NCT03856541

A Study of SHR-A1403 in Patients With Advanced Solid Tumor

A Phase I, Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR-A1403 With Intravenous Infusion in Patients With Advanced Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Jiangsu HengRui Medicine Co., Ltd. · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

SHR-A1403 is a humanized IgG2, anti-C-Met monoclonal antibody conjugated to microtubule inhibitor (c-Met ADC).The aim of this study is to assess the safety and tolerability of SHR-A1403，to define the dose limited toxicity（DLT）and the maximum tolerated dose (MTD)，to evaluate the pharmacokinetics of SHR-A1403，to assess the antitumor activity of SHR-A1403 in patients with advanced solid tumors preliminarily and to recommend the reasonable dosage regimen of SHR-A1403 for the follow-up clinical trial.

Detailed description

This study is a phase I clinical trial of single arm，open-label，dose escalation with single and multiple doses.The safety,PK and preliminary efficacy of SHR-A1403 were evaluated respectively in the patients with advanced solid tumors that have invalid standard treatment or no standard and effective treatment.SHR-A1403 is administered with intravenous infusion every three weeks (q3w) for a treatment cycle.Dose limiting toxicities (DLT) observation will end after 3 weeks from the start of study treatment(21 days). The dose escalation is designed by Modified Toxicity Probability Interval-2 Designs（mTPI-2) and will continue until an MTD or preliminary RP2D is identified. 3 patients are enrolled and observed in the initial dose. After completing the DLT assessment, the next decision of dose escalation will be performed according to the mTPI-2 detailed dose climbing/descending plan. After each decision, 3 other patients will be enrolled in the next phase of dose escalation until the maximum number of subjects specified in the study protocol or the dose escalation terminated by the Safety Monitoring Committee(SMC). The study consists of 3 periods: Screening Period (up to 14 days before the first dose), Treatment Period, and Follow-up Period (up to 3 months after the last dose of study treatment). The safety and tolerability of SHR-A1403 will be assessed by ongoing reviews of clinical laboratory tests, Eastern Cooperative Oncology Group (ECOG) performance status, physical examinations, vital signs, ECG, and adverse events (AEs) as defined by the current version of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.03). Safety will be monitored throughout the study. Response assessment will be performed by the end of Cycle 2 (6 weeks after the first infusion). Subsequently, post-dose tumor response evaluations will be performed every 6 weeks for the first 6 months, then by every 12 weeks thereafter, and at short-term follow up. For subjects who discontinue study treatment, tumor imaging should also be performed at end of therapy. Tumor imaging will be performed for all subjects as feasible (e.g., may not be able to be performed in subjects who withdraw consent or would not be performed in subjects who are lost to follow-up) until documented progression of disease, intolerable toxicity, initiation of a new antitumor therapy, withdrawal of consent, or the occurrence of death or end of study, whichever occurs first. Blood samples collected pre-dose and post-dose will be analyzed for PK variables. In general, PK data analysis will include, but will not be limited to, time to maximal serum concentration (tmax), maximal serum concentration (Cmax), area under the curve from time 0 to Day 21 of Cycle 1 (AUC0-21d), and observed terminal half life (t1/2) in Cycle 1; as well as concentration (average) (Cavg), area under the curve from time 0 to the end of the dosing interval (Day 21) after repeated dosing (AUC0-τ), t1/2, clearance at steady state (CLss), volume of distribution during terminal phase (Vz), and accumulation ratio (Rac) (AUC0-τ/AUC0-21d) for longer-term analyses. Tumor tissue samples will be collected in pre- and post-treatment for additional exploratory biomarkers. Tumor samples of Pre-treatment (i.e., Screening) could be obtained for c-Met status analysis by IHC through either subject's archived paraffin tissues or fresh (preferred) biopsies, and tumor tissue biopsies of post-treatment at C2D8 , pre- and post-treatments are optional. In addition, blood samples will also be collected in pre- and post-treatment and serum will be prepared for circulatory biomarker (soluble c-Met) analysis by ELISA at screening and C2D8; these blood samples are required in the study.

Conditions

• Advanced Solid Tumor

Interventions

Type	Name	Description
DRUG	SHR-A1403	SHR-A1403 is a humanized anti C-Met immunoglobulin G2 (IgG2) monoclonal antibody conjugated with microtubule inhibitor. SHR-A1403 is provided as the lyophilized powder,40 mg/vial.SHR-A1403 was given intravenously per 3 weeks at the day 1.Intravenous infusion over 30 min

Timeline

• Start date: 2019-02-13
• Primary completion: 2019-12-30
• Completion: 2020-05-07
• First posted: 2019-02-27
• Last updated: 2022-10-28

Locations

1 site across 1 country: China