Advanced Solid Tumors
Conditions
Interventions
Dose Escalation:Intravenous JR8603
Dose Expansion:Intravenous JR8603
Sponsors
Harbin Medical University Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age>=18 years. 2. Histologically confirmed patients with locally advanced or metastatic solid tumors who have progressed during standard therapy or are intolerant to standard therapy or for which standard therapy is not available or have documented proof of refusal of standard therapy. 3. Confirmed presence of measurable lesions according to RECIST v1.1 criteria. 4. Life expectancy > = 3 months. 5. Good organ and bone marrow function, defined as: a. ANC>=1.5 × 10^9/L(>=l,500/mm3); b. Platelet count >=100× 10^9/L (=100,000/mm^3) (no platelet transfusion within 14 days prior to enrollment); c. TBIL =60 mL/min; f. INR, PT, and aPTT <=1.5 × ULN. If the patient is receiving anticoagulation, PT and aPTT must be within the intended range of anticoagulant therapy. 6. Patients with previously treated and stable central nervous system (CNS) metastases (including leptomeningeal carcinomatosis) are allowed to enroll, as determined by clinical examination and brain imaging, with no evidence of progression for at least 4 weeks after CNS-directed therapy. 7. Any clinically significant toxicity from prior therapy has recovered to Grade =1 according to NCI CTCAE v5.0 (with the exception of alopecia and grade 2 peripheral neuropathy). 8. ECOG performance status score of 0 or 1. 9. Male and female patients of childbearing potential willing to practice a traditional effective method of birth control with a failure rate of <1% during study treatment and for at least 6 months (females) and at least 3 months (males) after the last dose of study treatment (must include a barrier method of contraception, such as a condom or diaphragm containing spermicidal gel). Women of childbearing potential are defined as women who have had menarche and have not yet been postmenopausal (and amenorrhea or surgical sterilization without induction therapy for 2 years). For male patients whose partners are non-pregnant females of childbearing potential and female patients of childbearing potential, it is recommended to adhere to the correct use of 1 highly effective birth control method with an annual failure rate of less than 1%. Note: Sexual abstinence should only be considered a highly effective method of contraception if sexual intercourse with the opposite sex is avoided throughout the risk period associated with the trial drug. The reliability of abstinence should be assessed in the context of study duration, patient preference, and lifestyle of daily living. Unacceptable methods of birth control in this study include: a. periodic abstinence (calendar, symptomatic temperature, or post-ovulation); b. Extracorporeal ejaculation (interruption of sexual intercourse); c. Use spermicide only: d. Lactation amenorrhea. Egg and sperm donation or preservation is prohibited during enrollment in this study and for 90 days after the last dose of trial drug. 10. Negative blood pregnancy test result at screening and negative pregnancy test result (serum or urine) within 72 hours before the first dose of the test drug (only for female patients of childbearing potential). If the urine pregnancy test is positive or cannot be determined to be negative, a blood pregnancy test is required, which must be negative to determine the patient's elig
Exclusion criteria
Exclusion criteria: 1. Any condition that in the opinion of the Investigator would place the patient at an unacceptable risk or cause the patient to be unlikely to fully participate or comply with study procedures. 2. Received systemic anticancer chemotherapy, targeted agents, antibody therapy for cancer, immunotherapy for cancer, hormonal therapy, or an investigational agent within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study drug treatment. 3. Major surgery within 3 weeks prior to start of study drug treatment. 4. Radiation therapy within 4 weeks prior to start of study drug treatment (palliative radiation or stereotactic radiosurgery within 7 days prior to start of study drug treatment). Patients must have recovered from all acute radiotherapy-related toxicities. 5. Severe or unstable cardiac conditions including, but not limited to, congestive heart failure (New York Heart Association Class III or IV), ischemic heart disease, uncontrolled hypertension, uncontrolled cardiac arrhythmia requiring medication (Grade >= 2, according to NCI CTCAE v5.0), myocardial infarction within 6 months prior to starting study drug treatment, congenital long QT syndrome or QT interval corrected for heart rate using Fridericia's formula (QTcF) >470 msec at screening, and any other significant or unstable concurrent cardiac illness. 6. Severe or unstable medical condition including uncontrolled diabetes or unstable psychiatric condition. 7. Has a history of another active malignancy (a second cancer) within the previous 2 years except for localized cancers that are not related to the current cancer being treated, are considered cured, and, in the opinion of the Investigator, present a low risk of recurrence. These exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. 8. Active infection requiring systemic therapy (including asymptomatic infections with positive virus titers and the Investigator's judgment that worsening of the condition is likely with study drug or the condition will impair or prohibit a patient's participation in the study). 9. Known human immunodeficiency virus, hepatitis B virus (HBV) (i.e., hepatitis B surface antigen positive), or hepatitis C virus (HCV) (i.e., detectable HCV RNA). Note: Patients with a prior history of treated HBV infection who are antigen negative, patients with a prior history of treated HCV infection who are HCV RNA undetectable or patients with HIV who are on stable anti-retroviral therapy and have an undetectable viral load may be enrolled. 10. Pregnant (or intending to become pregnant) or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of DLTs;Adverse event;Vital sign;Physical examination;Electrocardiogram;Clinical laboratory measurements; | — |
Secondary
| Measure | Time frame |
|---|---|
| Plasma concentration;Overall response rate;Time to response;Duration of response;Disease control rate;Progression-free survival;Overall survival; | — |
Countries
China
Contacts
Public ContactZhang Yanqiao
Harbin Medical University Cancer Hospital
Outcome results
None listed