A Phase 1 Study of MC001 in Patients With Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) and Other Folate Receptor Alpha (FRα)-Expressing Solid Tumors

Medicovestor, Inc

Status and phase: Begins enrollment this month; Phase 1

Conditions: Advanced Solid Tumor Cancer; Metastatic Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma (PDAC); Metastatic Solid Tumors

Treatments: Biological: MC001

Study type: Interventional

Funder types: Industry

Identifiers

NCT07909356

MC001-101

Details and patient eligibility

About

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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 18 years or older.

2. Histologically and radiologically confirmed advanced surgically unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) or other solid tumors.

3. 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.

4. 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.

5. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

6. 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.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

8. Estimated life expectancy >= 3 months per investigator's assessment.

9. 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.

10. Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram, and Fridericia-corrected QT interval (QTcF) < 470 ms for both sexes.

11. Availability of archival or fresh tumor tissue for biomarker analysis.

Exclusion criteria

1. Prior exposure to antibody-drug conjugates (ADCs) targeting FRα or conjugated to monomethyl auristatin E (MMAE).

2. History of allergy to immunoglobulins or MMAE.

3. Receipt of radiation therapy <= 14 days before Cycle 1 Day 1, or failure to recover to Grade <= 1 from treatment-related side effects.

4. 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).

5. Peripheral sensory neuropathy Grade >= 2.

6. Active infection, including Human Immunodeficiency Virus (HIV), requiring systemic therapy within <= 7 days prior to Cycle 1 Day 1.

7. 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.

8. History of major ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsades de Pointes [TdP]).

9. Major surgical intervention <= 28 days prior to Informed Consent Form (ICF) signature or incomplete wound healing after surgery.

10. Vaccination with a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention.

11. Pregnancy or lactation.

12. Unable or unwilling to sign the ICF, or patient is incarcerated.

13. 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Part A: MC001 Dose Escalation (Phase 1a)

Experimental group

Description:

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.

Treatment:

Biological: MC001

Part B: MC001 Dose Expansion in PDAC (Phase 1b)

Experimental group

Description:

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.

Treatment:

Biological: MC001