Advanced or Metastatic Solid Tumors
Conditions
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.
Interventions
MHB088C for Injection, an antibody drug-conjugated molecule (ADC)
Sponsors
Minghui Pharmaceutical Pty Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single group contains two study parts
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- Participants enrolled must meet all of the following criteria: General conditions 1. Participants voluntarily agree to participate in the study and sign the Informed Consent Form. 2. Aged ≥18years, without gender limitation. 3. Has an Eastern Cooperative Oncology Group Performance score (ECOG) 0 \ 1. 4. Has a life expectancy of ≥ 3 months. 5. 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. 6. Understand study requirements, willing and able to comply with study and follow-up procedures. Neoplasm-related criteria 7. 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; 8. Part two: Histologically or cytologically confirmed unresectable advanced or metastatic malignant solid tumors, that is relapsed or progressed following systemic treatment or no standard of care is available, including but not limited to the following types: non-small cell lung cancer (NSCLC); small cell lung cancer (SCLC); esophageal squamous cell carcinoma (ESCC); castration-resistant prostate cancer (CRPC); melanoma (MEL); colorectal cancer (CRC); pancreatic ductal adenocarcinoma (PDAC); head and neck squamous cell carcinoma (HNSCC); hepatocellular carcinoma (HCC); ovarian cancer (OC); endometrial cancer (EC); thyroid cancer (TC); and sarcoma (SARC). 1. Additional inclusion criteria for participants with NSCLC: Histologically or cytologically documented unresectable advanced or metastatic NSCLC and previous progressed during or after systematic treatment with platinum-contained doublet regimens chemotherapy and immune-checkpoint inhibitors (ICIs); refractory, intolerant or not suitable to the target therapy as per investigator discretion for participants with driver gene mutation. 2. Additional inclusion criteria for participants with SCLC: Histologically or cytologically documented unresectable advanced or metastatic SCLC and previous progressed during or after ≥1 lines of systematic treatment with platinum-based, doublet regimens chemotherapy and ICIs. 3. Additional inclusion criteria for participants with ESCC: Histologically or cytologically documented unresectable advanced or metastatic ESCC previous progressed during or after≥1 line platinum-based of systemic treatment. 4. Additional inclusion criteria for participants with CRPC: Histologically or cytologically documented CRPC without neuroendocrine differentiation or small cell elements; Underwent surgical or medical castration, with testosterone levels below 50 ng/dL; Objective progression as determined by radiographic after androgen deprivation therapy; Relapsed or progressed during or after at least one of the following medicines: abiraterone, enzalutamide, apalutamide, or darolutamide; Relapsed or progressed during or after≥ 1 line of docetaxel/mitoxantrone-based cytotoxic chemotherapy regimens for metastatic CRPC; With at least 1 documented lesion confirmed by either a bone scan or a CT/MRI scan. 5. Additional inclusion criteria for participants with MEL: Histologically or cytologically documented unresectable advanced or metastatic MEL and previous progressed during or after ≥1 line of systemic therapy including ICIs 6. Additional inclusion criteria for participants with CRC: Histologically or cytologically documented unresectable advanced or metastatic CRC and previous progressed during or after systematic chemotherapy containing oxaliplatin, irinotecan, fluorouracil and immunotherapy (for participants with MSI-H/dMMR). 7. Additional inclusion criteria for participants with PDAC: Histologically or cytologically documented unresectable advanced or metastatic PDAC and previous progressed during or after ≥ 1 line of systemic therapy in neoadjuvant, adjuvant, locally advanced or metastatic setting. 8. Additional inclusion criteria for participants with HNSCC: Histologically or cytologically documented unresectable advanced or metastatic HNSCC and previous progressed during or after ≥ 1 line of systemic therapy, including platinum-based chemotherapy and ICIs (combined or sequential therapy). 9. Additional inclusion criteria for participants with HCC: Histologically or cytologically documented unresectable advanced or metastatic HCC and previously progressed during or after ≥ 1 line of systemic therapy, including anti-vascular therapy and/or ICI therapy. 10. Additional inclusion criteria for participants with OC: Histologically or cytologically documented unresectable advanced or metastatic OC including less-common histology per National Comprehensive Cancer Network (NCCN) of epithelial ovarian cancer as well as fallopian tube cancer and primary peritoneal cancer and have relapsed or progressed during or after ≥ 1 line of platinum-based systemic chemotherapy treatment. 11. Additional inclusion criteria for participants with EC: Histologically or cytologically documented unresectable advanced or metastatic EC and recurrence after radical therapy, and previously treated and progressed during or after ≥ 1 line of standard systemic therapy. 