Advanced Cancer
Conditions
Brief summary
TQB2102 is an antibody-drug conjugate comprised of a humanised antibody against Human Epidermal Growth Factor Receptor 2 (HER2), a enzyme-cleavable linker, and a topoisomerase I inhibitor payload, which combine the ability of antibodies to specifically target tumour cells with the highly potent killing activity of drugs with payloads too toxic for systemic administration. This is a phase I study to evaluate the safety, tolerability and effectiveness of TQB102 injection in subjects with advanced malignancies.
Interventions
TQB2102 is an antibody-drug conjugate comprised of a humanised antibody against HER2, a enzyme-cleavable linker, and a topoisomerase I inhibitor payload.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study; * Male or female patient 18 to 75 years of age, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and life expectancy ≥12 weeks; * Histologically or cytologically confirmed, locally advanced tumors, Priority will be given to subjects with HER2 positive solid tumo; * Malignant tumor that failed from standard treatment or had no standard treatment; * According to the RECIST 1.1 standard, patient with at least one evaluable lesion; * The main organs function well; * Male or female patient had no plans to become pregnant and voluntarily took effective contraceptive measures from agree with the study to at least 6 months after the last dose of study drug.
Exclusion criteria
* Concurrent secondary malignancy or other malignancy with no evidence of disease for more than 3 years; * History of uncontrolled intercurrent illness; * Major surgical procedure, radiotherapy, chemotherapy, or immunotherapy within 4 weeks prior to first dose; * Patients with known symptomatic brain metastases; * Receiving any other investigational agent within 4 weeks before first dose; * Patients with severe hypersensitivity after the use of monoclonal antibodies * History of interstitial lung disease or pneumonia; * Unstable or serious concurrent medical conditions, as assessed by the Investigators, that would substantially increase the risk-benefit ratio of participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) | During the first treatment cycle (21 days). | DLT was defined as toxicities that meet pre-defined severity criteria (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) toxicity assessment criteria), and assessed as having a suspected relationship to study drug that occurred within the first cycle (21 days) of treatment. |
| Maximum tolerated dose (MTD) | During the first treatment cycle (21 days). | MTD was defined as the highest dose at which dose-limiting toxicity (DLT) occurred in less than 33% of patients. |
| The occurrence rate of all adverse events (AEs) | From date of the first dose until 28 days after last dose or new anti-tumor treatment, whichever came first. | The occurrence of adverse events defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) |
| Dose escalation: recommended phase 2 dose (RP2D) | Up to 2 years | The RP2D of DT-9081 is determined using pharmacokinetics, pharmacodynamics and safety data of the dose escalation part of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal half-life (T1/2) | Before infusion, 15 minutes after infusion on Cycle1 Day1, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1 and Cycle6 Day1; 4 hours, 7 hours, 7days and 14days after infusion on Cycle1 Day1; 4 hours and 7 hours after infusion on Cycle3 Day1. each cycle is 21 day | Terminal plasma half-life is the time required to divide the plasma concentration by two. |
| Objective Response Rate (ORR) | Baseline up to 2 years. | Defined as the percentage of Complete Response (CR) plus partial response (PR) assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria |
| Overall survival(OS) | Baseline to the date of death from any cause, up to 2 years. | Overall survival refers to the time from the first treatment to death from any cause. |
| Duration of Response (DOR) | Baseline to the date of documented disease progression, up to 2 years. | Defined as the time from first documented response to documented disease progression. |
| Progression-free survival (PFS) | Baseline to the date of documented disease progression, up to 2 years. | Defined as the time from first documented response to documented disease progression. |
| Disease control rate (DCR) | Baseline up to 2 years. | Defined as the proportion of subjects with CR, PR, or SD (Stable Disease). |
| Immunogenicity | Before infusion on Cycle1 Day1, Cycle2 Day1, Cycle 4 Day1, Cycle7 Day1, Cycle12 Day1 (each cycle is 21 days). 90 days after the end of the last infusion. | Incidence of anti-drug antibody (ADA) |
| Area under the curve (AUC) | Before infusion, 15 minutes after infusion on Cycle1 Day1, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1 and Cycle6 Day1; 4hours, 7 hours, 7days and 14days after infusion on Cycle1 Day1; 4 hours and 7 hours after infusion on Cycle3 Day1. each cycle is 21 days | The area under the curve (AUC) of serum or plasma concentration of ADC drug, total antibody, and small molecule toxin. |
| Peak concentration (Cmax) | Before infusion, 15 minutes after infusion on Cycle1 Day1, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1 and Cycle6 Day1; 4 hours, 7 hours, 7days and 14days after infusion on Cycle1 Day1; 4 hours and 7 hours after infusion on Cycle3 Day1. each cycle is 21 days | Maximum observed concentration (Cmax) of ADC drug, total antibody, and small molecule toxin. |
Countries
China
Outcome results
None listed