COMBINATORY IMMUNOTHERAPY-2 (COM-IT-2) A phase 2 randomised open two-arm study to assess the tolerability and efficacy of immunotherapy combined with extensive radiotherapyfor the treatment of stage IV non-small cell lung cancer

Prior treatment

• Previous treatment with PD1/PDL-1 inhibitor
• Radiotherapy given within the last 4 weeks prior to inclusion
• Known larger active brain metastases that cannot be treated with stereotactic radiotherapy. Patients with stable/previously treated brain metastases can be included. Patients with several smaller brain metastases may be included if the larger metastases are treated with stereotactic radiotherapy

Other illness

• Significant cardiac, pulmonary or other medical illness that would limit activity or survival
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Patients who test positive for hepatitis B, C or HIV
• Diagnosis of immunodeficiency or medical condition requiring high doses (>20 mg prednisolone daily) of systemic steroids or other forms of immunosuppressive therapy

Lab values

• Indication for radiotherapy other than stereotactic radiosurgery of brain metastases
  • Women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-drug-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 2 weeks prior to initiation of study drug. Positive test is exclusion criterion.
  • Known hypersensitivity to the immunotherapy regimen planned for the patient the investigational product
  • Live vaccine administered last 30 days, active infection requiring IV antibiotics, active viral hepatitis or HIV
  • Previous allogenic or organ transplant
  • Any reason why, in the opinion of the investigator, the patient should not participate
  • Pregnancy or lactation
  • Treatment with any investigational medicinal product (IMP) that may interfere with the study treatment, within 2 weeks prior to first administration of study drug.
  • Disease suitable for curative salvage surgery
• Patients with EGFR-mutation or ALK-translocation not previously treated with tyrosine kinase inhibitor

• Stage IV NSCLC with clinical indication of starting systemic treatment with immunotherapy alone or in combination with chemotherapy (first or later lines)
  • Women of childbearing potential (WOCBP) should use a highly effective method during the treatment period and for at least 5 months after the last dose of immunotherapy to avoid pregnancy. Methods considered as highly effective birth control methods include combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravaginal, injectable, implantable or transdermal), intrauterine device (including hormone-releasing), male condom, bilateral tubal occlusion, vasectomised partner or sexual abstinence
  • Able to understand oral and written information and able to answer questionnaires
• Available core or excisional biopsy of a tumour lesion
• Measurable disease according to RECIST criteria (RECIST 1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Life expectancy > 3 months
• At least 1 tumour lesion suitable for radiotherapy treatment
  • Age >18 years
  • Written informed consent
  • Adequate organ function based on clinical examination and lab values (o Hb>9 g/dL o Neutrophils >1500 pr mm3 o Estimated creatinine clearance >40 mL/min o AST and ALT <2.5 x upper normal limit (if liver metastases: AST/ALT must be <5x upper normal limit) o Serum bilirubin < 1.5 x upper normal limit)