TL938 and Trastuzumab for Patients With HER2-positive Metastatic Colorectal Cancer

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

This is a Phase II trial designed to determine the optimal dose and evaluate the effectiveness of TL938 and trastuzumab in treating patients with HER2+ colorectal cancer that has metastasized or recurred and is inoperable.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Metastatic; Advanced Colorectal Cancer
• Intervention / Treatment: Drug: TL938 Capsules; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoyang Xia; Phone Number: 8053009373; Email: xiaoyang.xia@teligene.com
• Study Contact Backup: Name: Liling Ding; Phone Number: 15295298995; Email: liling.ding@medolution.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Cancer hospital, Chinese Academy of Medical Sciences
      • Contact: Yuankai Shi, Doctor of Medicine; Phone Number: 8610-67781331; Email: syuankaipumc@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TL938-Trastuzumab combination; TL938-Trastuzumab combination receives TL938 capsules by mouth once daily. Trastuzumab given intravenously on Day 1 of each Cycle. Cycle length is 21 days	Drug: TL938 Capsules; Oral administration; Drug: Trastuzumab; Intravenous (IV) infusion
Experimental: TL938; TL938 monotherapy receives TL938 capsules by mouth once daily. Cycle length is 21 days.	Drug: TL938 Capsules; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose limiting toxicity, maximum tolerated dose, and recommended phase 2 dose	Pre-dose up to approximately 24 months post-dose
Objective Response Rate (ORR) by IRC	Pre-dose up to approximately 24 months post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response (DoR)	Pre-dose up to approximately 24 months post-dose
Disease Control Rate (DCR)	Pre-dose up to approximately 24 months post-dose
Progression Free Survival (PFS)	Pre-dose up to approximately 24 months post-dose
Time to Tumor Progression (TTP)	Pre-dose up to approximately 24 months post-dose
Time to Response (TTR)	Pre-dose up to approximately 24 months post-dose
Time to Treatment Failure (TTF)	Pre-dose up to approximately 24 months post-dose
Overall Survival (OS)	Pre-dose up to approximately 24 months post-dose
1-year Progression Free Survival	Pre-dose up to approximately 24 months post-dose
1-year Survival	Pre-dose up to approximately 24 months post-dose
Number of Participants Experiencing Adverse Events (AE)	Pre-dose up to approximately 24 months post-dose
Number of Participants Experiencing Adverse Drug Reactions (ADR)	Pre-dose up to approximately 24 months post-dose
Number of Participants Experiencing Serious Adverse Events (SAE)	Pre-dose up to approximately 24 months post-dose
Number of Participants Experiencing Serious Adverse Reactions (SAR)	Pre-dose up to approximately 24 months post-dose
Objective Response Rate (ORR) by Investigator	Pre-dose up to approximately 24 months post-dose
Area Under The Curve (AUC) of TL938	Pre-dose up to 24 hours post-dose
Maximum Plasma Concentration (Cmax) of TL938	Pre-dose up to 24 hours post-dose
Minimum Plasma Concentration (Cmin) of TL938	Pre-dose up to 24 hours post-dose
Time to Peak Drug Concentration (Tmax) of TL938	Pre-dose up to 24 hours post-dose
TL938 half-life (T1/2)	Pre-dose up to 24 hours post-dose
Volume of Distribution (Vz/F) of TL938	Pre-dose up to 24 hours post-dose
Apparent Clearance (CL/f) of TL938	Pre-dose up to 24 hours post-dose

Collaborators and Investigators

• Sponsor: Suzhou Teligene Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: September 6, 2024
• First Submitted That Met QC Criteria: September 6, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: HER2; Oncology; Colorectal Cancer; TL938
• Additional Relevant MeSH Terms: Neoplasms by Site; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplasms; Colorectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Trastuzumab
• Other Study ID Numbers: TL-HER-202301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No