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Study of MC001 in Patients With Advanced Solid Tumours

4. november 2026 oppdatert av: National University Hospital, Singapore

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.

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

This is a first-in-human, open-label, Phase I clinical trial evaluating MC001 administered as monotherapy via intravenous infusion every 21 days (Q3W) in patients with advanced folate receptor-expressing solid tumours. Each treatment cycle is defined as 21 days.

The study comprises two sequential components: a Dose Escalation Phase followed by a Dose Expansion Phase. During dose escalation, the mTPI-2 method will be used to determine the appropriate dose across 7 dose levels. Following completion of dose escalation, expansion cohorts will enrol patients with PDAC and NPC at the recommended dose for expansion (RDE) to further evaluate safety and preliminary antitumour activity.

Studietype

Intervensjonell

Registrering (Antatt)

80

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Singapore
      • Singapore, Singapore, 119228
        • National University Cancer Institute Singapore
        • Ta kontakt med:
        • Ta kontakt med:
        • Hovedetterforsker:
          • Robert J Walsh, Medical Degree
        • Underetterforsker:
          • Boon Cher Goh, Medical Degree

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

21 år til 99 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Age ≥21 years at the time of informed consent.

  2. 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.

  3. 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.

  4. Tumour type eligibility:

    • Dose escalation: all solid tumours are eligible for escalation phase.
    • Dose expansion: restricted to PDAC and NPC only.

  5. Measurable disease per RECIST version 1.1.

  6. Mandatory baseline tumour biopsy, obtained prior to first administration of MC001, unless deemed unsafe by the investigator.

  7. ECOG performance status of 0 or 1.

  8. 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

  9. 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.

  10. Recovered from prior therapy-related toxicities to:

    o Grade ≤1 per CTCAE v6.0

  11. Life expectancy ≥12 weeks, as assessed by the investigator.

  12. 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.

  13. 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.

  14. Ability to understand and voluntarily sign written informed consent.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded:

  1. Prior exposure to MMAE-containing antibody-drug conjugates, or known hypersensitivity to MMAE or related compounds.

  2. Peripheral neuropathy ≥ Grade 2 at baseline.

  3. 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.

  4. 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.

  5. 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.

  6. Receipt of any investigational study drug within 28 days or 5 half-lives (whichever is shorter) prior to the first administration of MC001.

  7. Major surgery within 4 weeks prior to first administration of MC001.

  8. Pregnant or breastfeeding women.

  9. 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:

      1. HCV viral load is undetectable at screening, and

      2. 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

  10. Second active malignancy requiring treatment.

  11. Any condition that, in the investigator's judgment, would place the participant at unacceptable risk or interfere with interpretation of study results.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Sekvensiell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Dose Level 1

0.3 mg/kg
Legemiddel: MC001

MC001 will be administered as an intravenous infusion once every 21 days at the dose level and schedule assigned per protocol. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or at the discretion of the investigator. MC001 is supplied by Medicovestor, Inc.
Eksperimentell: Dose Level 2

0.6 mg/kg
Legemiddel: MC001

MC001 will be administered as an intravenous infusion once every 21 days at the dose level and schedule assigned per protocol. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or at the discretion of the investigator. MC001 is supplied by Medicovestor, Inc.
Eksperimentell: Dose Level 3

1.0 mg/kg
Legemiddel: MC001

MC001 will be administered as an intravenous infusion once every 21 days at the dose level and schedule assigned per protocol. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or at the discretion of the investigator. MC001 is supplied by Medicovestor, Inc.
Eksperimentell: Dose Level 4

1.6 mg/kg
Legemiddel: MC001

MC001 will be administered as an intravenous infusion once every 21 days at the dose level and schedule assigned per protocol. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or at the discretion of the investigator. MC001 is supplied by Medicovestor, Inc.
Eksperimentell: Dose Level 5

2.2 mg/kg
Legemiddel: MC001

MC001 will be administered as an intravenous infusion once every 21 days at the dose level and schedule assigned per protocol. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or at the discretion of the investigator. MC001 is supplied by Medicovestor, Inc.
Eksperimentell: Dose Level 6

2.8 mg/kg
Legemiddel: MC001

MC001 will be administered as an intravenous infusion once every 21 days at the dose level and schedule assigned per protocol. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or at the discretion of the investigator. MC001 is supplied by Medicovestor, Inc.
Eksperimentell: Dose Level 7

