A Clinical Study of T3011 in Combination With Toripalimab and Regorafenib in Patients With Colorectal Cancer

NCT06283303 | Not Yet Recruiting Phase 1

• 1 other identifier: MVR-T3011-HAI-01
• Study Type: interventional
• Target: 8
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase I, open-label clinical study of T3011 in combination with Toraplizumab and Regorafenib in patients with liver metastases from colorectal cancer.

Conditions

Colorectal Cancer Metastatic

Keywords

oncolytic virus; colorectal Cancer; liver metastasis; hepatic artery infusion

Outcome Measures

Primary Outcomes (1)

• Treatment Emergent Adverse Event（TEAE）

  An adverse event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state.

  Complete records until 30 days after the end-of-trial visit (i.e. end of treatment or early termination visit)

Secondary Outcomes (3)

• Objective response rate (ORR)

  Imaging was performed after completion of the introductory period, i.e. at week 4, and tumour assessment was performed every 8 weeks during the subsequent combined treatment period，assessed up to 100 months

• Overall survival (OS)

  Every 3 months until consent withdraw, death, withdrawal study, or loss of follow-up, assessed up to 100 months

• Progression-free survival (PFS)

  Every 8 weeks until disease progression, consent withdraw, death or end of study, assessed up to 100 months

Study Arms (1)

Combination therapy with T3011 hepatic artery infusion , Regorafenib and Toripalimab

EXPERIMENTAL

The study was divided into two dose groups, T3011 3×10\^8 plaque forming unit(PFU)/time (HAI) and T3011 1×10\^9 PFU/time (HAI), with a 3+3 dose escalation design. After the completion of the lead-in period, the patient entered the combination therapy period（combination therapy with T3011 hepatic artery infusion , Regorafenib and Toripalimab）,and the dosage of T3011 was determined according to the safety observation results of the lead-in period, the dose of toripalimab was 80mg intravenously, and regorafenib was 80mg orally once a day.

Biological: T3011 hepatic artery infusion; Drug: toripalimab; Drug: regorafenib

Interventions

T3011 hepatic artery infusion BIOLOGICAL

The study was divided into two dose groups, T3011 3×10\^8 PFU/time (HAI) and T3011 1×10\^9 PFU/time (HAI), with a 3+3 dose escalation design. After the completion of the lead-in period, the patient entered the combination therapy period（combination therapy with T3011 hepatic artery infusion , Regorafenib and Toripalimab）,and the dosage of T3011 was determined according to the safety observation results of the lead-in period, the dose of toripalimab was 80mg intravenously, and regorafenib was 80mg orally once a day.

Combination therapy with T3011 hepatic artery infusion , Regorafenib and Toripalimab

toripalimab DRUG

The combination therapy period: toripalimab, 80mg intravenous ,D2 and D16, 4 weeks per cycle

Combination therapy with T3011 hepatic artery infusion , Regorafenib and Toripalimab

regorafenib DRUG

The combination therapy period: regorafenib ,80mg orally once a day, D1-D21,4 weeks per cycle

Combination therapy with T3011 hepatic artery infusion , Regorafenib and Toripalimab

Eligibility Criteria

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

You may qualify if:

• Men or women aged ≥18 years at the time of signing the Informed Consent Form (ICF);
• Patients with a definitive histopathological or cytological diagnosis of colorectal cancer with hepatic metastases who have received and failed at least second-line standard therapy in the past, or who have been assessed by the investigator to be unsuitable for standard therapy;
• Patients with at least one measurable lesion (as defined by RECIST v1.1) that has not been previously treated with radiotherapy (unless definite progression of the lesion has occurred after radiotherapy);
• Eastern Cooperative Oncology Group(ECOG) score 0 or 1;
• Expected survival ≥ 12 weeks;
• For female subjects with childbearing potential, a negative serum pregnancy test within 7 days prior to the first dose of study drug; Acceptance of using medically accepted and effective contraception for at least 6 months after signing the ICF and until the last dose of study drug;
• Male subjects with childbearing potential agree to use medically accepted and effective contraception from the date of signing the ICF to the date of at least 6 months after the last dose; in addition, the male subject must agree that he will not donate sperm during this period;
• Understand and voluntarily sign a written ICF and be willing to comply with all trial requirements.

