Phase 1/2, Two-Part, Multi-center, Open-label, Dose Escalation and Dose Expansion First-In-Human Study to Evaluate the Safety/Tolerability, Pharmacokinetics and Efficacy of MHB088C in Participants With Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Enrollment
- 48
- Locations
- 3
- Primary Endpoint
- Evaluate the incidence of dose-limiting toxicities (DLTs)
Overview
Brief Summary
This study will evaluate the safety/tolerability, pharmacokinetics and efficacy of MHB088C in participants with advanced or metastatic solid tumors.
Detailed Description
This study is the first-in-human (FIH) trial of MHB088C, which contains two parts: dose escalation (part one) and dose expansion (part two).
Part one: Dose Escalation Study of MHB088C Monotherapy in Participants with Advanced or Metastatic Malignant Solid Tumors The dose escalation part is an open-label, multi-center study in which the eligible participants with advanced or metastatic solid tumors will be enrolled to receive MHB088C monotherapy to assess the safety and tolerability of MHB088C in participants with advanced or metastatic solid tumors, to determine the maximum tolerated dose (MTD) of MHB088C, and to assess its pharmacokinetic profile and preliminary efficacy.
The dose expansion part is an open-label, multi-center, multi-cohort expansion study in which participants with advanced or metastatic solid tumors of some predefined cancer types will be enrolled to receive MHB088C monotherapy. Participants with same types of solid tumors will be randomised into different selected dose groups and will be treated with the corresponding dose. This study is designed to assess the preliminary efficacy and safety of MHB088C monotherapy in participants with some types of advanced or metastatic solid tumors, so as to determine the recommended phase 2 dose (RP2D); and to assess the immunogenicity and pharmacokinetic profiles of MHB088C.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants enrolled must meet all of the following criteria:
- •General conditions
- •Participants voluntarily agree to participate in the study and sign the Informed Consent Form.
- •Aged ≥18years, without gender limitation.
- •Has an Eastern Cooperative Oncology Group Performance score (ECOG) 0 \~
- •Has a life expectancy of ≥ 3 months.
- •Eligible participants of childbearing potential (males and females) must agree to take highly reliable contraceptive measures (hormone or barrier method, or absolute abstinence, etc.) with their partners during the study and within at least 90 days after the last dose and agree not to retrieve, freeze or donate sperm or ova from screening to at least 3 months after the last dose of investigational drug; female participants of childbearing potential must have a negative results of blood pregnancy test within 7 days before the first dose of investigational drug, and must be non-lactating.
- •Understand study requirements, willing and able to comply with study and follow-up procedures.
- •Neoplasm-related criteria
- •Part one: Histologically or cytologically confirmed unresectable advanced or metastatic malignant solid tumors, that is progressed or intolerant with standard of care (SOC), or for which no SOC regimens are available;
Exclusion Criteria
- •Participants will be not enrolled if they meet any of the following exclusion criteria:
- •Neoplasm-related criteria:
- •Has more than 2 primary malignancies (except curatively treated non-melanoma skin cancer, in situ disease, and other curatively malignancies have considered cured) within 5 years before signing of Informed Consent Form.
- •Has received chemotherapy within 3 weeks, or have received anti-tumor treatment including radiation therapy, biologic therapy, endocrine therapy, immunotherapy, etc. within 4 weeks before the first dose of investigational product; or participants with the following conditions:
- •Medication of nitrosourea or mitomycin C within 6 weeks before the first dose of investigational drug; Medication of oral fluoropyrimidines and small molecule targeted agents within 5 half-lives before the first dose of investigational drug; Medication of traditional Chinese medicine with anti-tumor indication within 2 weeks before the first dose of investigational drug.
- •Medication of other unmarketed investigational drugs or therapies within 4 weeks before the first dose of investigational drug.
- •Presence of brain metastases and/or leptomeningeal carcinomatosis. Participants previously treated for brain metastases may be considered to be enrolled in this study, provided they have been in stable condition for at least 1 month, have no progression confirmed by radiographic examination within 4 weeks before the first dose of study treatment, all neurological symptoms have stabled, there is no evidence of new or enlarging brain metastases, and radiation or surgical therapy is discontinued for at least 28 days before the first dose of study treatment and steroid therapy at the dose of ≤10 mg/day or similar drugs at equivalent dose within 14 days before the first dose and during the study. This exception does not include carcinomatous meningitis, which should be excluded regardless of clinical stability.
- •Has previously received same target therapy.
- •Has adverse reactions from previous anti-tumor treatment that have not recovered to ≤ CTCAE 5.0 Grade 1 (except for toxicities without safety risks as determined by the investigator, such as alopecia, hypothyroidism stably managed by hormone replacement therapy, etc.).
- •General conditions:
Arms & Interventions
MHB088C administered
MHB088C will be administered intravenously at a frequency of once every 2 weeks (Q2W).
Intervention: MHB088C for Injection (Drug)
Outcomes
Primary Outcomes
Evaluate the incidence of dose-limiting toxicities (DLTs)
Time Frame: through study completion, an average of 1 year
Dose-limiting toxicities are defined as side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment
Evaluate the incidence of adverse events (AEs)
Time Frame: through study completion, an average of 1 year
Adverse events was assessed by investigator(s) according to NCI-CTCAE v5.0
Determine the recommended Phase 2 dose (RP2D) of MHB088C
Time Frame: through study completion, an average of 1 year
The recommended phase 2 dose (RP2D) is determined traditionally by dose-limiting toxicities.
Secondary Outcomes
- Pharmacokinetics (PK) parameter: Maximum concentration (Cmax)(Within 5 cycles (each cycle is 28 days))
- PK parameter: Systemic clearance (CL)(Within 5 cycles (each cycle is 28 days))
- PK parameter: Terminal or apparent terminal half-life (t1/2)(Within 5 cycles (each cycle is 28 days))
- Duration of Response (DOR)(through study completion, an average of 1 year)
- Progression Free Survival (PFS)(through study completion, an average of 1 year)
- Immunogenicity Assessment(Within 5 cycles (each cycle is 28 days))
- PK parameter: Time to maximum concentration (Tmax)(Within 5 cycles (each cycle is 28 days))
- PK parameter: Trough concentration (Ctrough)(Within 5 cycles (each cycle is 28 days))
- Objective Response Rate (ORR)(through study completion, an average of 1 year)
- PK parameter: Area under the concentration-time curve (AUC)(Within 5 cycles (each cycle is 28 days))
- Disease Control Rate (DCR)(through study completion, an average of 1 year)