3.2 mg/kg
Legemiddel: MC001

MC001 will be administered as an intravenous infusion once every 21 days at the dose level and schedule assigned per protocol. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or at the discretion of the investigator. MC001 is supplied by Medicovestor, Inc.
Eksperimentell: Dose Expansion - PDAC

MC001 at the recommended dose for expansion (RDE), in patients with FRα-positive PDAC.
Legemiddel: MC001

MC001 will be administered as an intravenous infusion once every 21 days at the dose level and schedule assigned per protocol. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or at the discretion of the investigator. MC001 is supplied by Medicovestor, Inc.
Eksperimentell: Dose Expansion - NPC

MC001 at the RDE, in patients with FRα-positive NPC.
Legemiddel: MC001

MC001 will be administered as an intravenous infusion once every 21 days at the dose level and schedule assigned per protocol. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or at the discretion of the investigator. MC001 is supplied by Medicovestor, Inc.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Incidence of Adverse Events (AEs)
Tidsramme: From informed consent until 30 days after the last dose of MC001 (approximately 2 years)

Incidence and severity of adverse events (AEs) occurring during the study period, assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0. CTCAE grades range from Grade 1 (mild) to Grade 5 (death related to an adverse event).
From informed consent until 30 days after the last dose of MC001 (approximately 2 years)
Incidence of Serious Adverse Events (SAEs)
Tidsramme: From screening until end of treatment (up to approximately 2 years)

Number of participants experiencing one or more serious adverse events (SAEs) during the study period.
From screening until end of treatment (up to approximately 2 years)
Incidence of dose-limiting toxicities
Tidsramme: During Cycle 1 (21 days)

Number of participants experiencing a dose-limiting toxicity (DLT) during Cycle 1. DLTs are protocol-defined adverse events occurring during the first 21 days of treatment that are considered at least possibly related to the study drug and are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0.
During Cycle 1 (21 days)
Maximum Tolerated Dose (MTD)
Tidsramme: From first dose until completion of dose escalation (up to approximately 24 months)

The maximum tolerated dose (MTD) is determined using the modified Toxicity Probability Interval (mTPI-2) design and is defined as the highest dose level at which the observed rate of dose-limiting toxicities (DLTs) during Cycle 1 does not exceed the prespecified target toxicity probability.
From first dose until completion of dose escalation (up to approximately 24 months)
Maximum Administered Dose (MAD)
Tidsramme: From first dose until completion of dose escalation (up to approximately 24 months)

The maximum administered dose (MAD) is determined as the highest dose level of MC001 evaluated during the dose-escalation phase, regardless of whether a maximum tolerated dose (MTD) is reached.
From first dose until completion of dose escalation (up to approximately 24 months)
Recommended Dose for Expansion (RDE)
Tidsramme: From first dose until determination of the recommended dose for expansion (approximately 6 to 12 months)

The recommended dose for expansion (RDE) is selected for evaluation in the expansion cohorts based on an integrated assessment of dose-limiting toxicities (DLTs), overall safety and tolerability, pharmacokinetic data, and preliminary evidence of antitumour activity. The RDE may be equal to or lower than the maximum tolerated dose (MTD).
From first dose until determination of the recommended dose for expansion (approximately 6 to 12 months)

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression-Free Survival (PFS)
Tidsramme: From first dose until documented disease progression or death from any cause, up to approximately 2 years

Progression-free survival (PFS), defined as the time from first dose of MC001 to documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
From first dose until documented disease progression or death from any cause, up to approximately 2 years
Overall Survival (OS)
Tidsramme: From first dose until death from any cause, up to approximately 2 years

Overall survival (OS), defined as the time from first dose of MC001 to death from any cause.
From first dose until death from any cause, up to approximately 2 years
Maximum Observed Plasma Concentration (Cmax) of MC001
Tidsramme: From pre-dose until end of treatment (up to approximately 2 years)

Maximum observed plasma concentration (Cmax) of conjugated ADC, total antibody, and unconjugated monomethyl auristatin E (MMAE) following administration of MC001.
From pre-dose until end of treatment (up to approximately 2 years)
Changes in ADCC Activity
Tidsramme: From baseline until end of treatment (up to approximately 2 years)

Changes from baseline in antibody-dependent cellular cytotoxicity (ADCC) activity assessed using protocol-defined immune correlative analyses of peripheral blood samples collected during treatment.
From baseline until end of treatment (up to approximately 2 years)
Objective Response Rate (ORR)
Tidsramme: From first dose until disease progression, withdrawal, or end of treatment (up to approximately 2 years)

