advanced solid tumor
Conditions
Interventions
Phase ?a: Dose Escalation Study
:Explore dosage ranges of 150mg, 450mg, 900mg, 1400mg, 1800mg, totaling 5 dosage levels, JH021 injection
Phase ?b: Dose Expansion Study :Based on the RDE (Recommended Dose for Expansion) determined in Phase Ia, one or more dose groups will be established for JH021 Injection.
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Male or female participants aged 18 to 75 years, inclusive. 2. Histologically or cytologically confirmed malignancy with disease progression since the most recent antitumor therapy, and for whom standard treatment is unavailable, not tolerated, or refused. Part Ia: patients with advanced solid tumors. Part Ib: patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations (EGFR exon 19 deletion or exon 21 L858R) detected in tumor tissue or plasma ctDNA, who are resistant to third-generation EGFR-TKIs and have progressed after platinum-containing chemotherapy, or have no standard treatment available. 3. At least one measurable lesion according to RECIST version 1.1. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Estimated life expectancy of at least 12 weeks. 6. Adequate organ function, defined as follows: Bone marrow function: Absolute neutrophil count >= 1.5 × 10^9/L Platelet count >= 100 × 10^9/L Hemoglobin >= 90 g/L, without transfusion, erythropoietin, granulocyte colony-stimulating factor, hepatoprotective therapy, or other medical supportive treatment within 2 weeks before dosing Hepatic function: Total bilirubin = 60 mL/min (calculated by Cockcroft-Gault formula) Coagulation function: INR = 0.75 × lower limit of normal 7. Women of childbearing potential and their partners must be willing to use effective contraception. 8. Women of childbearing potential must have a negative serum human chorionic gonadotropin (HCG) test within 72 hours before first dose. Women are considered not of childbearing potential if they are postmenopausal for at least 12 months or have undergone hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or tubal ligation. 9. Participants must be able to understand and comply with study procedures, voluntarily participate in the study, and sign written informed consent.
Exclusion criteria
Exclusion criteria: 1. Known symptomatic or untreated central nervous system metastases, including leptomeningeal metastases. The following are allowed: lesions stable for at least 4 weeks after radiotherapy before first dose, as confirmed by MRI/CT; no uncontrolled neurological symptoms or signs, such as seizures, headache, central nausea/vomiting, progressive neurological dysfunction, or papilledema; asymptomatic untreated brain metastases not requiring local treatment (such as radiotherapy) or systemic treatment (such as mannitol or corticosteroids). 2. History of another malignancy within 5 years before first dose, except for malignancies treated curatively with no recurrence, including non-melanoma skin cancer, cervical carcinoma in situ, ductal carcinoma in situ or lobular carcinoma in situ of the breast, and localized prostate cancer. 3. Receipt of chemotherapy, targeted therapy, or other systemic antitumor therapy within 4 weeks or 5 half-lives before first dose, whichever is shorter; or receipt of Chinese herbal medicine or Chinese patent medicine for antitumor treatment within 2 weeks before first dose. 4. Continuous systemic treatment with corticosteroids at a dose >10 mg/day prednisone equivalent or other immunosuppressive therapy within 14 days before first dose or during the study. Exceptions: inhaled or topical corticosteroids at 10 mg/day prednisone equivalent for prophylaxis (e.g., contrast allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reaction after allergen exposure). 5. Major surgery or radical radiotherapy within 4 weeks before first dose; palliative radiotherapy within 2 weeks before first dose; or therapeutic radiopharmaceuticals (e.g., strontium, samarium) within 8 weeks before first dose. 6. Active infection requiring systemic treatment within 2 weeks before first dose, including active tuberculosis or pneumonia of any grade. 7. Known interstitial lung disease. 8. Known HIV antibody positivity; active hepatitis B virus infection (participants with positive HBsAg require HBV-DNA testing and are excluded if HBV-DNA is positive); active hepatitis C virus infection (positive HCV antibody and positive HCV-RNA); or positive syphilis antibody test. 9. Toxicities from prior antitumor therapy that have not recovered to =2), left ventricular ejection fraction 450 msec in males or >470 msec in females. 14. Hypertension not controlled by standard treatment (systolic blood pressure >=140 mm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicities (DLTs); Maximum tolerated dose (MTD) and/or recommanded dose for expansion (RP2D) of JHO21 in Part Ia;Objective response rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| To characterize the pharmacokinetic profile of JH021, including but not limited to Cmax, Tmax, AUC, t1/2, CL, and Vd, as applicable.;Incidence of anti-drug antibodies (ADAs) in Part Ia;Preliminary antitumor activity in Part Ia; Incidence of anti-drug antibodies (ADAs) in Part Ib; | — |
Countries
China
Contacts
Public ContactCaicun Zhou
Shanghai East Hospital
Outcome results
None listed