Advanced Solid Tumor
Conditions
Brief summary
This study will evaluate the safety, pharmacokinetics, and anti-tumor efficacy of MHB036C in participants with advanced or metastatic solid tumors.
Detailed description
This study is the first-in-human (FIH) trial of MHB036C, and contains two parts: dose escalation phase (part one) and dose expansion phase (part two). The dose escalation phase is an open-label, multi-center study in which eligible participants with advanced or metastatic solid tumors will be enrolled to receive MHB036C monotherapy. This study is designed to assess the safety and tolerability of MHB036C in participants with advanced or metastatic solid tumors, to determine the maximum tolerated dose (MTD) of MHB036C, 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 MHB036C monotherapy. Participants with same types of solid tumors will be randomized assigned 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 MHB036C monotherapy in subjects 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 MHB036C.
Interventions
DRUGMHB036C
MHB036C will be administered intravenously at a frequency of once every 3 weeks (Q3W).
Sponsors
Minghui Pharmaceutical Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single group, but in two study parts, therefore two sequential arms are identified
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 (ICF). 2. Participants aged 18 years or older (inclusive), without gender limitation. 3. Participants with ECOG performance score of 0 \ 1. 4. Participants with expected survival time of more than 3 months. 5. Eligible participants of childbearing potential (males and females) must agree to take 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; female participants of childbearing potential must have a negative results of blood pregnancy test within 7 days before the first dose of the investigational product, and must be non-lactating. 6. Participants who are able to understand study requirements, and willing and able to comply with arrangements of study and follow-up procedures. Neoplasm-related criteria 7. Participants to be enrolled in part one must have histologically or cytologically confirmed advanced or metastatic solid tumors, which have failed or are intolerant to standard of care (SOC), or for which no SOC is available; 8. Participants to be enrolled in part two must have histologically or cytologically confirmed advanced or metastatic solid tumors, including but not limited to the following types: non-small cell lung cancer (NSCLC); small cell lung cancer (SCLC); pancreatic ductal adenocarcinoma (PDAC); head and neck squamous cell carcinoma (HNSCC); esophageal squamous cell carcinoma (ESCC); urothelial carcinoma (UC); ovarian cancer (OC); endometrial cancer (EC); breast cancer (BC); gastric cancer (GC); castration-resistant prostate cancer (CRPC); sweat gland carcinoma (SGC). 1. Additional criteria for enrollment of participants with NSCLC: * Participants with unresectable advanced NSCLC who have failed standard of care with platinum doublet chemotherapy and immune-checkpoint inhibitors (ICIs), and are not suitable for radical therapy (NSCLC participants with driver gene mutations should have failed or are intolerant to targeted therapy for the corresponding driver gene mutation, or unsuitable for the corresponding targeted therapy as per investigator's evaluation ). 2. Additional criteria for enrollment of participants with SCLC: * Participants with unresectable or metastatic SCLC who have previously received at least one line of systemic chemotherapy, including platinum-based chemotherapy and immune-checkpoint inhibitors (ICIs) 3. Additional criteria for enrollment of participants with PDAC: * Participants with unresectable or metastatic PDAC who have previously received at least one line of systemic chemotherapy, including any stage in neoadjuvant/adjuvant/ palliative therapy 4. Additional criteria for enrollment of participants with HNSCC: * Participants with unresectable advanced or metastatic HNSCC who have previously received at least one line of systemic chemotherapy, including platinum-based chemotherapy and ICIs (combined or sequential therapy). 5. Additional criteria for enrollment of participants with ESCC: * Participants with unresectable or metastatic ESCC who have previously received at least one line of systemic chemotherapy (platinum-based chemotherapy). 6. Additional criteria for enrollment of participants with UC: * Participants with unresectable, locally progressed, or metastatic (histologically including transitional cells and mixed of transitional/non-transitional cells) UC (sites of occurrence including renal pelvis, ureter, bladder, and urethra) who have previously received at least one line of chemotherapy, including platinum-based chemotherapy and ICIs (combined or sequential therapy). 7. Additional criteria for enrollment of participants with OC: * Participants with OC (including rare types of epithelial ovarian cancer stipulated in the NCCN guidelines as well as fallopian tube cancer and primary peritoneal cancer) who had tumor recurrence or metastasis after receiving at least one line of platinum-based chemotherapy 8. Additional criteria for enrollment of participants with EC: * Participants with recurrent or incurable EC who had tumor recurrence or progression following previous radical therapy, and subsequently received therapies including standard systemic therapy. 