A Study of MHB088C Combined With MHB039A in Patients With Advanced Malignant Solid Tumors

Not Applicable

Recruiting

• Conditions: Advanced Malignant Solid Tumor
• Interventions: Drug: MHB088C for Injection; Drug: MHB039A for Injection

• Registration Number: NCT07126665
• Lead Sponsor: Minghui Pharmaceutical (Hangzhou) Ltd

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.

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-11
• Study First Submitted QC: 2025-08-11
• Study First Posted: 2025-08-17
• Study Start: 2025-09-18
• Last Update Submitted: 2025-11-16
• Last Update Posted: 2025-11-18
• Primary Completion: 2029-08
• Study Completion: 2031-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 116

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose escalation phase: cohort 1	MHB088C for Injection	Subjects will receive MHB088C Q2W in combination with MHB039A Q2W by intravenous administration.
Dose escalation phase: cohort 1	MHB039A for Injection	Subjects will receive MHB088C Q2W in combination with MHB039A Q2W by intravenous administration.
Dose escalation phase: cohort 2	MHB088C for Injection	Subjects will receive MHB088C Q2W in combination with MHB039A Q2W by intravenous administration.
Dose escalation phase: cohort 2	MHB039A for Injection	Subjects will receive MHB088C Q2W in combination with MHB039A Q2W by intravenous administration.
Indication expansion phase: cohort 3	MHB088C for Injection	Subjects will receive MHB088C Q2W in combination with MHB039A Q2W by intravenous administration.
Indication expansion phase: cohort 3	MHB039A for Injection	Subjects will receive MHB088C Q2W in combination with MHB039A Q2W by intravenous administration.
Indication expansion phase: cohort 4	MHB088C for Injection	Subjects will receive MHB088C Q2W in combination with MHB039A Q2W by intravenous administration.
Indication expansion phase: cohort 4	MHB039A for Injection	Subjects will receive MHB088C Q2W in combination with MHB039A Q2W by intravenous administration.

Primary Outcome Measures

Name	Time	Method
(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 Outcome Measures

Name	Time	Method
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 \[graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0\].
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:Maximum Plasma Concentration (Cmax)
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) \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks); SD shall be assessed at least 5 weeks after the first dose\].
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.
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.

Trial Locations

Locations (1)

Ethics Committee of Shanghai East Hospital; 🇨🇳 Shanghai, Shanghai Municipality, China