A Study of SHR-A1403 in Patients With Advanced Solid Tumor
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03856541|
Recruitment Status : Recruiting
First Posted : February 27, 2019
Last Update Posted : February 28, 2019
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumor||Drug: SHR-A1403||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||February 13, 2019|
|Estimated Primary Completion Date :||July 2020|
|Estimated Study Completion Date :||November 2020|
Experimental: SHR-A1403 Dose Escalation
SHR-A1403 given intravenously (IV).
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
Other Name: HTI-1066
- The assessment of Treatment-related Adverse Events of SHR-A1403 in subjects with advanced solid tumors [ Time Frame: up to 24 months ]Assessment of the incidence and severity of treatment-related Advanse events will be collected and analysed in all subjects who received at least 1 dose of SHR-A1403 with the current version of the NCI CTCAE
- DLT [ Time Frame: up to 24 months ]A DLT is considered at AE related to study drug unless there is a clear, well-documented, alternative explanation for the toxicity. Severity of AEs are graded according to the current version of the NCI CTCAE for the study, the occurence of the following drug related AEs during the first cycle(1 to 21days from the first infusion) will be considered a DLT by the investigator and SMC.
- MTD [ Time Frame: up to 24 months ]MTD is the highest dose whose toxicity probability was lower or close to the preset target level of toxicity probability (30% in this study) during the DLT observation in the dose escalation of SHR-A1403.
- Time to peak (Tmax) of serum concentration [ Time Frame: Up to 24 months ]Pharmacokinetics profile of SHR-A1403:Time to peak (Tmax) of serum concentration
- Maximum serum concentration (Cmax) [ Time Frame: Up to 24 months ]Pharmacokinetics profile of SHR-A1403:Maximum serum concentration (Cmax)
- Half-life (T1/2) [ Time Frame: Up to 24 months ]Pharmacokinetics profile of SHR-A1403:Half-life (T1/2)
- Clearance/ bioavailability (CL/F) [ Time Frame: Up to 24 months ]Pharmacokinetics profile of SHR-A1403:Clearance/ bioavailability (CL/F)
- Apparent volume of distribution/bioavailability (Vd/F) [ Time Frame: Up to 24 months ]Pharmacokinetics profile of SHR-A1403:Apparent volume of distribution/bioavailability (Vd/F)
- Area under curve (AUC) [ Time Frame: Up to 24 months ]Pharmacokinetics profile of SHR-A1403:Area under curve (AUC)
- Accumulation index (Rac) [ Time Frame: up to 24 months ]Pharmacokinetics profile of SHR-A1403:Accumulation index (Rac)
- The assessment of anti-drug antibody [ Time Frame: up to 24 months ]The serum of patients who are administered with intravenous infusion every three weeks (q3w) for a treatment cycle are collected at difinitive time points， Anti-SHR-A1403 antibody will be detected and measured.
- Preliminary efficacy assessments of SHR-A1403 [ Time Frame: up to 24 months ]Subjects will be assessed every other cycle using RECIST v1.1.
- C-Met expression levels in blood [ Time Frame: up to 24 months ]The exploratory biomarker, C-Met,from blood samples obtained pre- and post-treatment will be measured.
- C-Met expression levels in tumor tissue [ Time Frame: up to 24 months ]The exploratory biomarker, C-Met, from tumor tissue samples obtained pre- and post-treatment will be measured.
- The recommended Phase 2 dose (RP2D) of SHR-A1403 in subjects with advanced solid tumors [ Time Frame: up to 24 months ]When the dose escalation is accomplished, RP2D will be reported by the assessment of safety with CTCAE v4.03.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03856541
|Contact: Xichun Hu, MDemail@example.com|
|Contact: Chunlei Jin, MD,PhDfirstname.lastname@example.org|
|Shanghai Cancer Center, Fudan University||Recruiting|
|Shanghai, China, 200032|
|Contact: Xichun Hu, MD 0086-021-64175590 email@example.com|
|Principal Investigator:||Xichun Hu, MD||Fudan University|