Safety and efficacy of adding immunotherapy combined with stereotactic radiotherapy in patients with limited metastatic pancreatic cancer (MEPANC-1)

Prior treatment

• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the planned first dose of the study. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
• Live virus vaccine within 30 days of planned start of trial treatment.
• Allergic reaction to M. obuense or had previously received IMM-101.
• Liver function insufficient to tolerate the prescribed dose of radiotherapy. To be determined by the treating radiologist.
• Lung function insufficient to tolerate the prescribed dose of radiotherapy. To be determined by the treating radiologist.
• Current or previous treatment with immunotherapeutic drugs.
• Second primary malignancy except in situ carcinoma of the cervix, adequately treated non-melanoma skin cancer, or other malignancy treated at least 3 years previously to diagnosis of pancreatic cancer and without evidence of recurrence.

Other illness

• An active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or other immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• History of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).
• Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
• Malignant ascites.

Other

• Metastasis in other organs than the lung and liver.
• Pregnancy, breast feeding.
• Positive PCR test for presence of SARS-CoV-2 during screening stage.
• Use of herbal remedies, including traditional Chinese herbal products (e.g., mistletoe).
• Otherwise deemed unsuitable by the Investigator.
• Histopathologically proven extra regional lymph node metastasis.
• Child-Pugh Classification grade B/C.
• Diffuse liver metastasis pattern on CT scan.

• Histologically confirmed (metastatic) pancreatic cancer, as indicated by a definite cytology/histology report.
• Adequate liver tests (bilirubin < 1.5 times normal; ALAT/ASAT < 5 times normal).
• Adequate bone marrow function (WBC > 3.0 x 109/L, platelets > 100 x 109/L and hemoglobin > 5.6 mmol/l).
• Effective contraceptive methods.
• Written informed consent.
• Patients who did not complete at least 8 cycles of FOLFIRINOX due to severe toxicity, will be included in the expansion cohort.
• ≤5 hepatic and/or pulmonary metastases in total.
• The combined diameter of all liver metastases AND the primary tumour or local recurrence in the pancreas is <9 cm.
• The combined diameter of all pulmonary metastases is <9 cm.
• CA 19-9 < 1000 IU/mL after completion of chemotherapy.
• Age > 18 years and < 75 years.
• WHO performance status of 0-2.
• Tumour volume of the primary tumour <7cmx7cmx7cm. Each diameter must not exceed 7 cm.
• Adequate renal function (eGFR ≥ 30 ml/min).