12. Additional inclusion criteria for participants with TC: Histologically or cytologically documented unresectable advanced or metastatic TC and previous progressed during or after ≥ 1 line of systemic therapy including platinum-based chemotherapy or targeted therapy. 13. Additional inclusion criteria for participants with SARC: Histologically or cytologically documented unresectable advanced or metastatic SARC and previous progressed during or after ≥ 1 prior line of systemic therapy including doxorubicin-based chemotherapy. 9. Agree to provide the pre-existing diagnostic tumor samples for retrospective testing of target expression and other biomarkers (participants who agree but are unable to provide pre-existing tumor sample may also be enrolled). There is no minimum target expression level required for inclusion. 10. Has at least one measurable tumor lesion as per RECIST v1.1(generally, previously irradiated areas or locoregionally treated sites will not be considered as measurable lesions, unless these lesions have clearly progressed or still exist three months after radiotherapy); for participants with CRPC, evaluable lesions as defined by PCWG3 criteria or at least one measurable soft tissue tumor lesion as per RECIST v1.1 are required. Adequate bone marrow reserve and organ functions: 11. Adequate bone marrow reserve (without transfusion or colony-stimulating factor or equivalent within7 days before the screening period testing); Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelet count ≥ 100 × 10\^9/L; Hemoglobin ≥ 9.0 g/dL. 12. Adequate hepatic function (with reference to normal values specified by the clinical study site): Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); TBIL ≤ 2 × ULN if Gilbert's syndrome is present; TBIL ≤ 3.0 × ULN is permitted if direct bilirubin (DBIL) suggests extrahepatic obstruction. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) shall be ≤ 3 × ULN with non-hepatic tumors and without hepatic metastasis; AST and ALT shall be ≤ 5.0 × ULN with hepatic tumors or hepatic metastasis; 13. Adequate renal function (with reference to normal values specified by the clinical study site): Creatinine (Cr) ≤ 1.5 × ULN; when Cr \> 1.5 × ULN, only participants with creatinine clearance (Ccr) ≥ 50 mL/min can be enrolled (using Cockcroft-Gault formula); 14. Adequate coagulation function: Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, and international normalized ratio (INR) ≤ 1.5 × ULN. 15. Adequate cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram within 28 days before enrollment; New York Heart Association (NYHA) Class \< grade 3.
Exclusion criteria
\- Participants will be not enrolled if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the incidence of adverse events (AEs) | through study completion, an average of 1 year | Adverse events was assessed by investigator(s) according to NCI-CTCAE v5.0 |
| Evaluate the incidence of dose-limiting toxicities (DLTs) | 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 |
| Determine the recommended Phase 2 dose (RP2D) of MHB088C | through study completion, an average of 1 year | The recommended phase 2 dose (RP2D) is determined traditionally by dose-limiting toxicities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameter: Trough concentration (Ctrough) | Within 5 cycles (each cycle is 28 days) | MHB088C, total antibody, free toxin MH30010008 |
| PK parameter: Terminal or apparent terminal half-life (t1/2) | Within 5 cycles (each cycle is 28 days) | MHB088C, total antibody, free toxin MH30010008 |
| PK parameter: Systemic clearance (CL) | Within 5 cycles (each cycle is 28 days) | MHB088C, total antibody, free toxin MH30010008 |
| Immunogenicity Assessment | Within 5 cycles (each cycle is 28 days) | Assessment of anti-drug antibody (ADA) |
| Pharmacokinetics (PK) parameter: Maximum concentration (Cmax) | Within 5 cycles (each cycle is 28 days) | MHB088C, total antibody, free toxin MH30010008 |
| Duration of Response (DOR) | through study completion, an average of 1 year | DOR was defined as the time from first assessment of PR or CR until disease progression. |
| Disease Control Rate (DCR) | through study completion, an average of 1 year | DCR was defined as the proportion of participants with a complete response (CR), partial response (PR) or stable disease (SD). |
| Progression Free Survival (PFS) | through study completion, an average of 1 year | Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Objective Response Rate (ORR) | through study completion, an average of 1 year | Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) |
| PK parameter: Time to maximum concentration (Tmax) | Within 5 cycles (each cycle is 28 days) | MHB088C, total antibody, free toxin MH30010008 |
| PK parameter: Area under the concentration-time curve (AUC) | Within 5 cycles (each cycle is 28 days) | MHB088C, total antibody, free toxin MH30010008 |
Countries
Australia
Contacts
Primary ContactContact for Clinical Trial Information Minghui Pharmaceutical
Outcome results
None listed