A Clinical Study of BioTTT001 in Combination With Toripalimab and Regorafenib in Patients With Colorectal Cancer

A Clinical Study to Evaluate the Safety and Efficacy of Recombinant Human nsIL12 Oncolytic Adenovirus Injection (BioTTT001) in Combination With Toripalimab and Regorafenib in Patients With Liver Metastases From Colorectal Cancer

This is a phase I, open-label clinical study of BioTTT001 in combination with Toraplizumab and Regorafenib in patients with liver metastases from colorectal cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: regorafenib; Biological: BioTTT001 hepatic artery infusion; Drug: toripalimab

Detailed Description

This study includes a dose escalation phase and a dose expansion phase. The dose escalation phase will adopt a 3+3 design. Subjects were first treated with BioTTT001 monotherapy (hepatic artery infusion, administered on D1 and D8 for a total of two doses) after enrollment. If the subject does not develop dose-limiting toxicity (DLT) in the monotherapy stage and is judged to be safe and tolerable by the investigator, the subject will enter the treatment phase of BioTTT001 in combination with toripalimab and regorafenib 2 weeks after the first dose of BioTTT001 ( toripalimab 160mg iv. D1 and D15 , BioTTT001 5×10^9 viral particle (VP)/5×10^10 VP/1×10^11 VP hepatic arterial infusion (HAI.) D2 and D16 , regorafenib 80 mg Po. D1-D21; 4 weeks per cycle). In the dose expansion phase, different dose groups can be expanded, and the total number of enrolled subjects is expected to be 23~48 for further safety, tolerability, pharmacokinetics and preliminary efficacy evaluation.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Shuhui Song, bachelor; Phone Number: 024 15004240769; Email: 593900927@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age range from 18 to 70 years old (including the threshold), no gender restrictions;
2. 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;
3. At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
4. WBC≥3.0×10^9/L; ANC≥1.5×10^9/L (without cytokine therapy within one week before the screening ); Hb≥90g/L(without blood transfusion within one week before the screening);PLT≥90×10^9/L(without Platelet transfusion or thrombopoietin (TPO) within one week before the screening)；ALT and AST≤5×ULN；Cr≤1.5×ULN or CCr>50mL/min; TBIL≤1.5×ULN; APTT≤1.5×ULN and INR/PT≤1.5×ULN；
5. ECOG 0~2；
6. Expected survival ≥ 3 months;
7. Consent to contraception；
8. Understand and voluntarily sign a written ICF and be willing to comply with all trial requirements.

Exclusion Criteria:

1. Known allergy to the investigational drug or its components;
2. Previous treatment with other adenovirus drugs;
3. Patients with active autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, etc.), except type 1 diabetes, hypothyroidism that only needs hormone replacement therapy, and skin diseases that do not need systemic treatment (such as vitiligo, psoriasis or alopecia);
4. Received treatment with nitrosourea or mitomycin C within 6 weeks before the first dose of BioTTT001; received oral fluorouracil and small molecule targeted drug therapy within 2 weeks or 5 half-lives of the drug within 2 weeks before the first dose of BioTTT001; received traditional Chinese medicine therapy with anti-tumor indications within 2 weeks before the first dose of BioTTT001; received chemotherapy, radiotherapy, biological therapy other than the drugs mentioned above within 28 days before the first dose of BioTTT001；
5. Patients who have not recovered from the adverse reactions of previous treatments (the treatment-related toxicity ≤ grade 2, except for alopecia, pigmentation or other tolerable events judged by the investigator ).
6. History of other malignancies (except cured basal cell skin cancer, cervical carcinoma in situ, Papillary carcinoma of thyroid gland, low-risk GIST etc.) within 5 years before study drug administration;
7. Patients who have undergone any major surgery (except needle biopsy, etc.) or severe trauma within 4 weeks before the first dose of BioTTT001;
8. Patients who have been treated with high-dose systemic corticosteroids (prednisone > 10 mg/day or equivalent doses) or other immunosuppressants within 2 weeks before the first dose of BioTTT001;
9. NYHA≥grade 3; LVEF<50%; male QTc>450 mms, female QTc>470 mms;
10. Patients with active tuberculosis or drug-induced interstitial lung disease；
11. Patients with active infection requiring systemic anti-infective therapy;
12. In a state of immunosuppression, such as severe combined immunodeficiency disease or concurrent opportunistic infections;
13. HBsAg positive, and blood HBV DNA≥100 IU/mL; anti-HCV positive; HIV positive; active syphilis;
14. Patients with pleural effusion and ascites with clinical symptoms that require repeated drainage;
15. Patients with central nervous system metastases or meningeal metastases with clinical symptoms;
16. Patients with contraindications to hepatic arterial perfusion therapy;
17. Pregnant or lactating women;
18. Patients with prior organ transplants;
19. Other reasons judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination therapy with BioTTT001 hepatic artery infusion , Regorafenib and Toripalimab; This study includes a dose escalation phase and a dose expansion phase. The dose escalation phase will adopt a 3+3 design. Subjects were first treated with BioTTT001 monotherapy (hepatic artery infusion, administered on D1 and D8 for a total of two doses) after enrollment. If the subject does not develop dose-limiting toxicity (DLT) in the monotherapy stage and is judged to be safe and tolerable by the investigator, the subject will enter the treatment phase of BioTTT001 in combination with toripalimab and regorafenib 2 weeks after the first dose of BioTTT001 ( toripalimab 160mg iv. D1 and D15 , BioTTT001 5×10^9 viral particle (VP)/5×10^10 VP/1×10^11 VP hepatic arterial infusion (HAI.) D2 and D16 , regorafenib 80 mg Po. D1-D21; 4 weeks per cycle). In the dose expansion phase, different dose groups can be expanded, and the total number of enrolled subjects is expected to be 23~48 for further safety, tolerability, pharmacokinetics and preliminary efficacy evaluation.