You may not qualify if:

• Patients allergic to the study drug (including its components) or other similar products;
• Patients who have been treated with oncolytic virus therapy, interleukin-12 (IL-12) in combination with anti PD-1/ PD-L1;
• Patients who have not recovered from the adverse reactions of previous treatments (the treatment-related toxicity ≤ grade 2, except for alopecia, fatigue or other tolerable events judged by the investigator);
• Patients with brain metastases that have progressed within 3 months prior to study drug administration (brain metastases that have stabilised within 3 months may be included);
• History of other malignancies (except cured basal cell skin cancer, cervical carcinoma in situ, papillary thyroid cancer, etc.) within 5 years prior to study drug administration;
• Patients who received any antineoplastic drug (including but not limited to chemotherapy, biologics, herbal preparations, etc.) within 4 weeks or 5 half-lives (whichever is shorter) prior to study drug administration;
• Severe hepatic dysfunction (Child Pugh class C), or significant jaundice, hepatic encephalopathy, refractory pleural effusion, or hepatorenal syndrome; Coagulation: international normalized ratio (INR) or Prothrombin time (PT) \> 1.5 x Upper limits of normal(ULN) ; activated partial thromboplastin time (aPTT)\> 1.5 x ULN; Current comorbidity with active hepatitis: persistent or active hepatitis B (i.e. HBsAg positive or hepatitis B virus (HBV) DNA ≥ upper limit of detection), hepatitis C (HCV RNA ≥ upper limit of detection)\] or other hepatitis; Haematology: white blood cell count (WBC) \< 3.0 x 10\^9/L; platelets \< 75 x 10\^9/L; haemoglobin \< 80g/L; Renal function: serum creatinine \>1.5 ULN or creatinine clearance \<60 mL/min (Cockcroft-Gault formula calculation)
• Serious or uncontrollable cardiac disease requiring treatment, congestive heart failure classified as grade 3 or 4 by the New York Heart Association (NYHA), unstable angina not controlled by medication, history of myocardial infarction within 6 months prior to enrolment, serious arrhythmia requiring medication (except atrial fibrillation or paroxysmal supraventricular tachycardia); History of arterial thromboembolic event, venous thromboembolic event of grade ≥3 as defined in NCI CTCAE 5.0, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to randomisation; Current major vascular disease such as aortic aneurysm, aortic coarctation aneurysm, etc. that may be life-threatening or require surgery within 6 months;
• Previous immunotherapy (including but not limited to PD-1/PD-L1) with immune-related pneumonitis or ≥ grade 3 other immune-related adverse reactions; Current active immune disease requiring systemic treatment with immunosuppressive agents (excluding autoimmune diseases such as vitiligo that do not require intervention, or hypothyroidism that only needs hormone replacement therapy), or immune disease requiring systemic treatment with immunosuppressive agents (e.g., systemic lupus erythematosus) that is likely to recur; Patients with other diseases currently requiring systemic immunosuppressive therapy;
• HIV Positive; Patients who are currently in the midst of an episode of orofacial herpes; Clinically significant infection or infection treated with intravenous antibiotics within 4 weeks prior to dosing;
• Inability to swallow, malabsorption syndrome, or uncontrollable nausea, vomiting, diarrhoea or other gastrointestinal disorders that would seriously interfere with drug administration and absorption;
• Patients who need anti-herpes simplex virus medications (including, but not limited to, acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir, etc.) for the duration of the study, with the exception of topical applications;
• History of seizures within 12 months prior to study drug administration;
• Patients with the history of drug use or a history of substance abuse (including alcohol) within one year prior to signing the ICF;
• Pregnant or lactating women;

Sponsors & Collaborators

• China Medical University, China: lead
• Immvira Co., Limited: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

toripalimab; regorafenib

Condition Hierarchy (Ancestors)

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

Study Officials

• Zhenning Wang, MD

  The First Affiliated Hospital of China Medical Univeristy

  PRINCIPAL INVESTIGATOR

• Funan Liu, MD

  The First Affiliated Hospital of China Medical Univeristy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shuhui Song, bachelor

CONTACT

15004240769; 593900927@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: February 21, 2024
• First Posted: February 28, 2024
• Study Start: April 2, 2024
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: February 29, 2024

Record last verified: 2024-02