A Phase I, Multicentre, Open-label, First-in-Human, Dose Escalation and Expansion Study of DM002 in Patients With Advanced Solid Tumors
The goal of study： The study has two parts: Part 1 Dose Escalation and Part 2 Dose Expansion. In Part 1, a few participants will receive the lowest dose of study drug. The study team will make sure it is safe and tolerated before enrolling new participants at a higher dose of study drug. There will be up to six or more dose levels of study drug tested (called cohorts). Which dose you receive will depend on how many participants have taken part in the study before you. The purpose of Part 1 of the study is to evaluate the safety of the study drug at different dose levels, to understand what your body does to the study drug, and to find the best dose of study drug in people who have advanced solid tumor cancers. In Part 2, participants will receive the best dose level that was determined in Part 1 of the study. The purpose of Part 2 of the study is to evaluate the safety of the study drug at the dose level determined in Part 1, to understand what your body does to the study drug, and to see how your cancer responds to the study drug. Participants will: Participants will have 17 or more visits to the study centre. This study has a screening phase of up to 28 days , and a treatment phase with cycles of 21 days each. Participants will also have an End of Treatment (EOT) visit 21 days after the final study drug treatment, and a Follow-up visit 30 days after the EOT visit . Participants will be contacted by telephone every 3 months after the Follow-up visit to check on the wellbeing and record any new anticancer therapy they may have started.
‣ Common Inclusion Criteria (Part 1 and Part 2)
• Subjects must have the ability to understand and willingness to sign a written informed consent document.
• Subjects must be ≥18 years of age at the time of signing the informed consent form.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Has a life expectancy of ≥3 months.
• Participants must meet the following laboratory values within 7 days prior to first dose of study drug:
• Note: Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 2 weeks prior to laboratory assessments at Screening.
⁃ Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L;
⁃ Platelet count ≥100 × 10⁹/L;
⁃ Hemoglobin ≥9 g/dL;
⁃ Calculated creatinine clearance (CrCL) \>60 mL/min (Cockroft-Gault Equation);
⁃ Total bilirubin ≤ 1.5 x ULN;
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × upper limit of normal (ULN), if liver metastases are present, ≤5 × ULN;
⁃ International normalized ratio (INR)\<2.0, and prothrombin time and either partial thromboplastin time (PTT) or activated PTT (aPTT) ≤1.5 × ULN, except for participants receiving anti-vitamin K derivative anticoagulant therapy who must have prothrombin time/INR within therapeutic range as deemed appropriate by the Investigator.
• Has measurable disease based on RECIST version 1.1.
• Participants are required to provide tumor tissue specimens obtained within the previous 3 years for the measurement of MUC1 and/or HER3 and other biomarkers. For those subjects who are unable to provide tissue samples will be encouraged (but not mandatory) to undergo biopsy if the risk is manageable. If the biopsy is not possible, it should inform the sponsor for enrolment.