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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
BioTTT001 is administered as a single Intratumoral injection. The dose groups to be infusion were 5×10\^9 VP, 5×10\^10 VP and 5×10\^11 VP based on the 3+3 dose escalation principle.
The First Affiliated Hospital of China Medical Univeristy
Shenyang, Liaoning, China
Incidence of adverse events
The incidence and severity of all types of adverse events evaluated based on NCI-CTCAE V5.0 assessment
Time frame: 28 days within BioTTT001 injection
MTD
Maximum tolerated dose (MTD)
Time frame: 28 days within BioTTT001 injection
Plasma Adenovirus (ADV) copies
Pharmacokinetic Study (PK): Copies of ADV in plasma at various sampling points.
Time frame: 28 days within BioTTT001 injection
ADV copies in various sites
Viral Shedding Analysis: Copies of ADV in swabs of injection sites, rectal swabs, throat swabs, and urine samples at various sampling points.
Time frame: 28 days within BioTTT001 injection
Serum interleukin-12 (IL-12) level
Expression levels of IL-12 at various sampling points in serum.
Time frame: 28 days within BioTTT001 injection
Serum neutralizing antibody level
Immunogenicity assessment through neutralizing antibody detection.
Time frame: 28 days within BioTTT001 injection
ORR
Objective response rate (ORR) as assessed by the investigators.
Time frame: From 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
DCR
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Disease control rate (DCR) as assessed by the investigators.
Time frame: From 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
PFS
Progression-free survival (PFS) as assessed by the investigators.
Time frame: From 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