A Study of MC001 in Patients With Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) and Other Folate Receptor Alpha (FRα)-Expressing Solid Tumors

Korábbi kezelés

• Prior exposure to antibody-drug conjugates (ADCs) targeting FRα or conjugated to monomethyl auristatin E (MMAE).
• Receipt of radiation therapy <= 14 days before Cycle 1 Day 1, or failure to recover to Grade <= 1 from treatment-related side effects.
• 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).
• Active infection, including Human Immunodeficiency Virus (HIV), requiring systemic therapy within <= 7 days prior to Cycle 1 Day 1.
• 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.
• Major surgical intervention <= 28 days prior to Informed Consent Form (ICF) signature or incomplete wound healing after surgery.
• Vaccination with a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention.

Más betegség

• History of allergy to immunoglobulins or MMAE.
• History of major ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsades de Pointes [TdP]).

Laborértékek

• 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.

Egyéb

• Peripheral sensory neuropathy Grade >= 2.
• Pregnancy or lactation.
• Unable or unwilling to sign the ICF, or patient is incarcerated.

• Age 18 years or older.
• Histologically and radiologically confirmed advanced surgically unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) or other solid tumors.
• 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.
• 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.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Estimated life expectancy >= 3 months per investigator's assessment.
• 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.
• Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram, and Fridericia-corrected QT interval (QTcF) < 470 ms for both sexes.
• Availability of archival or fresh tumor tissue for biomarker analysis.