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TQB2450 in patients with advanced malignant tumors: results from a phase I dose-escalation and expansion study
Junli Xue1, Liqiong Xue1, Wenbo Tang1
1Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Background:
Immune checkpoint inhibitor therapy has demonstrated impressive clinical benefits in multiple tumor types. TQB2450, a novel monoclonal antibody targeting programmed cell death ligand 1, has shown safety and efficacy in preclinical studies.
Objectives:
This first-in-human study aimed to evaluate the safety/tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of TQB2450 in patients with advanced malignant tumors.
Design And Methods:
In this phase I study, eligible patients with advanced malignant tumors received intravenous TQB2450 once every 3 weeks. This study consisted of a 3 + 3 dose-escalation phase (1-30 mg/kg) and a specific dose-expansion phase (1200 mg). The primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety. The secondary endpoints were PK, immunogenicity, and investigator-assessed response rate.
Results:
Between April 2018 and February 2020, 40 patients were enrolled (22 in the dose-escalation phase and 18 in the dose-expansion phase). No DLT was reported and the MTD was not reached. Grade ⩾3 or worse treatment-related treatment-emergent adverse events (AEs) occurred in 11 (27.50%) patients, with the most frequent being aspartate aminotransferase increased (5.00%), leukopenia (5.00%), and anemia (5.00%). Treatment-related serious AEs were reported in six patients, the most common of which was decompensated liver function (5.00%). No treatment-related death was reported. The maximum serum concentration of TQB2450 increased in a dose-proportional manner. Treatment-induced anti-drug antibodies were detected in 31.58% (12/38) of patients. The investigator assessed the objective response rate as 5.00% and the disease control rate was 52.50%, including 2 partial responses and 19 stable diseases. The median progression-free survival was 2.69 (95% confidence interval, 2.07-6.14) months.
Conclusion:
TQB2450 has a manageable safety profile with favorable PK and immunogenicity and has shown early evidence of clinical activity in advanced malignant tumors.
Clinicaltrialsgov Identifier:
NCT03460457.
Insights
TQB2450, a novel antibody targeting programmed cell death ligand 1, shows a manageable safety profile in advanced cancers. Early clinical activity was observed, with a 52.50% disease control rate in a Phase I trial.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- Immune checkpoint inhibitors (ICIs) offer significant clinical benefits across various cancers.
- TQB2450 is a new monoclonal antibody designed to target programmed cell death ligand 1 (PD-L1).
- Preclinical studies indicated promising safety and efficacy for TQB2450.
Purpose of the Study:
- To assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity of TQB2450.
- To evaluate the preliminary antitumor activity of TQB2450 in patients with advanced malignant tumors.
- To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of TQB2450.
Main Methods:
- A Phase I, first-in-human study involving a 3+3 dose-escalation (1-30 mg/kg) and dose-expansion (1200 mg) phase.
- Eligible patients with advanced malignant tumors received intravenous TQB2450 every 3 weeks.
- Primary endpoints included safety, MTD, and DLT; secondary endpoints were PK, immunogenicity, and response rate.
Main Results:
- No DLT or MTD was reached in 40 enrolled patients.
- Treatment-related adverse events (AEs) of Grade ≥3 occurred in 27.50% of patients; most common were elevated AST, leukopenia, and anemia.
- The objective response rate was 5.00%, with a disease control rate of 52.50% and median progression-free survival of 2.69 months.
Conclusions:
- TQB2450 demonstrates a manageable safety profile.
- The drug exhibits favorable pharmacokinetic and immunogenicity characteristics.
- Early clinical activity in advanced malignant tumors suggests therapeutic potential for TQB2450.
