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

NCT03856541 | Completed Phase 1

• 1 other identifier: SHR-A1403-I-101
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Solid Tumor

Keywords

advanced solid tumor; C-Met antibody drug conjugate; Safety; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• The assessment of Treatment-related Adverse Events of SHR-A1403 in subjects with advanced solid tumors

  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

  up to 24 months

• DLT

  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.

  up to 24 months

• MTD

  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.

  up to 24 months

Secondary Outcomes (12)

• Time to peak (Tmax) of serum concentration

  Up to 24 months

• Maximum serum concentration (Cmax)

  Up to 24 months

• Half-life (T1/2)

  Up to 24 months

• Clearance/ bioavailability (CL/F)

  Up to 24 months

• Apparent volume of distribution/bioavailability (Vd/F)

  Up to 24 months

Study Arms (1)

SHR-A1403 Dose Escalation

EXPERIMENTAL

SHR-A1403 given intravenously (IV).

Drug: SHR-A1403

Interventions

SHR-A1403 DRUG

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

Also known as: HTI-1066

SHR-A1403 Dose Escalation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at both the Screening and baseline visits;
• Life expectancy ≥12 weeks
• Diagnosed (histologically or cytologically) with solid tumors and documented as advanced or metastatic disease for which there is no known effective anti-tumor treatment (refractory to or relapsed from standard therapies);
• Subjects must have measurable lesion(s) per RECIST v1.1 guideline at the Screening visit.
• Adequate laboratory parameters during the Screening Period as evidenced by:
• Absolute neutrophil count (ANC)≥1.5×109/L (1,500/mm3)；
• Platelets ≥100×109/L (100,000/mm3)；
• Hemoglobin (Hgb) ≥9.0 g/dL (90 g/L)；
• Albumin levels ≥2.8 g/dL；
• Total bilirubin ≤1.5×ULN (≤3×ULN for subjects with liver metastases)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
• ×ULN; for subjects with liver metastases, ALT and AST ≤5×ULN；
• Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min based on Cockcroft-Gault equation；
• Subjects must have a washout period ≥4 weeks since the last dose of cytotoxic chemotherapy，non-cytotoxic chemotherapy(including any previous TKI treatment), any investigational therapy, any prior immuno-oncology or monoclonal antibody products administered and ≥6 weeks since the last dose of chemotherapy of mitomycin C or nitrosoureas prior to the first dose of SHR-A1403;
• Pregnancy and Contraception:

You may not qualify if:

• Known history of Grade 3 or Grade 4 hypersensitivity to any components (antibody-drug conjugate \[ADC\], total antibody, unconjugated toxin) of the SHR-A1403 product, or sensitivity to humanized monoclonal antibody products);
• Any radiation or surgery within 4 weeks prior to the first dose of SHR-A1403, except for minor palliative intent(this is to be discussed with sponsor);
• Unresolved toxicities from previous anticancer therapy,defined as toxicities not yet resolved to NCI CTCAE (current version) grade ≤1 at baseline (other than alopecia and other tolerable AEs upon discussion with sponsor) . Subjects with chronic grade 2 toxicities may be eligible at the discretion of the investigator and discussion with sponsor;
• Central nervous system tumors or active central nervous system (CNS) metastasis by imaging diagnosis;
• Cardiac disease (New York Heart Association \[NYHA\] classes II-IV) including myocardial infarction,unstable angina, congestive heart failure, or cardiac arrhythmia requiring treatment within a minimum 6 months before enrollment;
• Active HBV and HCV infection (HBV virus copy number\>50 IU/mL, HCV virus RNA positive);
• History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV) or other acquired or congenital immune- deficient disease, or history of any organ transplantation;
• Any other medical(such as severe hypertension, diabetes, thyroid disease, etc.) or psychiatric or social condition deemed by the investigator to be likely serious hazards to a subject's rights, safety, welfare, or interfere with ability to sign informed consent, cooperate and participate in the study, interpret the results.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Shanghai Cancer Center, Fudan University

Shanghai, 200032, China

Location

MeSH Terms

Interventions

SHR-A1403

Study Officials

• Xichun Hu, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: February 27, 2019
• Study Start: February 13, 2019
• Primary Completion: December 30, 2019
• Study Completion: May 7, 2020
• Last Updated: October 28, 2022

Record last verified: 2019-01

Locations

CN (1)