A Phase II Clinical Study of the Efficacy and Safety of Tislelizumab Combined With Fruquintinib and Chidamide in the Treatment of Unresectable or Advanced Microsatellite Stabilized (MSS/pMMR) Colorectal Cancer With Liver Metastases

NCT06218888 | Not Yet Recruiting Phase 2

• 1 other identifier: TFC
• Study Type: interventional
• Target: 17
• Locations: 0 countries
• Sites: N/A

Brief Summary

To explore the Efficacy and Safety of Tislelizumab combined with fruquintinib and Chidamide in the treatment of unresectable or advanced microsatellite stabilized (MSS/pMMR) colorectal cancer with liver metastases

Conditions

Colo-rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate（ORR）

  The percentage of subjects whose therapeutic effect evaluation is complete response (CR) or partial response (PR) according to RECIST 1.1.

  Around 2 years

Secondary Outcomes (2)

• Progression-Free Survival (PFS)

  Around 2 years

• Disease Control Rate (DCR)

  Around 2 years

Study Arms (1)

Tislelizumab combined with fruquintinib and Chidamide

EXPERIMENTAL

The treatment option for the chidamide + tislelizumab +fruquibtinib is 200 mg of tislelizumab IV Drip Q3W, 30 mg of chidamide PO BIW, and fruquibtinib 3mg PO Q3W until loss of clinical benefit or development of intolerable toxicity

Drug: Tislelizumab; Drug: Fruquintinib; Drug: Chidamide

Interventions

Tislelizumab DRUG

Tislelizumab 200mg，D1, Q3W

Tislelizumab combined with fruquintinib and Chidamide

Fruquintinib DRUG

Fruquintinib 3mg ,D1-D14, Q3W

Tislelizumab combined with fruquintinib and Chidamide

Chidamide DRUG

Chidamide 30mg

Tislelizumab combined with fruquintinib and Chidamide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years old and ≤ 75 years old.
• Expected survival time ≥ 18 weeks.
• Diagnosis of pMMR confirmed by PCR for microsatellite stability (MSS) or low microsatellite instability (MSI-L), or by immunohistochemistry for DNA mismatch repair (MMR) proteins, including MLH1, MSH2, MSH6 and PMS2 protein expression, which result in no protein deletion.
• Subjects with histologically and/or cytologically confirmed locally advanced unresectable or metastatic colorectal adenocarcinoma with liver metastasis (excluding adenosquamous carcinoma mixed with other pathological types).
• ECOG PS score is in the range of 0\~1.
• Failure of previous treatment with fluorouracil, oxaliplatin, and irinotecan based chemotherapy, with imaging evidence (such as CT scans) or clinical evidence (such as cytological reports of new ascites or pleural effusion) demonstrating disease progression during or after treatment, or discontinuation of treatment due to toxicity intolerance.
• Subjects having adequate organ and bone marrow functions with laboratory test values within 7 days prior to enrollment meeting the following requirements, as follows:
• Blood routine: absolute neutrophil count (ANC) ≥ 1.5×109/L; platelet count (PLT) ≥ 100×109/L; hemoglobin level (HGB) ≥ 9.0 g/dL.
• Liver function: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN in subjects without liver metastases, and ALT and AST ≤ 5.0 × ULN in subjects with liver metastases; serum albumin ≥ 25 g/L.
• Renal function: serum creatinine (Cr) ≤ 1.5 x ULN. 4) Patients with routine urine results showing urine protein \<2+ or routine urine testing showing urine protein ≥ 2+ at baseline should undergo 24-hour urine collection and 24-hour urine protein quantification \< 1 g.
• \) Coagulation function: international normalized ratio (INR) ≤ 1.5×ULN and activated partial thromboplastin time (APTT) ≤ 1.5×ULN.

You may not qualify if:

• Prior exposure to any anti-PD-1 antibody, anti-PD-L1 antibody, HDAC inhibitor, or irinotecan.
• Receiving any investigational drug within 4 weeks prior to the first dose of the study drug.
• Concurrent participation in another interventional clinical study, except in an observational (non-interventional) clinical study or in the follow-up phase of an interventional study.
• Receiving the last dose of antitumor therapy (chemotherapy, targeted therapy, tumor immunotherapy, or tumor embolization) within 3 weeks prior to the first dose.
• Receiving radiotherapy within 4 weeks prior to the first dose.
• Patients who have received radiotherapy more than 4 weeks prior to the first dose with any radiotherapy-related toxic reactions, such as radiation pneumonia, radiation hepatitis, radiation enteritis, including clinical symptoms only, or requiring glucocorticoid therapy.
• Use of immunosuppressive drugs within 4 weeks prior to the first dose, excluding topical glucocorticoids by nasal spray, inhalation or other routes or physiological doses of systemic glucocorticoids (i.e., no more than 10 mg/day prednisone or equivalent doses of other glucocorticoids).
• Receiving live attenuated vaccine within 4 weeks prior to the first dose or planning to receive during the study period.
• Major surgical procedure (craniotomy, thoracotomy or open heart surgery) or unhealed wound, ulcer or fracture within 4 weeks prior to the first dose.
• Presence of toxicity (excluding alopecia, non-clinically significant and asymptomatic laboratory abnormalities) from prior antineoplastic therapy not recovered to ≤ grade 1 by NCI common terminology criteriafor adverse events (CTCAE) Version 5.0 (NCI CTCAE Version 5.0) prior to the first dose.
• Known presence of symptomatic CNS metastases and/or carcinomatous meningitis. Subjects with prior treatment for brain metastases may participate in the study provided that the brain metastases have remained stable for at least 4 weeks prior to the first dose of study treatment; and that neurological symptoms have recovered to ≤ grade 1 by NCI CTCAE version 5.0.
• Active autoimmune disease requiring systemic therapy (e.g., use of disease-relieving drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Alternative therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) are allowed. A known history of primary immunodeficiency. For patients with only positive autoimmune antibodies, the presence of autoimmune diseases should be confirmed at the discretion of the investigator.
• Patients who are known to have active tuberculosis and are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year prior to the first dose.
• Known to have interstitial lung disease requiring steroid hormone therapy.
• Known to have acute or chronic active hepatitis B (HBsAg positive and HBV DNA ≥ 200 IU/mL or ≥ 103 copies/mL) or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive).

Sponsors & Collaborators

• Fujian Cancer Hospital: lead

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

tislelizumab; HMPL-013; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Central Study Contacts

Li hui, bachelor

CONTACT

13600855801; Lihui7701@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2024
• First Posted: January 23, 2024
• Study Start: June 1, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 23, 2024

Record last verified: 2024-01