Advanced Solid Tumor
Conditions
Brief summary
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.
Interventions
BIOLOGICALJH021
JH021 is an EGFR/cMET bispecific monoclonal antibody administered by intravenous infusion.
Sponsors
Biotech Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-group assignment. All enrolled participants will receive JH021 injection in an open-label, multicenter phase I study with dose-escalation and dose expansion parts.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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 \<= 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 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
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 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). 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 \<= 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. 10. Severe concomitant diseases, including active gastrointestinal bleeding, intestinal obstruction, paralytic ileus, glaucoma, uncontrolled diabetes mellitus, or other serious medical conditions. 11. Deep vein thrombosis. 12. 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. 13. 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. 14. Hypertension not controlled by standard treatment (systolic blood pressure \>=140 mmHg and/or diastolic blood pressure \>=90 mmHg). 15. Cerebrovascular accident within 6 months before first dose, including transient ischemic attack or stroke. 16. History of peripheral neuropathy of Grade 2 or higher. 17. Known history of alcohol abuse or drug abuse, except for those who have stopped drinking alcohol. 18. Prior organ transplantation. 19. 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. 20. 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. 21. Known allergy or hypersensitivity to any component of the JH021 formulation. 22. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicities (DLTs) of JH021 in Part Ia | At the end of cycle 1(one cycle is 28 days) | To evaluate the safety and tolerability of JH021 and identify dose-limiting toxicities during the dose-escalation phase. |
| Maximum tolerated dose (MTD) and/or recommanded dose for expansion (RP2D) of JHO21 in Part Ia | Through completion of dose escalation, approximately up to 12 months | To determine the maximum tolerated dose (if reached) and identify the recommended dose for further clinical investigation. |
| Objective response rate (ORR) in Part Ib | From first dose until disease progression, assessed up to approximately 12 months | To evaluate the preliminary antitumor activity of JH021 monotherapy in patients with EGFR-mutant, locally advanced or metastatic NSCLC who are resistant to third-generation EGFR-TKIs and have progressed after platinum-containing chemotherapy, or have no standard treatment available, as assessed by investigators according to RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration (Cmax) | From first dose through the PK assessment period, approximately up to 12 months | To characterize the maximum observed plasma concentration of JH021 |
| Time to maximum plasma concentration (Tmax) of JH021 | from the first dose up to approximately 12 months | To characterize the time to maximum observed plasma concentration of JH021. |
| Area under the plasma concentration-time curve (AUC) of JH021 | From first dose up to approximately 12 months | To characterize the systemic exposure to JH021 based on the area under the plasma concentration-time curve |
| Terminal elimination half-time (t1/2) of JH021 | From first dose up to approximately 12 months | To characterize the terminal elimination half-time of JH021 |
| Incidence of anti-drug antibodies (ADAs) in Part Ia | From first dose through the immunogenicity assessment period, approximately up to 12 months | To evaluate the immunogenicity of JH021 by assessing the presence of anti-drug antibodies |
| Preliminary antitumor activity in Part Ia | From first dose until disease progression, assessed up to approximately 12 months | To evaluate the preliminary antitumor activity of JH021 in patients with advanced solid tumors, as assessed by investigators according to RECIST v1.1. |
| Incidence of adverse events(AE) | From the first dose up to approximately 12 months | to eveluate the safety of JH021 by assessing the incidence of advers events |
| Incidence of serious adverse events(SAE) | From the first dose up to approximately 12 months | to eveluate the safety of JH021 by assessing the incidence of serious advers events |
| Incidence of anti-drug antibodies (ADAs) in Part Ib | From first dose through the immunogenicity assessment period, approximately up to 12 months | To evaluate the immunogenicity of JH021 in Part Ib by assessing the presence of anti-drug antibodies. |
Countries
China
Contacts
CONTACTYanmin Wang, master
PRINCIPAL_INVESTIGATORCaicun Zhou, Doctor
Shanghai East Hospital
Outcome results
None listed