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A Clinical Study Evaluating the Safety and Efficacy of BioTTT001 in Patients with Malignant Solid Tumors

Phase 1
Conditions
Solid Tumor
Interventions
Registration Number
NCT06215846
Lead Sponsor
Beijing Bio-Targeting Therapeutics Technology Co., Ltd
Brief Summary

This is a Phase 1 open-label study to evaluate the safety, tolerability, and pharmacokinetics of Recombinant Human nsIL12 Oncolytic Adenovirus Injection (BioTTT001) at dose of 5×10∧9VP、5×10∧10VP、5×10∧11VP in Patients With Malignant Solid Tumors. Subjects will be treated with a single dose of BioTTT001 Injection after the screening period.

Detailed Description

This study is a single arm, open label, single center dose escalation trial. Three study drug dosage groups are pre-set, namely 5 × 10∧9VP、5 × 10∧10VP、 5 × 10∧11VP. According to the principle of dose escalation from low to high, the "3+3" dose escalation method is adopted. In theory, in order to protect the safety of the subjects, during the DLT observation phase of the same dose group, the first subject in each dose group can only be enrolled in the second subject after at least 2 weeks after administration. The DLT observation period for each subject is 28 days after the first administration, and the last subject in each dose group can only enter the next dose escalation after completing the DLT observation period. At least 3 subjects are enrolled in each dose group, and each subject only receives one corresponding dose.

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
12
Inclusion Criteria
  1. Age range from 18 to 80 years old (including the threshold), no gender restrictions.
  2. Patients with histologically and/or cytologically confirmed malignant solid tumors, who have experienced at least one-line standard treatment failure or intolerance, or lack standard treatment options. Focus on malignancies in the head and neck, colorectal cancer, skin malignancies, and cervical cancer.
  3. At least one assessable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  4. Assessed by the investigators to have lesions suitable for intratumoral injection (assessable lesions and intratumoral injection lesions can refer to the same lesion).
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. 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 ).

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BioTTT001 injectionBioTTT001 injectionBioTTT001 is administered as a single Intratumoral injection. The dose groups to be infusion were 5×10\^9 viral particle (VP) ,5×10\^10 VP and 5×10\^11 VP based on the 3+3 dose escalation principle.
Primary Outcome Measures
NameTimeMethod
Incidence of adverse events28 days within BioTTT001 injection

The incidence and severity of all types of adverse events evaluated based on NCI-CTCAE V5.0 assessment

MTD28 days within BioTTT001 injection

Maximum tolerated dose (MTD)

Secondary Outcome Measures
NameTimeMethod
Serum neutralizing antibody level28 days within BioTTT001 injection

Immunogenicity assessment through neutralizing antibody detection.

Plasma Adenovirus (ADV) copies28 days within BioTTT001 injection

Pharmacokinetic Study (PK): Copies of ADV in plasma at various sampling points.

ORRFrom date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Objective response rate (ORR) as assessed by the investigators.

DCRFrom date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Disease control rate (DCR) as assessed by the investigators.

PFSFrom date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Progression-free survival (PFS) as assessed by the investigators.

ADV copies in various sites28 days within BioTTT001 injection

Viral Shedding Analysis: Copies of ADV in swabs of injection sites, rectal swabs, throat swabs, and urine samples at various sampling points.

Serum interleukin-12 (IL-12) level28 days within BioTTT001 injection

Expression levels of IL-12 at various sampling points in serum.

Trial Locations

Locations (1)

The First Affiliated Hospital of China Medical Univeristy

🇨🇳

Shenyang, Liaoning, China

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