TL938 plus trastuzumab for HER2-positive metastatic colorectal cancer

A Phase 2 Study to Evaluate TL938 Combined With Trastuzumab in Patients With HER2-positive Metastatic Colorectal Cancer

This Phase 2 test checks whether combining oral TL938 with trastuzumab helps adults with HER2-positive, RAS wild-type metastatic or unresectable colorectal cancer that has progressed after standard chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Suzhou Teligene Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, trastuzumab
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06589830 on ClinicalTrials.gov

What this trial studies

This Phase 2, interventional study combines TL938 capsules with trastuzumab to determine an optimal TL938 dose and measure anti-tumor activity and safety in HER2-positive metastatic colorectal cancer. Eligible patients are adults with RAS wild-type, HER2-positive disease that is unresectable or metastatic and previously treated with fluoropyrimidine, oxaliplatin, irinotecan, and an anti-VEGF antibody, with additional requirements for dMMR/MSI-H patients. Patients must have at least one measurable lesion, ECOG performance status 0–2, a life expectancy over three months, and adequate organ function. The trial is conducted at the Cancer Hospital, Chinese Academy of Medical Sciences in Beijing and will track response and tolerability to identify a recommended Phase 2 dose and preliminary efficacy signals.

Who should consider this trial

Good fit: Adults (≥18) with HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer who have received fluoropyrimidine, oxaliplatin, irinotecan, and an anti-VEGF antibody (and PD-1 antibody if dMMR/MSI-H), with measurable disease, ECOG 0–2, and adequate organ function are ideal candidates.

Not a fit: Patients who previously received anti-HER2 therapy, have recent systemic anti-cancer treatment within the prior 3 weeks, have poor organ function or a life expectancy ≤3 months, or who are RAS-mutant are unlikely to qualify or benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could offer a new HER2-targeted treatment option that shrinks tumors or controls disease in a subset of patients with heavily pretreated metastatic colorectal cancer.

How similar studies have performed: Other HER2-targeted combinations and HER2-directed agents have shown clinical activity in HER2-positive colorectal cancer, so this approach builds on prior positive signals in the field.

Eligibility criteria

Inclusion Criteria:

1. Age 18 years old and above, male or female;
2. Her2-positive, RAS wild-type, unresectable or metastatic colorectal cancer and prior treatment with fluoropyrimidine, oxaliplatin, irinotecan, and an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb). Patients whose tumors were deficient in mismatch repair (dMMR) proteins or were microsatellite instability-high (MSI-H) must also have received an ant-programmed cell death protain-1 mAb;
3. At least one measurable lesion;
4. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2;
5. A minimum life expectancy of \>3 months;
6. Adequate bone marrow reserve, hepatic, renal, and coagulation function;
7. Other inclusion criteria apply for participating in the Study. -

Exclusion Criteria:

1. Prior anti-HER2 targeting therapy;
2. Any systemic ant-tumor therapy such as chemotherapy and radiation therapy (including curative radiotherapy or spinal radiotherapy portion \>30%) used within 3 weeks prior to enrollment; immunotherapy within 4 weeks; any palliative radiotherapy for nan-target lesions used to relieve symptoms within 2 weeks prior to enrollment;
3. Participation in another interventional clinical trial 2 weeks prior to enrollment or within 5haIf-lives from the last dose of IP (whichever is shorter);
4. Surgical operation (excluding aspiration biopsy) of main organs or a significant injury within 4 weeks prior to enrollment;
5. Any unresolved toxicities from prior therapy greater than Grada 1, at the time of screening;
6. Active central nervous system (CNS) metastases. Asymptomatic CNS metastases with no steroid use within the last 30 days prior to enrollment is eligible;
7. Any other primary malignant tumors within 3 years (except for cured skin basal cell carcinoma and carcinoma in situ of cervix, low risk cancer such as low grade prostate cancer or ductal carcinoma in situ of the breast;
8. Any active infection which has not been controlled at screening;
9. Other exclusion criteria apply for participating in the Study. -

Where this trial is running

Beijing, Beijing Municipality

• Cancer Hospital, Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Xiaoyang Xia

Conditions Colorectal Cancer Metastatic; Advanced Colorectal Cancer; Oncology; TL938; Colorectal Cancer; HER2