Immunotherapy with Thymalfasin for Advanced Colorectal Cancer

Efficacy and Safety Study of Thymalfasin in Combination with Targeted Immunotherapy (Regorafenib and Tislelizumab) in Patients with Advanced PMMR/MSS Colorectal Cancer Who Failed Standard of Care: a Multicenter, Open-label, Randomized, Controlled Clinical Study

This study is testing if adding a new drug called Thymalfasin to a standard treatment can help people with advanced colorectal cancer live longer without their disease getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Beijing Friendship Hospital (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy, prednisone, Tislelizumab
• Locations: 1 site (Beijing, China)
• Trial ID: NCT06829355 on ClinicalTrials.gov

What this trial studies

This Phase II clinical study evaluates the efficacy of a triple therapy regimen combining Thymalfasin, Regorafenib, and Tislelizumab against a double therapy regimen of Regorafenib and Tislelizumab in patients with advanced metastatic colorectal cancer. Participants will be randomly assigned to either treatment group and monitored for disease progression or intolerable side effects. The study aims to determine if the addition of Thymalfasin can improve progression-free survival compared to the standard double therapy. The trial will enroll a total of 52 subjects across multiple centers in Beijing.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with advanced or metastatic colorectal adenocarcinoma who have previously progressed on standard therapies.

Not a fit: Patients with significant liver metastases or those who have not undergone at least second-line systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve progression-free survival for patients with advanced colorectal cancer.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches, suggesting potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* Able to sign a written informed consent form (ICF) and able to understand and comply with the requirements of this study Male or female aged 18 to 75 Histologically or cytologically confirmed advanced or metastatic colorectal adenocarcinoma Mismatch repair (MMR) protein expression or microsatellite instability (MSI) testing showing pMMR/MSS ECOG score of 0 or 1 At least one measurable lesion per iRECIST Expected survival of ≥ 3 months Disease progression or intolerance after at least second-line standard systemic therapy

Normal major organ function and hematological parameters (within 14 days prior to randomization):

Hematology tests must meet the following criteria:

WBCs≥2.0×10\^9/L NEUT≥1.5×10\^9/L Hb≥90g/L (9.0g/dL); PLT ≥100×10\^9/L;

Biochemistry tests must meet the following criteria:

TBIL ≤ 1.5 × upper limit of normal (ULN); Without liver metastases, ALT or AST ≤ 3.0 ULN; with liver metastases, ALT or AST ≤ 5 ULN; Serum albumin level ≥ 30 g/L Serum Cr ≤ 1.5 ULN, with an endogenous creatinine clearance (CrCl) \> 40 mL/min (using Cockcroft-Gault formula) For females: CrCl =((140-Age）×Weight（kg）× 0.85)/(72 × Cr (mg/dL)) For males: CrCl =((140-Age）×Weight（kg）× 1.00)/(72 × Cr (mg/dL)) Urine protein \< 2+; if urine protein ≥ 2+, 24-hour urine protein must be \< 1 g Prothrombin time or activated partial thromboplastin time and international normalized ratio ≤ 1.5 × ULN Able to swallow and absorb oral medication Females of childbearing potential must use appropriate contraceptive methods during the study and for 6 months after the last dose of the study drug. For males, they should be surgically sterilized or agree to use appropriate contraceptive methods during the study and for 6 months after the last dose of the study drug.

Exclusion Criteria:

* 1\. Previous treatment with Regorafenib, PD-1, PD-L1, or CTLA-4 inhibitors, or any form of immunotherapy; 2. Treatment with related drugs or medical technology affecting immunity within 6 months prior to the first dose of the study drug (including but not limited to: thymopentin, interferon, tumor vaccines, CAR-T therapy, etc.); 3. Receiving any study drug, radiotherapy, or major surgery within 28 days prior to the first dose of the study drug; 4. Receiving any anti-tumor treatment (chemotherapy, targeted therapy, etc.) within 3 weeks prior to the first dose of the study drug; 5. Presence of symptomatic central nervous system (CNS) metastases or CNS metastases requiring local CNS-directed therapy (such as radiotherapy or surgery). Exceptions include those previously treated and stable for ≥ 2 months and who have stopped systemic treatment for more than 4 weeks prior to the first dose of the study drug; 6. Known allergy or intolerance to any of the study drugs or their components; 7. Pregnant or lactating females; 8. History of other malignant tumors within the past 5 years (excluding carcinoma in situ or basal cell or squamous cell skin cancer; subjects with other malignant tumors who have been cured for at least 5 years are eligible); 9. Symptomatic congestive heart failure (NYHA Class II-IV), symptomatic or uncontrolled arrhythmias; 10. Poorly controlled hypertension, defined as systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite best medical treatment; 11. Unstable angina (angina symptoms at rest), new onset angina (within the past 3 months), or myocardial infarction within 6 months prior to the first dose of the study drug; 12. Major thrombotic or bleeding events within 6 months prior to randomization (including hemoptysis, gastrointestinal bleeding, hematemesis, central nervous system (CNS) bleeding, severe epistaxis or vaginal bleeding, cerebral infarction, transient ischemic attack, or uncontrolled coronary heart disease). Or requiring lifelong oral anticoagulant therapy; 13. With active, known, or suspected autoimmune diseases; 14. Receiving immunosuppressive agents within 4 weeks prior to the first dose of the study drug, excluding topical glucocorticoids or physiological doses of systemic glucocorticoids administered by nasal, inhalation, or other routes (i.e., no more than 10 mg prednisolone per day or equivalent dosage of other glucocorticoids); 15. Diagnosed with immunodeficiency or on chronic systemic steroid therapy (at a dose in excess of 10 mg prednisone equivalent per day) or any other form of immunosuppressive therapy; 16. History of interstitial lung disease; 17. Active tuberculosis requiring anti-tuberculosis treatment or treatment for tuberculosis within 1 year prior to the first dose of the study drug; 18. Acute or chronic active hepatitis B or hepatitis C; 19. Known history of human immunodeficiency virus (HIV) or syphilis infection; 20. Other active or severe infections requiring systemic antibacterial, antifungal, or antiviral treatment within 4 weeks prior to the first dose of the study drug; 21. Unresolved clinical toxicity ≥ Grade 2 (NCI-CTCAE, v5.0) due to prior anti-tumor treatment, excluding alopecia or non-clinically significant laboratory abnormalities; 22. Intestinal obstruction, gastrointestinal perforation, Crohn's disease, ulcerative colitis, abdominal abscess, chronic diarrhea, or fistula disease within 6 months prior to enrollment; 23. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or more severe cirrhosis; 24. Vaccination with live vaccines within 30 days prior to planned initiation of the study drug (seasonal influenza vaccines without live virus are permitted); 25. History of alcohol abuse or drug abuse; 26. Other acute or chronic diseases, psychiatric disorders, or laboratory abnormalities that the investigator believes would make the use of the study drug unfavorable or affect the interpretation of AEs, or, in the investigator's judgment, would result in inadequate compliance during the study period.

Where this trial is running

Beijing, China

• Beijing Friendship Hospital, Capital Medical University — Beijing, China, China (Recruiting)

Study contacts

• Principal investigator: Zhongtao Zhang, Professor — Beijing Friendship Hospital
• Study coordinator: Zhigang Bai, MD

Conditions MCRC; Thymalfasin; Regorafenib; Tislelizumab; mCRC; Combination; Immunotherapy; RCT