Patients with unresected Stage I/II, lymph-node negative Non-small Cell Lung Cancer MedDRA version: 21.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Applicable to both cohorts: 1. Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling and analyses 2. Age =18 years 3. Histologically or cytologically documented Stage I to II NSCLC, with clinical T1 to T3N0M0 Stage I/II disease and planned to receive definitive treatment with SBRT (Stereotactic Body Radiation Therapy). Patients may be medically inoperable or are medically operable and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as definitive therapy 4. Planned SoC SBRT as definitive treatment 5. World Health Organization (WHO)/ECOG PS of 0, 1, or 2 6. Patients with central or peripheral lesions are eligible 7. Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions 8. