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

• Status: Unknown status
• Trial end date: 2020-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Criteria

Inclusion Criteria:

• 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)

• 2.5×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:

• Female subjects agree not to be pregnant or lactating from beginning of the study screening until 6 months after receiving the last treatment;

• Male and female subjects and their sexual partners are willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy from beginning of the study screening until 6 months after receiving the last treatment of study drug;

• A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year, when used consistently and correctly);

• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment and not be breast feeding. Female subjects of non-childbearing potential must be surgically sterile (i.e., bilateral tubal ligation or removal of both ovaries and/or uterus at least 6 months prior to dosing) OR naturally postmenopausal (spontaneous cessation of menses) for at least 24 consecutive months prior to dosing, with a follicle stimulating hormone (FSH) level at Screening of ≥40 mIU/mL;

• Willing and able to comply with clinic visits and study-related procedures;

• voluntarily participating in this clinical trial, understanding the study procedures and providing signed informed consent.

Exclusion Criteria:

• 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.