- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT07909356
A Study of MC001 in Patients With Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) and Other Folate Receptor Alpha (FRα)-Expressing Solid Tumors
A First-in-Human, Open-Label, Multicenter, Phase 1, Dose Escalation Study With Cohort Expansion to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of MC001, a Dimeric Antibody-Drug Conjugate (ADC), in Patients With Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) and Other Solid Tumors Expressing Folate Receptor Alpha (FRα)
The purpose of this First-in-Human, Phase 1 study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity of MC001 in adults with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) and other solid tumors that have relapsed or are refractory to standard therapies. MC001 is an investigational dimeric antibody-drug conjugate (ADC) that targets folate receptor alpha (FRα) and delivers a microtubule-disrupting cytotoxic payload, monomethyl auristatin E (MMAE).
The study will be conducted in two sequential parts:
Part A (Dose Escalation): Evaluates ascending intravenous (IV) dose levels of MC001 administered once every 3 weeks (Q3W) using a standard 3+3 design in patients with advanced solid tumors to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), and the recommended dose for expansion (RDE).
Part B (Dose Expansion): Evaluates MC001 at the selected RDE in patients with advanced or metastatic PDAC whose tumors express FRα on at least 30% of tumor cells to further characterize safety and preliminary efficacy.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Melissa Askin, MS, BSN, CCRP
- Número de telefone: 410-231-1512
- E-mail: melissa.askin@acroclinical.com
Locais de estudo
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New York
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Syracuse, New York, Estados Unidos, 13210
- SUNY Upstate Medical University
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North Carolina
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Huntersville, North Carolina, Estados Unidos, 28078
- Carolina BioOncology Institute, PLLC
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Texas
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San Antonio, Texas, Estados Unidos, 78229
- NEXT Oncology
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Virginia
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Fairfax, Virginia, Estados Unidos, 22031
- NEXT Oncology
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
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Age 18 years or older.
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Histologically and radiologically confirmed advanced surgically unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) or other solid tumors.
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Folate Receptor alpha (FRα) expression determined by immunohistochemistry (IHC) at a central laboratory:
- Part A (Phase 1a Dose Escalation): FRα expression status will be assessed primarily for pharmacodynamic evaluation (not required for enrollment).
- Part B (Phase 1b Dose Expansion): FRα expression must be documented on the cell surface in at least 30% of PDAC tumor cells prior to enrollment.
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Failed at least one prior line of systemic chemotherapy. If daraxonrasib is accessible to the patient, the patient must have failed at least one line of systemic chemotherapy and prior treatment with daraxonrasib.
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Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
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Adequate organ and bone marrow function:
- Hematologic: Absolute neutrophil count (ANC) >= 1.5 x 10^9/L, platelets >= 100 x 10^9/L, hemoglobin >= 9 g/dL.
- Hepatic: Total bilirubin <= 1.5 x upper limit of normal (ULN); ALT and AST <= 2.5 x ULN (or <= 5 x ULN in case of liver involvement).
- Renal: Creatinine clearance >= 60 mL/min calculated by Cockcroft-Gault formula.
- Coagulation: Prothrombin time (PT)/International Normalized Ratio (INR) <= 1.5 x ULN.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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Estimated life expectancy >= 3 months per investigator's assessment.
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Female patients must not be pregnant or breastfeeding, and must be either not of childbearing potential or agree to use highly effective contraception from 1 month before study start through 6 months after completion of study treatment. Male patients with partners of childbearing potential must agree to use highly effective contraception during the study and for up to 6 months after the last dose.
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Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram, and Fridericia-corrected QT interval (QTcF) < 470 ms for both sexes.
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Availability of archival or fresh tumor tissue for biomarker analysis.
Exclusion Criteria:
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Prior exposure to antibody-drug conjugates (ADCs) targeting FRα or conjugated to monomethyl auristatin E (MMAE).
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History of allergy to immunoglobulins or MMAE.
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Receipt of radiation therapy <= 14 days before Cycle 1 Day 1, or failure to recover to Grade <= 1 from treatment-related side effects.
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Symptomatic central nervous system (CNS) malignancy. (Patients with asymptomatic or treated CNS metastases may be eligible if not receiving corticosteroids or anticonvulsants and disease is stable for >= 60 days).
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Peripheral sensory neuropathy Grade >= 2.
