Study of MC001 in Patients With Advanced Solid Tumours

Trial details

Who runs it

National University Hospital, Singapore

Trial code

NCT07929961

Record updated

2026. november 10.

Original description

The goal of this clinical trial is to evaluate the safety and tolerability of MC001 and to determine the appropriate dose for further development in adults with advanced solid tumours, with expansion cohorts in pancreatic ductal adenocarcinoma (PDAC) and nasopharyngeal carcinoma (NPC). The main questions it aims to answer are:Read full original descriptionShow less

Phase I First-in-Human Study of MC001 (ADoBind Dimeric IgG-Monomethyl Auristatin E), a First-in-Class Dimeric Antibody-Drug Conjugate Targeting Folate Receptor Alpha (FRα), in Patients With Advanced Solid Tumours

The goal of this clinical trial is to evaluate the safety and tolerability of MC001 and to determine the appropriate dose for further development in adults with advanced solid tumours, with expansion cohorts in pancreatic ductal adenocarcinoma (PDAC) and nasopharyngeal carcinoma (NPC). The main questions it aims to answer are:

* What is the maximum tolerated dose (MTD), maximum administered dose (MAD), and recommended dose for expansion (RDE) of MC001? * How does MC001 behave in the body following single and multiple doses? * Does MC001 show preliminary antitumour activity in patients with PDAC and NPC? * What are the pharmacodynamic effects of MC001? * What medical problems do participants have when taking MC001?

Research participants will:

* Receive MC001 every 21 days until disease progression, unacceptable toxicity, withdrawal of consent, or at the investigator's discretion. * Visit the clinic every 21 days for drug administration, biopsy, and assessments including blood tests, eye tests, and imaging.

Inclusion: 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.

Exclusion: 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.

ClinicalTrials.gov NCT07929961