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

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.

Biological: MC001. 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.

Part A: MC001 Dose Escalation (Phase 1a) (experimental): 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.

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

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs). 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. Time frame: From first dose of study drug through 30 days after the last dose (up to approximately 36 months).

Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) in Part A (Dose Escalation). 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). Time frame: Cycle 1 (Day 1 to Day 21).

Maximum Observed Plasma Concentration (Cmax) of MC001 (ADC), Total Antibody, and Unconjugated MMAE. Time frame: Cycle 1 (Days 1, 2, 8, and 15) and Day 1 of subsequent 21-day cycles (up to approximately 36 months).

Area Under the Plasma Concentration-Time Curve (AUC) of MC001 (ADC), Total Antibody, and Unconjugated MMAE. Time frame: Cycle 1 (Days 1, 2, 8, and 15) and Day 1 of subsequent 21-day cycles (up to approximately 36 months).

Terminal Elimination Half-Life (T1/2) of MC001 (ADC), Total Antibody, and Unconjugated MMAE. Time frame: Cycle 1 (Day 1 through Day 15).

Objective Response Rate (ORR). Time frame: 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).

Duration of Response (DoR). Time frame: From date of first documented CR or PR until disease progression or death (up to approximately 36 months).

Disease Control Rate (DCR). Time frame: From first dose of study drug until disease progression or treatment discontinuation (up to approximately 36 months).

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 …

Enrollment: 40 participants (estimated).