An Open-label, Multicenter Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of JH021 Injection in Patients With Advanced Solid Tumors
An Open-label, Multicenter Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of JH021 Injection in Patients With Advanced Solid Tumors
This is an open-label, multicenter Phase I study designed to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary antitumor activity of JH021 injection in patients with advanced solid tumors. JH021 is a bispecific monoclonal antibody targeting EGFR and cMET. The study will assess JH021 in patients with advanced solid tumors for whom standard therapy is unavailable, intolerable, or no longer effective, and will provide data to support further clinical development.
Inclusion Criteria:
Male or female participants aged 18 to 75 years, inclusive.
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.
At least one measurable lesion according to RECIST version 1.1.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Estimated life expectancy of at least 12 weeks.
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 <= 1.5 × upper limit of normal (ULN) ALT and AST <= 3 × ULN
For participants with liver metastases:
Total bilirubin <= 2.5 × ULN ALT and AST <= 5 × ULN
Renal function:
Serum creatinine <= 1.5 × ULN or creatinine clearance >= 60 mL/min (calculated by Cockcroft-Gault formula)
Coagulation function:
INR <= 1.5 × ULN PT <= 1.5 × ULN APTT <= 1.5 × ULN Fibrinogen >= 0.75 × lower limit of normal
Women of childbearing potential and their partners must be willing to use effective contraception.
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.
Participants must be able to understand and comply with study procedures, voluntarily participate in the study, and sign written informed consent.
Exclusion Criteria:
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).
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.
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.
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 in the absence of active autoimmune disease; short-term corticosteroids >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).
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.
Active infection requiring systemic treatment within 2 weeks before first dose, including active tuberculosis or pneumonia of any grade.
Known interstitial lung disease.
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.
Toxicities from prior antitumor therapy that have not recovered to <= Grade 1 according to NCI-CTCAE v6.0, except alopecia, Grade 2 hypoparathyroidism, laboratory abnormalities allowed by the inclusion criteria, or toxicities considered by the investigator to pose no safety risk.
Severe concomitant diseases, including active gastrointestinal bleeding, intestinal obstruction, paralytic ileus, glaucoma, uncontrolled diabetes mellitus, or other serious medical conditions.
Deep vein thrombosis.
Pleural effusion, pericardial effusion, or ascites that cannot be controlled with appropriate intervention within 4 weeks before first dose. Small effusions detectable only by imaging are allowed.
Major cardiovascular disease within 6 months before first dose, including severe arrhythmia, acute myocardial ischemia, unstable angina, congestive heart failure (New York Heart Association class >=2), left ventricular ejection fraction <50%, history of long QT syndrome or confirmed family history of long QT syndrome, or QTcF >450 msec in males or >470 msec in females.
Hypertension not controlled by standard treatment (systolic blood pressure >=140 mmHg and/or diastolic blood pressure >=90 mmHg).
Cerebrovascular accident within 6 months before first dose, including transient ischemic attack or stroke.
History of peripheral neuropathy of Grade 2 or higher.
Known history of alcohol abuse or drug abuse, except for those who have stopped drinking alcohol.
Prior organ transplantation.
Pregnant or breastfeeding women, women planning pregnancy, women of childbearing potential not using reliable contraception, sexually active men unwilling to use contraception during the study and for 3 months after the last dose, or men planning to donate sperm during this period.
Any medical, psychiatric, or other condition or circumstance that, in the investigator's opinion, may negatively affect participant safety or the reliability of study data.
Known allergy or hypersensitivity to any component of the JH021 formulation.
Prior treatment with EGFR monoclonal antibodies, c-MET monoclonal antibodies, c-MET antibody-drug conjugates, c-MET small-molecule TKIs, or EGFR/c-MET bispecific antibodies.
wangyanmin@biotechplc.com13911386413
Chongqing, Chongqing Municipality, China
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