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Active infection, including Human Immunodeficiency Virus (HIV), requiring systemic therapy within <= 7 days prior to Cycle 1 Day 1.
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Active, uncontrolled Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection:
- HBsAg-positive patients are eligible if they have received HBV antiviral therapy for >= 4 weeks prior to first dose, have an undetectable HBV viral load at screening, and remain on antiviral therapy throughout the study.
- HBsAg-negative, anti-HBc total positive patients are eligible if HBV viral load is undetectable.
- Patients with a history of HCV infection are eligible if HCV viral load is undetectable at screening and curative antiviral therapy was completed >= 12 weeks prior to study treatment.
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History of major ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsades de Pointes [TdP]).
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Major surgical intervention <= 28 days prior to Informed Consent Form (ICF) signature or incomplete wound healing after surgery.
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Vaccination with a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention.
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Pregnancy or lactation.
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Unable or unwilling to sign the ICF, or patient is incarcerated.
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Refractory hypokalemia, congenital long QT syndrome, or family history of long QT syndrome; implantable pacemakers or automatic implantable cardioverter defibrillators; unstable angina requiring treatment; clinically significant bradycardia (<50 beats/min), tachycardia (>100 beats/min), or clinically significant ECG abnormalities; or use of drugs with a known risk of causing Torsades de Pointes (TdP) or QT interval prolongation within 4 weeks prior to the first dose.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Part A: MC001 Dose Escalation (Phase 1a)
Patients with advanced or metastatic PDAC or other solid tumors will receive escalating doses of MC001 administered via intravenous (IV) infusion once every 21 days (Q3W) following a 3+3 design across 5 planned dose levels: Dose Level 1 (0.3 mg/kg), Dose Level 2 (0.6 mg/kg), Dose Level 3 (1.0 mg/kg), Dose Level 4 (1.6 mg/kg), and Dose Level 5 (2.2 mg/kg). Treatment continues until disease progression, unacceptable toxicity, or withdrawal. |
Dimeric fully human IgG1 monoclonal antibody targeting Folate Receptor alpha (FRα) conjugated to Monomethyl Auristatin E (MMAE) via a protease-cleavable linker. Administered as an IV infusion once every 21 days (Q3W) following premedication with dexamethasone, diphenhydramine, acetaminophen, and a 5-HT3 antagonist. |
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Experimental: Part B: MC001 Dose Expansion in PDAC (Phase 1b)
Approximately 12 patients with advanced or metastatic PDAC with documented FRα expression in ≥30% of tumor cells will receive MC001 at the Recommended Dose for Expansion (RDE) determined in Part A, administered via IV infusion once every 21 days (Q3W) until disease progression, unacceptable toxicity, or withdrawal. |
Dimeric fully human IgG1 monoclonal antibody targeting Folate Receptor alpha (FRα) conjugated to Monomethyl Auristatin E (MMAE) via a protease-cleavable linker. Administered as an IV infusion once every 21 days (Q3W) following premedication with dexamethasone, diphenhydramine, acetaminophen, and a 5-HT3 antagonist. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Prazo: From first dose of study drug through 30 days after the last dose (up to approximately 36 months)
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Incidence and severity of AEs and SAEs, including clinically significant changes in laboratory parameters, vital signs, and ECGs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 6.0. |
From first dose of study drug through 30 days after the last dose (up to approximately 36 months)
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Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) in Part A (Dose Escalation)
Prazo: Cycle 1 (Day 1 to Day 21)
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A DLT is defined as any protocol-specified treatment-related hematologic, non-hematologic, or cardiac (QTcF) toxicity graded per NCI CTCAE v6.0 occurring during the DLT evaluation period. The incidence of DLTs in Cycle 1 is used to determine the Maximum Tolerated Dose (MTD, defined as the highest dose level at which ≤1 of 6 participants experiences a DLT) and Recommended Dose for Expansion (RDE). |
Cycle 1 (Day 1 to Day 21)
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) of MC001 (ADC), Total Antibody, and Unconjugated MMAE
Prazo: Cycle 1 (Days 1, 2, 8, and 15) and Day 1 of subsequent 21-day cycles (up to approximately 36 months)
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Plasma Cmax derived from intensive blood sampling in Cycle 1 and sparse sampling in subsequent cycles. |
Cycle 1 (Days 1, 2, 8, and 15) and Day 1 of subsequent 21-day cycles (up to approximately 36 months)
