Response and Toxicity Prediction by Microbiome Analysis After (Concurrent) Chemoradiotherapy

Prior treatment

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Has had prior monoclonal antibody therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Previous treatment with PD-1-PD-L1 axis inhibiting immunotherapy.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Subjects who have undergone organ transplant or allogeneic stem cell transplantation.

Other illness

• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions:
  • Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
  • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
  • Skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic immunosuppressive treatment, in particular corticosteroids are permitted to enrol.
• Active malignancy or a prior malignancy within the past 3 years, with the following exceptions:
  • Patients with completely resected basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and patients with isolated elevation in prostate-specific antigen or low risk prostate cancer (managed with watchful waiting) are allowed.
  • Patients who underwent mediastinal radiotherapy in the past are not allowed.
• Subjects with chronic infections/infectious disorders (eg. Clostridium colitis)
• Has evidence of symptomatic interstitial lung disease or an active, non-infectious pneumonitis.
• Has an active chronic infection requiring systemic therapy.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Lab values

• Have known but untreated driver mutations of the EGFR gene or ALK or ROS1 translocation.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

• Stages IIIA, IIIB and IIIC (as per UICC 8th TNM edition) NSCLC (histologically or cytologically confirmed) amenable for durvalumab treatment after sequential or concurrent chemoradiotherapy according to local standards. Patients that received neoadjuvant/adjuvant chemotherapy for surgically treated stages I to III NSCLC are allowed as long as therapy was completed at least 6 months prior to the diagnosis of disease recurrence amenable for chemoradiotherapy and resolution of all treatment related toxicity ≤ grade 1 .
• No signs of disease progression after CCRT
• At least 1 cycle of chemotherapy before or concurrent during radiotherapy but no more chemotherapy between last radiotherapy session and start durvalumab
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Absence of any of following targetable driver mutations: EGFR, ALK, ROS1
• over 18 years
• ECOG 0-1
• Must be willing to provide collected stool samples and allow to obtain a throat swab during the observation period. A pulmonary protected brush swab will only be optionally performed in a selected number of patients.
• Demonstrate adequate organ function