Non-small cell lung cancer (NSCLC)
Conditions
Interventions
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Written informed consent; - Histologically confirmed stage IIIB (without curative treatment options) and stage IV NSCLC. Tumor mutation status must be known, analyzed by next generation sequencing for specific mutations; - A tumour tissue sample (< 6 month old); - Any line of previous chemotherapy (but at least 1 line), with washout period of at least 4 weeks; - At least one unidimensionally measurable lesion according to RECIST1.1 criteria; - Age * 18 years; - ECOG / WHO performance status of 0 or 1; - Life expectancy of *12 weeks; - Body weight > 30 kg; - Adequate normal organ and bone marrow function: - Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. - Women 1 year ago, had chemotherapy-induced menopause with last menses >;1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). - Subject is willing and able to comply with the protocol for the duration of the study; - Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate. Female patients with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
Exclusion criteria
Exclusion criteria: - Involvement in the planning and/or conduct of the study - Participation in another clinical study with an investigational product during the last 3 months. - Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. - Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) 1 month prior to the first dose of study drug (wash out period). - Primary tumor smaller than 3 cm. - Any unresolved toxicity NCI CTCAE Grade * 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. - Patients with Grade * 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. - Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician. - Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. - Any history of radiotherapy treatment to the chest. - Any prior radiotherapy (including palliative radiotherapy to non-target lesions) within 4 month of the first dose of study drug. - Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. - History of leptomeningeal carcinomatosis - Subjects with untreated CNS metastases are excluded. - Active or prior documented autoimmune or inflammatory disorders - Uncontrolled intercurrent illness - Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period. - History of allogenic organ transplantation. - History of active primary immunodeficiency - Active infection including tuberculosis, hepatitis B, hepatitis C, or HIV. Patients with a past or resolved HBV infection and absence are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV RNA - Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab - Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP - Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. - Patients who have received any prior anti-PD-1, anti PD-L1 or anti CTLA-4. - Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. - Judgment by the investigator that the patient is unsuitable to participate in the study - Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Establishing MTD in 3 sequential combination immunotherapy * radiotherapy cohorts. Percentage of grade III/IV toxicities determined between first radiotherapy day and 8 weeks after combination treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| All AEs, PFS, OS, response rate, T cell immune response (intracellular production of IL-2, IFN-*, TNF-* and IL-4 by CD4+ en CD8+ T cells to 6 different stimuli). | — |
Countries
Netherlands
Outcome results
None listed