Non-small cell lung cancer (NLCLC) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Imfinzi
Product Name: Imfinzi
Pharmaceutical Form: Infusion
INN or Proposed INN: DURVALUMAB
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Other descriptive name: IMFINZI
Concentr
Sponsors
Oslo University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study patients must fulfill all of the following criteria: 1. Locally-advanced, unresectable, stage 3 NSCLC (including PET-CT and MRI-brain in the diagnostic work-up). 2. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 3. Diagnostic biopsy with PDL1 30 kg 9. Adequate normal organ and marrow function as defined below: ? Hemoglobin =9.0 g/dL ? Absolute neutrophil count (ANC) 1.5 (or 1.0) x (> 1500 per mm3) ? Platelet count =100 (or 75) x 109/L (>75,000 per mm3) ? Serum bilirubin =1.5 x institutional upper limit of normal (ULN). ? AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN ? Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance 10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. 11. Women of childbearing potential should have a negative urine or serum pregnancy test within 7 days prior to receiccing first dose of study medication. if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A woman is considered WOCBP, i.e. fertile, following menarche and untill becoming post-menopausal unkess permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. 12. WOCBP should use an adequate method to avoid pregnancy 13.Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for a period of 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo five half-lives 14.Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Non-small cell lung cancer disease suitable for curative surgery 2. Significant cardiac, pulmonary or other medical illness that would limit activity or survival 3. 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 during the last 2 weeks. 4. Any concurrent chemotherapy, Investigational product (IP), biologic- or homonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (e.g. hormone replacement therapy) is acceptable. 5. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. 6. History of allogenic organ transplantation. 7. Active or prior documented autoimmune or inflammatory disorders The following are exceptions to this criterion: a. Patients with vitiligo or alopecia b. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement c. Any chronic skin condition that does not require systemic therapy d. Patients without active disease in the last 5 years may be included but only after consultation with the study physician e. Patients with celiac disease controlled by diet alone 8. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 9. History of another primary malignancy except for a. Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease c. Adequately treated carcinoma in situ without evidence of disease 10. History of active primary immunodeficiency or medical condition requiring high doses (>30 mg prednisolone daily) of systemic steroids or other forms of immunosuppressive therapy 11. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), and hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 12. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) b. Systemic corticosteroids at physiologic doses not to exceed > of prednisone or its equivalent c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 13. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Pa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if patients with a high tumour mutational burden, TMB (>8.5 mutations per megabase) have a hazard ratio equal to or less than 0.55 as compared to patients with low TMB.;Secondary Objective: 1. To investigate different levels of TMB in tumour tissue compared to blood samples, as predictors for development of clinical response 2. To characterise the transcriptome (RNA seq) 3. To investigate urine for predictive biomarkers (ctDNA, miRNA) 4. To evaluate if selected biomarkers correlate to progression-free survival and overall survival in PDL1 negative and positive patients receiving the PD-L1-inhibitor durvalumab after chemoradiation 5. To investigate the immunological response, tumour development (if present) and dynamics in the tumour micro-environment 6. To investigate if chemoradiation upregulates / changes PDL1 expression in the PDL1 negative / positive patients 7. To evaluate if biomarkers predict toxicity of this treatment in lung cancer patients ;Primary end point(s): Patients with high Tumour Mutational Burden, TMB (> 8.5 mutations per megabase) have a hazard ratio equal to or less than 0.55 as compared to patients with low TMB.;Timepoint(s) of evaluation of this end point: Evaluation is planned when all included patients are followed-up for two years after start of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Tumour Mutational Burden, TMB in tumor tissue and blood samples are associated and are predictive of clinical response 2. Specific RNA profiles predict response to treatment 3. Molecular profiles in urine predict response to treatment 4. Analysis of pre-treatment and under-treatment samples may identify biomarkers for predicting which patients will benefit from treatment with durvalumab after chemoratiation 5. The durvalumab treatment following chemoradiatio will induce T cell responses against antigens expressed in each patient´s tumor 6. A possible change in PDL1 status will be explored 7. The durvalumab treatment following chemoradiation has acceptable safety and tolerability in NSCLC patients, as assessed by Patient Reported Outcome measurements.;Timepoint(s) of evaluation of this end point: Evaluation is planned when all included patients are followed-up for two years after start of treatment. | — |
Countries
Finland, Lithuania, Norway
Contacts
Public ContactNational Coordinating Investigator
Oslo University Hospital
Outcome results
None listed