This is a first-in-human, single-arm, open-label, dose escalation prospective phase I clinical study to evaluate the Safety, Tolerability and Efficacy of TMT101 Injection Alone in patients with Unresectable, Metastatic or Advanced pancreatic cancer or Non-small Cell Lung Cancer(NSCLC) after Standard Treatment Failure. The primary objective is to evaluate the safety and tolerability of TMT101 Injection as monotherapy in patients with advanced pancreatic cancer and NSCLC, and to determine the recommended therapeutic dose (RD) of TMT101 Injection as monotherapy
The dose escalation trial adopts the "3+3" design , and about 3\~6 patients with advanced pancreatic cancer or non-small cell lung cancer are enrolled in each dose level to evaluate the safety of TMT101 Injection alone. Three dose levels are planned to be explored: 0.1 mg, 0.2 mg, and 0.4 mg. Once a week, intramuscular Injection , a total of 9 times (the first tumor assessment is performed in the 6th week (±7 days), the investigator can decide the follow-up medication arrangement according to the tumor evaluation results). Dose-limiting toxicities (DLTs) will be assessed for each dose level, and the DLT observation period will be within 21 days from the first dose. The initial dose is 0.1 mg with a dose reduction for safety reasons, the level of dose reduction will be discussed jointly between the investigator and the sponsor. If the highest dose level of 0.4 mg is not confirmed as a possible recommended therapeutic dose (RD), it may be escalated a higher dose to determine the possible RD under the condition that investigator and the sponsor to decide together
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Three dose levels are planned to be explored: 0.1 mg, 0.2 mg, and 0.4 mg. The initial dose is 0.1 mg with a dose reduction for safety reasons, the level of dose reduction will be discussed jointly between the investigator and the sponsor. TMT101 will be injected intramuscularly, Once a week,a total of 9 times
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
RECRUITINGdose-limiting toxicities (DLTs)
Occurrence of dose-limiting toxicities (DLTs) within 21 days since the first dose
Time frame: within 21 days since the first dose
treatment-emergent adverse events (TEAEs)
occurrence of treatment-emergent adverse events (TEAEs) and grade according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Time frame: up to 2 years
treatment related adverse event (TRAE)
Occurrence and grade of treatment related adverse event (TRAE) according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Time frame: up to 2 years
immune-related Adverse Event(irAE)
Occurrence and grade of immune-related Adverse Event(irAE)according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Time frame: up to 2 years
Serious Adverse Event(SAE)
Occurrence and grade of Serious Adverse Event(SAE)according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Time frame: up to 2 years
Recommended Dose(RD)
During the dose escalation phase, the MTD and/or available safety, biomarker, and efficacy data will be evaluated thoroughly to determine the RD of TMT101 Injection alone . Three dose levels are planned to be explored: 0.1 mg, 0.2 mg, and 0.4 mg. Once the initial dose is 0.1 mg with a dose reduction for safety reasons, the level of dose reduction will be discussed jointly between the investigator and the sponsor. If the highest dose level of 0.4 mg is not confirmed as a possible recommended therapeutic dose (RD), it may be escalated to a higher dose to determine the possible RD under the condition that investigator and the sponsor to decide together.
Time frame: the whole escalation phase within 21 days since the first dose
Objective response rate (ORR)
the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and iRECIST
Time frame: up to 2 years
Disease control rate (DCR)
the percentage of patients with CR or PR or stable disease (SD) as BOR according to RECIST v1.1 and iRECIST divided by the number of patients in the efficacy analysis set
Time frame: up to 2 years
Progression-free survival (PFS)
the time of first trial treatment until the first objective tumor progression according to RECIST v1.1 and iRECIST or death from any cause, whichever occurs first
Time frame: up to 2 years
Overall survival (OS)
the time of first trial treatment until death from any cause
Time frame: up to 2 years
Peak time (Tmax) of cationic lipids
Time frame: up to 9 weeks
Peak concentration (Cmax) of cationic lipids
Time frame: up to 9 weeks
Area under the drug concentration -time curve (AUC) of cationic lipids
Time frame: up to 9 weeks
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