MT-601 Administered To Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer

A Phase 1 Study With Expansion of Patient-Derived Multi-Tumor-Associated Antigen Specific T Cells (MT-601) Administered To Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer (PANACEA)

The goal of this clinical trial is to assess safety and tolerability of escalating doses of MT-601 administered during the off week of chemotherapy regimen for patients with pancreatic cancer. The main question[s] it aims to answer are: safety and efficacy • overall response rate and duration of response. Participants will meet all applicable inclusion criteria prior to chemotherapy and must agree to provide apheresis material.

The Dose Escalation portion of the study will use a modified 3+3 design to define an acceptable dose of MT-601 in combination with maintenance capecitabine following completion of FFX or NLX chemotherapy. For the Dose Expansion, MT-601 will be administered at the dose determined to be safe based on the results from the Dose Escalation portion. Front-line chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) will be administered as per standard of care. MT-601 will be administered intravenously over no less than 5 minutes as a single dose following completion of all planned doses of FFX or NLX chemotherapy and after participants have started receiving maintenance capecitabine.

Inclusion Criteria:

1. Informed Consent

2. Age ≥ 18 years

3. ECOG performance status of 0 to 1

4. Cytologically or histologically confirmed, locally advanced, unresectable or metastatic pancreatic adenocarcinoma (pancreatic carcinomas with at least some component of adenocarcinoma included).

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

6. Prior receipt of at least 4 doses (~2 months) of FFX or NLX with plans for completion of 12 doses (~6 months)

7. Absence of progression during treatment with FFX or NLX (eg. CR, PR, or SD at study entry)

8. Adequate pulmonary function with partial pressure of oxygen (pO2) on room air of at least 90%

9. Adequate cardiac function with an ejection fraction ≥ 45%

10. Adequate organ function, as defined below:

    • Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed)
    • Platelets ≥75,000/mm3 (supportive medications allowed)
    • Hemoglobin ≥9 gm/dL (transfusion allowed)
    • Total bilirubin ≤2.0 × ULN unless considered due to Gilbert's syndrome in which case, ≤ 3.0 x ULN
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × ULN OR ≤5 × ULN if known tumor involvement of liver
    • Serum creatinine ≤2 × ULN OR estimated glomerular filtration rate (using institutional standard) ≥50 mL/min

11. Willingness to use adequate contraception throughout study and for a period of 3 months after last dose of any study drugs

Exclusion Criteria:

1. Known CNS metastases or meningeal carcinomatosis unless treated and controlled for ≥ 3 months prior to the first administration of MT-601 without the need for increasing doses of steroids

2. Other known active cancer likely to require additional treatment in the next 2 years unless approved by Medical Monitor

3. Active bacterial, viral, or fungal infection requiring systemic therapy. Patients may be re-evaluated for eligibility upon completion of infection treatment.

4. Significant cardiovascular risk (eg, coronary stenting within 4 weeks, myocardial infarction within 6 months)

5. Diagnosis of significant immunodeficiency that in the Investigator or Medical Monitor's judgment would preclude participation in the study.

6. Administration of systemic steroid therapy (> 10 mg/day of prednisone equivalent) ≤ 7 days prior to the first administration of MT-601

7. Active autoimmune disease that required systemic treatment in the past 2 years (replacement therapies excluded [eg, thyroxine, insulin, physiologic corticosteroids])

8. History of solid organ or hematologic transplant

9. Known HIV

10. Evidence of active hepatitis B as defined by:

    1. Positive hepatitis B surface antigen (HBsAg), or
    2. Negative HBsAg but a positive hepatitis B surface antibody (HBsAb) or positive hepatitis B core antibody (HBcAb) with a positive hepatitis B virus (HBV) DNA

11. Evidence of active hepatitis C as defined by:

    a. Positive anti-hepatitis C virus antibody (HCVAb) with a positive hepatitis C virus (HCV) RNA by PCR

12. Pregnant or currently breast-feeding

13. Psychiatric illness/social situations that would interfere with compliance with study requirements