Advanced Malignant Solid Tumor
Conditions
Brief summary
This is a first-in-human, open-label, multicenter Phase I/II study of MHB088C combined with MHB039A in patients with advanced malignant solid tumors. The study was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MHB088C and MHB039A combination therapy.
Detailed description
This first-in-human clinical trial of MHB088C and MHB039A combination therapy comprises two parts: a dose escalation phase and indication expansion phase. The dose escalation phase is an open-label, multicenter study including dose escalation and PK expansion cohorts. The primary objectives are to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of MHB088C combined with MHB039A in patients with advanced solid tumors, and to determine the maximum tolerated dose (MTD). Additional patients may be enrolled in the PK expansion part at dose levels that have completed DLT (dose-limiting toxicity) evaluation. Based on the safety, PK, and preliminary efficacy data from the completed DLT-evaluated dose levels, the sponsor will initiate the indication expansion phase to further evaluate the safety and efficacy of MHB088C and MHB039A combination therapy in patients with specific types of advanced solid tumors.
Interventions
Intravenous administration
Intravenous administration
Sponsors
Minghui Pharmaceutical (Hangzhou) Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntarily agrees to participate in the study and signs the informed consent form. 2. Age ≥ 18 years, no restriction on gender. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 4. Estimated life expectancy ≥ 3 months. 5. For the dose escalation stage: Histologically or cytologically confirmed advanced solid tumors that are refractory to standard therapy, intolerant to standard therapy, or have no standard treatment options. 6. For the dose expansion stage: Histologically or cytologically confirmed locally advanced or metastatic advanced solid tumors, not suitable for radical surgery and/or radical concurrent/sequential radiotherapy and chemotherapy. 7. At least one measurable lesion per RECIST v1.1 criteria. 8. Adequate bone marrow reserve and organ function. 9. Eligible participants of childbearing potential (males and females) must agree to take highly reliable contraceptive measures with their partners during the study and within at least 12 weeks after the last dose.
Exclusion criteria
1. History of ≥2 primary malignancies within 5 years prior to informed consent. 2. Received chemotherapy within 3 weeks, radiotherapy within 4 weeks, or biologic, endocrine, or immunotherapy within 4 weeks before dosing. 3. Medication of other unmarketed investigational drugs or therapies within 4 weeks before dosing. 4. Brain metastases, leptomeningeal disease, brainstem metastases, or spinal cord compression. 5. Underwent major organ surgery (excluding biopsy) or significant trauma within 4 weeks before the first dose of investigational drug or requiring elective surgery during the study. 6. Previous or concurrent gastrointestinal perforation, surgical procedures and wound healing complications, as well as bleeding events. 7. Received intravenous thrombolysis treatment within 2 weeks, except for preventive anticoagulation and antiplatelet therapy. 8. Vaccinated within 4 weeks before dosing. 9. Treated with systemic corticosteroids within 14 days before dosing. 10. Severe lung disease affecting pulmonary function. 11. Active systemic infection requiring treatment within 7 days before dosing. 12. Uncontrolled third-space effusion. 13. Serious cardiovascular or cerebrovascular diseases. 14. Known hypersensitivity or delayed allergic reaction to the investigational product or its components. 15. Drug abuse or other medical/psychiatric condition that may interfere with study participation or results. 16. Known alcohol or drug dependence. 17. Pregnant or breastfeeding women, or individuals planning to conceive.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| (Dose-Escalation Stage): Dose-Limiting Toxicity (DLT) and Maximum tolerated dose (MTD) for MHB088C and MHB039A combination therapy | Up to day 21 from the first dose for Q3W administration, or up to day 28 from the first dose for Q2W administration. | To determine the MTD for further evaluation of IV administration of MHB088C and MHB039A combination therapy in subjects with advanced solid tumors. |
| (Dose-Expansion Stage): Objective tumor response (ORR) determined by investigators according to RECIST v1.1 | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years | Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). ORR is evaluated by the number of participants with best overall response of CR and PR (Confirmed CR/PR assessment require at least 1 repeat). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DOR) determined by investigators according to RECIST v1.1 | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years | DoR was defined as the period from the first occurrence of CR or PR to PD or death from any cause. If no PD or death after CR/PR, the cut-off date of progression-free survival (PFS) would be used \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\]. |
| Disease control rate (DCR) determined by investigators according to RECIST v1.1 | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years | Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). DCR was evaluated by the number of participants with best overall response of CR, PR and stable disease (SD) \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks); SD shall be assessed at least 5 weeks after the first dose\]. |
| Incidence and severity of adverse events (AEs) | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years. | AE assessed by investigator exclusively related to subject's underlying disease or medical condition \[graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0\]. |
| Overall survival (OS) | Baseline up until death up to approximately 5 years | OS was defined as the time from random assignment or first dose to death from any cause. |
| Progression-free survival (PFS) determined by investigators according to RECIST v1.1 | Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years | Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). PFS was defined as the time from random assignment (dose expansion stage) or first dose (dose escalation stage) to PD or death from any cause. |
| Pharmacokinetic (PK) parameters of total antibody, ADC, and free toxin at various time points | From pre-dose to 22 days after the first dose | The PK parameters at different time points include:Area Under the Concentration-Time Curve (AUC) |
Countries
China
Contacts
Primary ContactVP of R&D
Outcome results
None listed