Tislelizumab Plus Cetuximab and Irinotecan vs Third-line Standard-of-care in Refractory mCRC

NCT05278351 | Unknown Phase 2

• 1 other identifier: TEC2
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, randomized, controlled, phase II study to evaluate the efficacy and safety of tislelizumab combined with cetuximab and irinotecan（group A） compared to third-line regimens selected by researchers（group B） in the treatment of Ras wild-type recurrent and refractory metastatic colorectal cancer. This study will include Ras wild-type colorectal cancer that failed at least second-line treatment inthe past, including chemotherapy (oxaliplatin, irinotecan, fluorouracil) with or without targeted drugs (cetuximab, bevacizumab). 87 patients will be randomly assigned to group A and group B according to 2:1. The enrollment time is expected to be 12 months and the follow-up is expected to be 24 months.

Conditions

Colorectal Neoplasms Malignant

Outcome Measures

Primary Outcomes (1)

• Progression free survival time (PFS)

  time from the start of medication to the initial progression of the disease

  24 months after the last subject participating in

Secondary Outcomes (3)

• Objective response rate (ORR)

  24 months after the last subject participating in

• Disease control rate (DCR)

  24 months after the last subject participating in

• Overall survival (OS)

  36 months after the last subject participating in

Study Arms (2)

A

EXPERIMENTAL

Tislelizumab 200mg, D1, D15, intravenous drip, Q4W and Cetuximab 500mg/m2, D1, D15, intravenous drip, Q4W and Irinotecan 180mg/m2, D1, D15, intravenous drip, Q4W

Drug: Tislelizumab Combined With Cetuximab and Irinotecan

B

ACTIVE COMPARATOR

Fruquinitinib 5mg QD D1-21, oral, Q4W or Regorafenib 160mg QD D1-21 oral, Q4W or Trifluridine Tipiracil Tablets 35mg/m2 BID D1-D5, D8-D12 oral, Q4W

Drug: Third-line regimens

Interventions

Tislelizumab Combined With Cetuximab and Irinotecan DRUG

Tislelizumab (an anti-PD-1 monoclonal antibody) Cetuximab (monoclonal antibody against EGFR) Irinotecan

Also known as: TEC

A

Third-line regimens DRUG

Trifluridinetipiracil or Regorafenib or Fruquintinib

B

Eligibility Criteria

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

You may qualify if:

• Age≥18years；
• The ECOG PS score was≤1;
• Ras wild-type colorectal cancer diagnosed by histology and/or cytology has metastasis or recurrence that cannot be cured by surgery;
• Have received at least second-line systemic anti-tumor treatments for mCRC and failed, in which chemotherapy drugs can include fluorouracil, oxaliplatin or irinotecan; with or without targeted drugs, such as cetuximab or bevacizumab;
• At least one measurable lesion defined according to RECIST version 1.1;
• Patients with fertility must be willing to take efficient contraceptive measures during the study period and ≥ 120 days after the last administration of drugs; female patients have negative urine or serum pregnancy test results ≤ 7 days before the first administration of the study drugs;
• Fully understand and voluntarily sign the informed consent form;
• Organ function is good ≤ 7 days before randomization, as shown in the following:
• a.Blood transfusion or growth factor support within 2 weeks before enrollment are not allowed to meet the enrollment criteria: i. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9 / L; ii.Platelet count≥ 75 × 10\^9 / L; iii.Hemoglobin≥9g/dL or 90g / L or 5.6mmol/l; b. Serum total bilirubin ≤1.5 times the upper limit of normal value(ULN); c. Aspartate aminotransferase (AST) and alanine aminotransferase(ALT) ≤2.5 times ULN, or ALT and/or AST ≤5 times ULN in patients with liver metastasis; d. Serum creatinine ≤ 1.5 times the upper limit of normal value(ULN); e. Partial prothrombin time (APTT) or prothrombin time (PT) ≤1.5 times ULN; f. Albumin ≥30g / L;

You may not qualify if:

• Any previous histological or hematological ctDNA test showed mismatch repair gene deletion (dMMR), microsatellite instability (MSI-H), BRAF mutant patients;
• Previous immunotherapy, including anti-PD-1, anti-PD-L1, anti-CTLA-4 or any cellular immunotherapy;
• There is active leptomeningeal disease or brain metastasis that is not well controlled;
• History of active autoimmune diseases or autoimmune diseases that may recur. Note: Patients with the following diseases are not excluded and can be further screened:
• Well controlled type I diabetes mellitus
• Hypothyroidism (controlled by hormone replacement therapy only)
• Well controlled celiac disease
• Skin diseases that do not require systematic treatment (e.g. vitiligo, psoriasis, hair loss)
• Any other disease that is not expected to recur without external triggers
• Any active malignant tumor ≤ 5 years before the first administration of the study drug, except the specific cancer studied in this trial and any locally recurrent cancer that has received radical treatment (such as excised basal cell or squamous cell skin cancer, cervical or breast cancer in situ);
• Any case requiring systemic treatment with corticosteroids (prednisone or equivalent \> 10 mg / day) or other immunosuppressive drugs ≤ 14 days before the first administration of the study drug. Note: patients who have currently or previously used any of the following steroid regimens are not excluded:
• Adrenal replacement steroids (prednisone or equivalent ≤ 10 mg / day)
• Inhaled corticosteroids with very low local, eye, intra-articular, intranasal or systemic absorption
• Short term (≤ 7 days) prophylactic use of corticosteroids (e.g. for the treatment of contrast medium allergy) or for the treatment of non autoimmune diseases (e.g. delayed type hypersensitivity caused by contact allergens)
• There was uncontrolled diabetes, or over 3 grade hypoalbuminemia or \>1 grade potassium, sodium or calcium abnormalities within 14 days before the first drug administration,

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Cetuximab; Irinotecan

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Oncology Department

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: March 14, 2022
• Study Start: July 13, 2022
• Primary Completion: April 1, 2024
• Study Completion: December 1, 2025
• Last Updated: March 31, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)