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

Official title

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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Objective response rate (ORR) [Time frame: Imaging was performed every 6 weeks during the combination therapy phase]

Secondary outcome measures (2)

• Progression-free survival (PFS) [Time frame: 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) [Time frame: Every 3 months until consent withdraw, death, withdrawal study, or loss of follow-up, up to 100 weeks]

Eligibility criteria

Inclusion criteria

• Male or female, age≥ 18 years；
• 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;
• Tumor Her2 negative (IHC 0/1＋ or IHC 2＋ and FISH-).
• At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors （RECIST) 1.1;
• WBC≥3.0×10\^9 /L; ANC≥1.5×10\^9 /L; HB≥90 g/L; PLT≥75×10\^9 /L;
• 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)
• LVEF≥50%; male QTc≤450 mms, female QTc≤470 mms;
• ECOG 0\~1；
• Expected survival ≥ 3 months;
• Consent to contraception；
• Understand and voluntarily sign a written ICF and be willing to comply with all trial requirements.

Exclusion criteria

• History of other malignancies (except cured basal cell skin cancer, cervical carcinoma in situ etc.) within 5 years before study drug administration;
• Patients with central nervous system metastases with clinical symptoms;
• 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;
• Previous treatment with other adenovirus drugs within 28 days before the first dose of BioTTT001;
• Patients who have undergone any major surgery (except needle biopsy, etc.) or severe trauma within 14 days before the first dose of BioTTT001;
• Patients who have not recovered from the adverse reactions of previous treatments (the treatment-related toxicity ≤ grade 2, except for alopecia );
• Patients with primary immunodeficiency;
• 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);
• Patients with active infection requiring systemic anti-infective therapy;
• HBsAg positive, and blood HBV DNA≥100 IU/mL; anti-HCV positive; HIV positive; active syphilis;
• Patients with active tuberculosis or drug-induced interstitial lung disease；
• Patients with active inflammatory bowel disease ；
• NYHA≥ grade 3；
• Known allergy to the investigational drug or its components;
• Patients with prior organ transplants;
• Pregnant or lactating women;
• Other reasons judged by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06283121 · BJCT-CMU1H-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