A Clinical Study of BioTTT001 in Combination With SOX and Toripalimab in Patients With Gastric Cancer

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

This is a phase I, single arm, open-label clinical study of BioTTT001 in combination with SOX and Toraplizumab in patients with peritoneal metastases from gastric cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer, Metastatic
• Intervention / Treatment: Biological: BioTTT001 intraperitoneal infusion; Drug: SOX regimen; Drug: toripalimab

Detailed Description

This study intends to enroll Her2-negative subjects with first-line treatment of peritoneal metastasis from gastric cancer. Subjects will be treated with BioTTT001 intraperitoneal perfusion combined with SOX and toripalimab after completing the screening period, and the subjects will first receive BioTTT001 monotherapy treatment with BioTTT001 1×10^10 viral particle (VP) intraperitoneal perfusion (P.I.), D1 and D3, and enter the combination therapy stage 7 days (±1d) after the first dose of BioTTT001.Subjects will be treated with the regimen as follows: BioTTT001 injection, 1×10^10 VP P.I., D1；toripalimab 160mg intravenous (i.v.), D1; Oxaliplatin 130mg/m^2 i.v. , D1 ; Tegafur 40~60mg Bis in die（b.i.d.） Peroral（p.o.）D1~D14; 3 weeks per cycle.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

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. Male or female, age≥ 18 years；
2. Patients with a diagnosis of gastric cancer by histopathology or cytology, accompanied by peritoneal metastasis, without systemic therapy, or for patients who have received neoadjuvant/adjuvant chemotherapy before, the time from last treatment to disease recurrence > 6 months;
3. Tumor Her2 negative (IHC 0/1＋ or IHC 2＋ and FISH-).
4. At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors （RECIST) 1.1;
5. WBC≥3.0×10^9 /L; ANC≥1.5×10^9 /L; HB≥90 g/L; PLT≥75×10^9 /L;
6. ALT and AST≤3×ULN (≤5×ULN with liver metastasis); ALB≥20g/L; Cr≤1.5×ULN or CCr>50 mL/min; TBIL≤1.5×ULN; APTT≤1.5×ULN and INR or PT≤1.5×ULN (without anticoagulation therapy)
7. LVEF≥50%; male QTc≤450 mms, female QTc≤470 mms;
8. ECOG 0~1；
9. Expected survival ≥ 3 months;
10. Consent to contraception；
11. Understand and voluntarily sign a written ICF and be willing to comply with all trial requirements.

Exclusion Criteria:

1. History of other malignancies (except cured basal cell skin cancer, cervical carcinoma in situ etc.) within 5 years before study drug administration;
2. Patients with central nervous system metastases with clinical symptoms;
3. 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;
4. Previous treatment with other adenovirus drugs within 28 days before the first dose of BioTTT001;
5. Patients who have undergone any major surgery (except needle biopsy, etc.) or severe trauma within 14 days before the first dose of BioTTT001;
6. Patients who have not recovered from the adverse reactions of previous treatments (the treatment-related toxicity ≤ grade 2, except for alopecia );
7. Patients with primary immunodeficiency;
8. 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);
9. Patients with active infection requiring systemic anti-infective therapy;
10. HBsAg positive, and blood HBV DNA≥100 IU/mL; anti-HCV positive; HIV positive; active syphilis;
11. Patients with active tuberculosis or drug-induced interstitial lung disease；
12. Patients with active inflammatory bowel disease ；
13. NYHA≥ grade 3；
14. Known allergy to the investigational drug or its components;
15. Patients with prior organ transplants;
16. Pregnant or lactating women;
17. 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 intraperitoneal infusion , SOX and Toripalimab; This study intends to enroll Her2-negative subjects with first-line treatment of peritoneal metastasis from gastric cancer. Subjects will be treated with BioTTT001 intraperitoneal perfusion combined with SOX and toripalimab after completing the screening period, and the subjects will first receive BioTTT001 monotherapy treatment with BioTTT001 1×10^10 VP intraperitoneal perfusion (P.I.), D1 and D3, and enter the combination therapy stage 7 days (±1d) after the first dose of BioTTT001.Subjects will be treated with the regimen as follows: BioTTT001 injection, 1×10^10 VP P.I., D1；toripalimab 160mg intravenous (i.v.), D1; Oxaliplatin 130mg/m^2 i.v. , D1 ; Tegafur 40~60mg Bis in die（b.i.d.） Peroral（p.o.）D1~D14; 3 weeks per cycle.

Biological: BioTTT001 intraperitoneal infusion; Monotherapy lead-in phase: BioTTT01 1×10^10 VP, i.p., D1 and D3; Combination therapy phase: BioTTT01 1×10^10 VP, i.p., D1 and D3, 3 weeks per cycle; Drug: SOX regimen; Combination therapy phase: Oxaliplatin 130 mg，i.v., D1 and D3, 3 weeks per cycle; Tegafur 40~60mg b.i.d. p.o. D1~D14; 3 weeks per cycle; Drug: toripalimab; Combination therapy phase: toripalimab 160mg i.v. D1, 3 weeks per cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Objective response rate (ORR) as assessed by the investigators	Imaging was performed every 6 weeks during the combination therapy phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	The time from the start of treatment to progress disease or death for any cause	Every 6 weeks until disease progression, consent withdraw, death or end of study during the combination therapy phase, up to 100 weeks.
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

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): April 2, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

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 (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: oncolytic virus; gastric cancer; peritoneal metastases; IL-12
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: BJCT-CMU1H-01

Drug and device information, study documents

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