Phase 1/2a Study of MPB-1734 in Patients With Advanced Solid Tumors

This study will occur in two parts, Dose-escalation (Part 1) and Cohort-expansion (Part 2). The main purpose of Part 1 is to determine the doses and dosing schedule of MPB-1734 that is safe and tolerable when given in subjects with certain types of advanced cancer. Part 2 of the study will begin when the Sponsor determines the safe and tolerable doses and dosing schedule from Part 1. The main purpose of Part 2 is to continue to assess the safety and tolerability of the MPB-1734 dose and dosing schedule determined by the Sponsor during Part 1. The preliminary efficacy of MPB-1734 will also be assessed in both Part 1 and Part 2.

Inclusion criteria

• Signed informed consent in the local language prior to any study-mandated procedure.
• Male or female patients at least 18 years of age, at the time of informed consent.
• Male or nonpregnant and nonlactating female patients with pathologically confirmed, measurable solid tumor lesions (Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]) that are unresectable, and standard therapy able to provide clinical benefit does not exist or is no longer effective.
• Eastern Cooperative Oncology Group Performance Status ≤2.
• Patients have recovered from the acute toxicity of previous therapies (peripheral sensory neuropathy recovered to ≤Grade 2) except alopecia, and:

• At least 4 weeks have elapsed since completing surgery, endocrine therapy, tyrosine kinase inhibitor therapy, immunotherapy, radiotherapy, chemotherapy, and/or
• At least 6 weeks have elapsed since completing chemotherapy with nitrosoureas, melphalan, and/or mitomycin C, and/or
• At least 6 weeks have elapsed since completing cranial radiotherapy.
• Life expectancy of greater than 12 weeks.
• Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.

Exclusion criteria

• Peripheral sensory neuropathy >Grade 2 (CTCAE version 5.0) at baseline.
• Patients requiring immediate palliative treatment of any kind including surgery and/or radiotherapy.
• Serum bilirubin >1.5× ULN.
• AST and/or ALT >2.5× ULN if no liver involvement, OR AST and/or ALT >5× ULN with liver involvement.
• Serum creatinine >1.5× ULN, and/or a creatinine clearance of <50 mL/min calculated by Cockcroft Gault.
• QTc prolongation defined as a QTc with Framingham correction greater than or equal to 470 ms, or significant electrocardiogram (ECG) abnormalities.
• Known hypersensitivity to taxanes or any excipients of the drug formulation.
• Female patients who are pregnant, breast-feeding, or planning to become pregnant during the study.
• Untreated and/or uncontrolled central nervous system metastases.
• Patients with brain tumors, primary or metastatic.
• Patients taking concomitant medications anticipated to result in drug-drug interactions.