Objective response rate (ORR), defined as the proportion of participants achieving a best overall response of complete response (CR) or partial response (PR) according to RECIST version 1.1.
From first dose until disease progression, withdrawal, or end of treatment (up to approximately 2 years)
Change From Baseline in Serum CA19-9
Tidsramme: From baseline until end of treatment (up to approximately 2 years)

Change from baseline in serum carbohydrate antigen 19-9 (CA19-9) levels as a predefined blood-based biomarker to characterise the pharmacodynamic effects of MC001.
From baseline until end of treatment (up to approximately 2 years)
Change From Baseline in Plasma Epstein-Barr Virus DNA
Tidsramme: From baseline until end of treatment (up to approximately 2 years)

Change from baseline in plasma Epstein-Barr virus (EBV) DNA levels as a predefined blood-based biomarker to characterise the pharmacodynamic effects of MC001.
From baseline until end of treatment (up to approximately 2 years)
Change From Baseline in Serum CA-125
Tidsramme: From baseline until end of treatment (up to approximately 2 years)

Change from baseline in serum cancer antigen 125 (CA-125) levels as a predefined blood-based biomarker to characterise the pharmacodynamic effects of MC001.
From baseline until end of treatment (up to approximately 2 years)
Change From Baseline in Carcinoembryonic Antigen
Tidsramme: From baseline until end of treatment (up to approximately 2 years)

Change from baseline in serum carcinoembryonic antigen (CEA) levels as a predefined blood-based biomarker to characterise the pharmacodynamic effects of MC001.
From baseline until end of treatment (up to approximately 2 years)
Time to Maximum Observed Plasma Concentration (Tmax) of MC001
Tidsramme: From pre-dose until end of treatment (up to approximately 2 years)

Time to reach maximum observed plasma concentration (Tmax) of conjugated ADC, total antibody, and unconjugated monomethyl auristatin E (MMAE) following administration of MC001.
From pre-dose until end of treatment (up to approximately 2 years)
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of MC001
Tidsramme: From pre-dose until end of treatment (up to approximately 2 years)

Area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-last) for conjugated ADC, total antibody, and unconjugated monomethyl auristatin E (MMAE).
From pre-dose until end of treatment (up to approximately 2 years)
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUCτ) of MC001
Tidsramme: From pre-dose until end of treatment (up to approximately 2 years)

Area under the plasma concentration-time curve over the dosing interval (AUCτ) for conjugated ADC, total antibody, and unconjugated monomethyl auristatin E (MMAE).
From pre-dose until end of treatment (up to approximately 2 years)
Terminal Elimination Half-life (t½) of MC001
Tidsramme: From pre-dose until end of treatment (up to approximately 2 years)

Terminal elimination half-life (t½), where estimable, of conjugated ADC, total antibody, and unconjugated monomethyl auristatin E (MMAE).
From pre-dose until end of treatment (up to approximately 2 years)
Trough Plasma Concentration (Ctrough) of MC001
Tidsramme: From pre-dose until end of treatment (up to approximately 2 years)

Trough plasma concentration (Ctrough) of conjugated ADC, total antibody, and unconjugated monomethyl auristatin E (MMAE).
From pre-dose until end of treatment (up to approximately 2 years)
Accumulation Ratio (C4/C1) of MC001
Tidsramme: From pre-dose until end of treatment (up to approximately 2 years)

Accumulation ratio based on plasma concentration following Cycle 4 and Cycle 1 dosing (C4/C1) for conjugated ADC, total antibody, and unconjugated monomethyl auristatin E (MMAE).
From pre-dose until end of treatment (up to approximately 2 years)

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

National University Hospital, Singapore

Samarbeidspartnere

Medicovestor, Inc

Etterforskere

  • Hovedetterforsker: Robert J Walsh, Medical Degree, National University Hospital, Singapore

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

16. november 2026

Primær fullføring (Antatt)

30. november 2030

Studiet fullført (Antatt)

30. november 2031

Datoer for studieregistrering

Først innsendt

25. oktober 2026

Først innsendt som oppfylte QC-kriteriene

4. november 2026

Først lagt ut (Faktiske)

10. november 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

10. november 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

4. november 2026

Sist bekreftet

1. november 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • PA01/02/26
  • CTA2600101 (Annen identifikator: Health Sciences Authority)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

UBESLUTTE

IPD-planbeskrivelse

A decision on whether to share Individual Participant Data (IPD) has not yet been made at this stage of the study.

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

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