9. Additional criteria for enrollment of participants with BC: * For participants with advanced/unresectable or metastatic TNBC: Participants who have received at least 1 line of systemic chemotherapy with anthracyclines and taxanes included in the prior systemic therapy (regardless of neoadjuvant/adjuvant/palliative therapy). * For BC participants with hormone receptor (HR) positive (ER+ and/or PR+) and HER2 expression negative (IHC 0, 1+ or IHC 2+ with ISH-): Participants who are intolerant or resistant to endocrine therapy, or unsuitable for endocrine therapy as per investigator's evaluation. * For BC participants with HER2 expression positive (IHC 3+ or IHC 2+ with ISH+): Participants who have previously received at least 1 line of therapy, which included HER2-targeted therapy. 10. Additional criteria for enrollment of participants with GC: * Participants with unresectable or metastatic GC who have previously received at least one line of standard systemic chemotherapy, while the previous treatment regimens of HER2-positive (IHC 3+ or IHC 2+ with ISH+) participants must include HER2-targeted therapy. 11. Additional criteria for enrollment of participants with CRPC: * Absence of neuroendocrine differentiation or small cell histology confirmed by histopathology; * Underwent surgical or medical castration, with testosterone levels below 50 ng/dL; * Objective progression as determined by radiographic progression after androgen deprivation therapy; * Participants has relapsed or progressed after receiving at least one of the following medications: abiraterone, enzalutamide, apalutamide, or darolutamide; * Participants has relapsed or progressed after previously docetaxel-based or mitoxantrone-based cytotoxic chemotherapy for metastatic CRPC; * Participants with at least 1 documented lesion confirmed by either a bone scan or a CT/MRI scan. 12. Sweat gland carcinoma (SGC): unresectable or metastatic SGC. 9. Participants who agree to provide the pre-treatment tumor tissue samples for retrospective testing of target expression and other biomarkers (participants who agree but are unable to provide pre-treatment tumor tissue sample may also be enrolled). Expression of target in tumor tissue samples collected from participants will not be used as a criterion for participant enrollment. 10. Participants with at least one measurable tumor lesion as per RECIST v1.1 (generally, tumor lesions located in a previously irradiated areas or other locoregional treatment sites will not be considered as measurable lesions, unless the lesions have clearly progressed or still persist three months after radiotherapy); for participants with CRPC, evaluable lesions as defined by PCWG3 criteria, or at least one measurable tumor lesion as per RECIST v1.1 are required. Adequate bone marrow reserve and organ functions: 11. Adequate bone marrow reserve (without transfusion, treatment of colony-stimulating factor, or biologics with similar effects within 7 days prior to the screening); * Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; * Platelet count ≥ 100 × 109/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 ≤ 2.0 × ULN if Gilbert's syndrome is present; TBIL ≤ 3.0 × ULN is permitted if direct bilirubin (DBIL) suggests extrahepatic obstruction. * For participants with non-hepatic tumors and without hepatic metastases, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) shall be ≤ 3.0 × ULN; for participants with hepatic tumors or hepatic metastases, AST and ALT shall be ≤ 5.0 × ULN; 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. 15. Adequate cardiac function: * Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram within 28 days prior to 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 |
|---|---|---|
| Number of participants with adverse events | From the day of the first dose of MHB036C to 30 days after the day of the last dose of MHB036C | Adverse events was assessed by investigator(s) according to NCI-CTCAE v5.0 |
| Number of participants with dose-limiting toxicities | 21 days after the first dose of MHB036C | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameter: Area under the concentration-time curve (AUC) | Within 5 cycles (each cycle is 21 days) | Categories: MHB036C, total antibody, free toxin MH30010008 |
| PK parameter: Trough concentration (Ctrough) | Within 5 cycles (each cycle is 21 days) | Categories: MHB036C, total antibody, free toxin MH30010008 |
| PK parameter: Terminal or apparent terminal half-life (t1/2) | Within 5 cycles (each cycle is 21 days) | Categories: MHB036C, total antibody, free toxin MH30010008 |
| PK parameter: Systemic clearance (CL) | Within 5 cycles (each cycle is 21 days) | Categories: MHB036C, total antibody, free toxin MH30010008 |
| Pharmacokinetics (PK) parameter: Maximum concentration (Cmax) | Within 5 cycles (each cycle is 21 days) | Categories: MHB036C, total antibody, free toxin MH30010008 |
| Objective Response Rate (ORR) | 24 months | Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) |
| Duration of Response (DOR) | 24 months | DOR was defined as the time from first assessment of PR or CR until disease progression. |
| Disease Control Rate (DCR) | 24 months | DCR was defined as the proportion of participants with a complete response (CR), partial response (PR) or stable disease (SD). |
| Progression Free Survival (PFS) | 24 months | 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. |
| Immunogenicity Assessment | Within 5 cycles (each cycle is 21 days) | Assessment of anti-drug antibody (ADA) |
| PK parameter: Time to maximum concentration (Tmax) | Within 5 cycles (each cycle is 21 days) | Categories: MHB036C, total antibody, free toxin MH30010008 |
Countries
Australia
Contacts
Primary ContactMinghui Pharmaceutical Contact for Clinical Trial Information
Outcome results
None listed