Study of MC001 in Patients With Advanced Solid Tumours

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• Age ≥21 years at the time of informed consent
• Histology or cytology confirmation of advanced or metastatic solid tumour that is unresectable or refractory to standard therapy, or for which no standard therapy is available
• Tumour FRα expression, defined as:; Dose escalation: No predefined FRα expression level required for inclusion into dose escalation; Dose expansion: Moderate to high membranous FRα expression in ≥50% of tumour cells, as assessed by immunohistochemistry (IHC) using an assay validated for this study
• Tumour type eligibility:; Dose escalation: all solid tumours are eligible for escalation phase; Dose expansion: restricted to PDAC and NPC only
• Measurable disease per RECIST version 1.1
• Mandatory baseline tumour biopsy, obtained prior to first administration of MC001, unless deemed unsafe by the investigator
• ECOG performance status of 0 or 1
• Adequate organ and marrow function, defined as:; Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; Platelet count ≥100 × 10⁹/L; Haemoglobin ≥9.0 g/dL; Creatinine clearance ≥50 mL/min (Cockcroft-Gault); AST and ALT ≤3 × ULN (≤5 × ULN if liver metastases present); Total bilirubin ≤1.5 × ULN
• Baseline imaging feasibility, defined as:; Ability to undergo contrast-enhanced CT at baseline, or; MRI abdomen/pelvis with non-contrast CT thorax if contrast CT is contraindicated
• Recovered from prior therapy-related toxicities to:; o Grade ≤1 per CTCAE v6.0
• Life expectancy ≥12 weeks, as assessed by the investigator
• Women of childbearing potential (WOCBP) must:; Have a negative pregnancy test at screening; Agree to use highly effective contraception during the study and for 6 months after the last dose of MC001; Subjects not considered WOCBP are those without menses for ≥ 12 consecutive months, and those who have undergone hysterectomy and/or bilateral salpingo-oophorectomy. WOCBP must be willing to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of the study and 6 months after the last dose of treatment
• Male participants with partners of childbearing potential are required to use barrier contraception in addition to having their partner use another method of contraception during the study and for 6 months after the last dose of treatment. Male participants will also be advised to abstain from sexual intercourse with pregnant or lactating women, or to use condoms
• Ability to understand and voluntarily sign written informed consent

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• Prior exposure to MMAE-containing antibody-drug conjugates, or known hypersensitivity to MMAE or related compounds
• Known active central nervous system (CNS) metastases or carcinomatous meningitis, unless:; Previously treated; Clinically stable for ≥4 weeks; Not requiring corticosteroids >10 mg prednisolone (or equivalent) daily
• Receipt of any investigational study drug within 28 days or 5 half-lives (whichever is shorter) prior to the first administration of MC001
• Major surgery within 4 weeks prior to first administration of MC001
• Known uncontrolled viral infections, including:; Active hepatitis B or C with uncontrolled viral load; Known HIV infection with detectable viral load; *Hepatitis B virus (HBV):; Participants who are HBsAg positive are eligible provided that:; They have received antiviral therapy for HBV for at least 4 weeks prior to the first dose of MC001, and they have an undetectable HBV viral load at screening; Note: Participants must remain on HBV antiviral therapy throughout study treatment and follow local guidelines for continuation of antiviral therapy after completion of study treatment; Patients who are HBsAg negative, and anti-HB core total positive are not considered to have active hepatitis if HB viral load is undetectable; Hepatitis C virus (HCV):; Participants with a history of HCV infection are eligible provided that:; HCV viral load is undetectable at screening, and; Curative antiviral therapy was completed at least 12 weeks prior to initiation of study treatment; Participants with active, uncontrolled viral hepatitis not meeting the above criteria will be excluded
• Clinically significant ocular disease, including:; Active keratitis; Severe dry eye requiring ongoing ophthalmologic intervention; Corneal ulceration or other conditions that may increase ADC-related ocular risk
• Second active malignancy requiring treatment
• Any condition that, in the investigator's judgment, would place the participant at unacceptable risk or interfere with interpretation of study results
• Uncontrolled intercurrent illness, including but not limited to:; Active infection requiring systemic therapy; Symptomatic congestive heart failure or LVEF < 40% on screening echocardiogram; Unstable angina; Significant cardiac arrhythmia including QTc > 500ms; Psychiatric illness or social situations limiting compliance
• Participants meeting any of the following criteria will be excluded:
• Peripheral neuropathy ≥ Grade 2 at baseline
• Pregnant or breastfeeding women