A Study of MHB046C Injection in Patients With Advanced Solid Tumors

Official title

A Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of MHB046C Injection in Patients With Advanced Solid Tumors

Overview

This is a first-in-human, open-label, multicenter Phase I/II study of MHB046C in patients with advanced solid tumors. The study was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MHB046C monotherapy.

Detailed description

This first-in-human clinical trial of MHB046C comprises two parts: a dose escalation phase and an 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 MHB046C in patients with advanced solid tumors, and to determine the maximum tolerated dose (MTD). In this phase, 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. This phase is an open-label, multicenter, multi-cohort study designed to further evaluate the safety and efficacy of MHB046C monotherapy in patients with specific types of advanced solid tumors.

Interventions

• Drug MHB046C
  IV administration of MHB046C Q3W; Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression.

Primary outcome measures

• I (Dose-Escalation Stage): Maximum tolerated dose (MTD) for MHB046C [Time frame: Up to day 21 from the first dose]
• II (Dose-Expansion Stage): ORR determined by investigators according to RECIST v1.1 [Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years]

Secondary outcome measures (9)

• Incidence and severity of adverse events (AEs) [Time frame: Baseline up to 5 years]
• Pharmacokinetic (PK) parameters of total antibody, ADC, and free toxin at various time points [Time frame: From pre-dose to 22 days after the first dose]
• Pharmacokinetic (PK) parameters of total antibody, ADC, and free toxin at various time points [Time frame: From pre-dose to 22 days after the first dose]
• Immunogenicity [Time frame: From pre-dose to 30 days post end of treatment.]
• ORR determined by investigators according to RECIST v1.1 [Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years]
• Duration of response (DOR) determined by investigators according to RECIST v1.1 [Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years]
• Disease control rate (DCR) determined by investigators according to RECIST v1.1 [Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years]
• Progression-free survival (PFS) determined by investigators according to RECIST v1.1 [Time frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years]
• Overall survival (OS) [Time frame: Baseline up until death up to approximately 5 years]

Eligibility criteria

Inclusion criteria

• Voluntarily agrees to participate in the study and signs the informed consent form.
• Age ≥ 18 years, no restriction on gender.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Estimated life expectancy ≥ 3 months.
• Able to understand and comply with the study protocol and follow-up procedures.
• Histologically or cytologically confirmed advanced solid tumors that are refractory to standard therapy, intolerant to standard therapy, or have no standard treatment options.
• At least one measurable lesion per RECIST v1.1 criteria.
• Adequate organ function.

Exclusion criteria

• History of ≥2 primary malignancies within 5 years prior to informed consent.
• Received chemotherapy within 3 weeks, radiotherapy within 4 weeks (2 weeks for palliative bone radiotherapy), or biologic, endocrine, or immunotherapy within 4 weeks before first study dose.
• Brain metastases (unless asymptomatic, no edema, stable ≥4 weeks without steroids), leptomeningeal disease, brainstem metastases, or spinal cord compression.
• Severe lung disease affecting pulmonary function.
• Active systemic infection requiring treatment within 7 days before dosing.
• Serious cardiovascular or cerebrovascular diseases
• Uncontrolled third-space effusions not suitable for enrollment:
• Uncontrolled diabetes, including ketoacidosis or hyperosmolar state within 6 months.
• Significant bleeding, bleeding tendency, or non-healing wounds within 1 month before first dose.
• Known hypersensitivity or delayed allergic reaction to the investigational product or its components.
• Drug abuse or other medical/psychiatric condition that may interfere with study participation or results.
• Known alcohol or drug dependence.
• Pregnant or breastfeeding women, or individuals planning to conceive.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Guangdong Provincial People's Hospital — Guangzhou

Identifiers

NCT: NCT06985355 · MHB046C-A-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