Drug: regorafenib; BioTTT001 in combination with toripalimab and regorafenib period: regorafenib 80 mg oral administration, D1-D21, 4 weeks per cycle.; Biological: BioTTT001 hepatic artery infusion; BioTTT001 monotherapy period: BioTTT001 5×10^9 VP/5×10^10VP/1×10^11 VP hepatic artery infusion, administered on D1 and D8, for a total of two doses after enrollment. BioTTT001 in combination with toripalimab and regorafenib period: BioTTT001 5×10^9 VP/5×10^10VP/1×10^11 VP hepatic artery infusion, D2 and D16, 4 weeks per cycle.; Drug: toripalimab; BioTTT001 in combination with toripalimab and regorafenib period: toripalimab 160mg intravenous D1 and D15, 4 weeks per cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	The incidence and severity of all types of adverse events evaluated based on NCI-CTCAE V5.0 assessment.	From the enrollment to 28 days after the end-of-trial visit (i.e. end of treatment or early termination visit)
MTD	Maximum tolerated dose (MTD)	42 days within the first dose of BioTTT001 injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival(OS)	The time from the start of treatment to death for any cause	Every 3 months until consent withdraw, death, withdrawal study, or loss of follow-up, up to 100 weeks
Progression-free survival (PFS)	The time from the start of treatment to progress disease or death for any cause	At C1D28 of the combination therapy phase for the first time, and then every 8 weeks until disease progression, consent withdraw, death or end of study during the combination therapy phase, up to 100 weeks.
Objective response rate (ORR)	Objective response rate (ORR) as assessed by the investigators	Imaging will be performed at C1D28 of the combination therapy phase for the first time, and then every 8 weeks during the combination therapy phase.
Plasma adenovirus (ADV) copies	Pharmacokinetic Study (PK): Copies of ADV in plasma at various sampling points.	8 days within the first BioTTT001 injection dose
ADV copies in various sites	Viral Shedding Analysis: Copies of ADV in swabs of rectal swabs, throat swabs, and urine samples at various sampling points.	8 days within the first BioTTT001 injection dose
Serum IL-12 level	Expression levels of IL-12 at various sampling points in serum.	8 days within the first BioTTT001 injection dose
Serum neutralizing antibody level	Immunogenicity assessment through adenovirus neutralizing antibody detection.	8 days within the first BioTTT001 injection dose

Collaborators and Investigators

• Sponsor: China Medical University, China
• Collaborators: Beijing Bio-Targeting Therapeutics Technology Co., Ltd
• Investigators: Principal Investigator: Zhenning Wang, MD, The First Affiliated Hospital of China Medical Univeristy; Principal Investigator: Funan Liu, MD, The First Affiliated Hospital of China Medical Univeristy

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: February 22, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 4, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: liver metastasis; oncolytic virus; hepatic artery infusion; colorectal Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; toripalimab; regorafenib
• Other Study ID Numbers: BJCT-CMU1H-02

Drug and device information, study documents

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