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Area Under the Plasma Concentration-Time Curve (AUC) of MC001 (ADC), Total Antibody, and Unconjugated MMAE
Prazo: Cycle 1 (Days 1, 2, 8, and 15) and Day 1 of subsequent 21-day cycles (up to approximately 36 months)
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Plasma AUC derived from pharmacokinetic blood sampling. |
Cycle 1 (Days 1, 2, 8, and 15) and Day 1 of subsequent 21-day cycles (up to approximately 36 months)
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Terminal Elimination Half-Life (T1/2) of MC001 (ADC), Total Antibody, and Unconjugated MMAE
Prazo: Cycle 1 (Day 1 through Day 15)
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Terminal half-life calculated from plasma concentration-time profiles during Cycle 1. |
Cycle 1 (Day 1 through Day 15)
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Objective Response Rate (ORR)
Prazo: From first dose of study drug until disease progression or treatment discontinuation (assessed prior to Cycles 3 and 5, and every 3 cycles thereafter, up to approximately 36 months)
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Proportion of participants in the response-evaluable analysis set achieving a confirmed Complete Response (CR) or Partial Response (PR) as determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
From first dose of study drug until disease progression or treatment discontinuation (assessed prior to Cycles 3 and 5, and every 3 cycles thereafter, up to approximately 36 months)
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Duration of Response (DoR)
Prazo: From date of first documented CR or PR until disease progression or death (up to approximately 36 months)
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Time from the date of first documented confirmed objective response (CR or PR) to the date of first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first. |
From date of first documented CR or PR until disease progression or death (up to approximately 36 months)
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Disease Control Rate (DCR)
Prazo: From first dose of study drug until disease progression or treatment discontinuation (up to approximately 36 months)
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Proportion of participants achieving CR, PR, or Stable Disease (SD, maintained for ≥6 weeks from start of treatment) as their best overall response per RECIST v1.1. |
From first dose of study drug until disease progression or treatment discontinuation (up to approximately 36 months)
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Progression-Free Survival (PFS)
Prazo: From first dose of study drug until disease progression or death (up to approximately 36 months)
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Time from the date of the first dose of MC001 to the date of first documented progressive disease per RECIST v1.1 or death due to any cause, whichever occurs first. |
From first dose of study drug until disease progression or death (up to approximately 36 months)
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Overall Survival (OS)
Prazo: From first dose of study drug until death from any cause (up to approximately 36 months)
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Time from the date of the first dose of MC001 to the date of death due to any cause. |
From first dose of study drug until death from any cause (up to approximately 36 months)
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Percentage of Participants With Anti-Drug Antibodies (ADAs) to MC001
Prazo: Screening, Cycle 1 (Days 1, 8, 15), Cycle 2 Day 1, Cycle 3 Day 1, every 2nd cycle thereafter, End of Treatment, and 30 and 90 days post-last dose (up to approximately 36 months)
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Incidence and persistence of treatment-emergent anti-drug antibodies (ADAs) evaluated via a tiered analytical approach (screening, confirmatory, and titer assays). |
Screening, Cycle 1 (Days 1, 8, 15), Cycle 2 Day 1, Cycle 3 Day 1, every 2nd cycle thereafter, End of Treatment, and 30 and 90 days post-last dose (up to approximately 36 months)
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Concentration-QTc Relationship: Change From Baseline in Fridericia-Corrected QT Interval (ΔQTcF)
Prazo: Cycle 1 (Day 1 pre-dose through 24 hours post-infusion, Day 8, and Day 14), Cycle 3 Day 1, and Cycle 6 Day 1
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Relationship between plasma MC001 concentrations and change from baseline in QTcF (ΔQTcF) evaluated via continuous Holter ECG monitoring paired with time-matched PK sampling. |
Cycle 1 (Day 1 pre-dose through 24 hours post-infusion, Day 8, and Day 14), Cycle 3 Day 1, and Cycle 6 Day 1
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Seah H Lim, MD, PhD, Medicovestor, Inc
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- MC001-101
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Individual participant data will not be shared publicly due to patient privacy and confidentiality considerations in a small Phase 1 first-in-human study.
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