
• Jilin Cancer Hospital — Changchun, Jilin, China (Not_yet_recruiting)
• The First Affiliated Hospital of China Medical University — Shenyang, Liaoning, China (Not_yet_recruiting)
• The First Affiliated Hospital of Xi'an Jiaotong University — Xi'an, Shaanxi, China (Not_yet_recruiting)
• Shandong Public Health Clinical Center — Jinan, Shandong, China (Not_yet_recruiting)
• Qingdao Municipal Hospital — Qingdao, Shandong, China (Recruiting)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Renji Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• The First Hospital of Shanxi Medical University — Taiyuan, Shanxi, China (Not_yet_recruiting)
• Yibin First People's Hospital — Yibin, Sichuan, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Suxia Luo, Master

Conditions RAS/BRAF Wild Type Colorectal Cancer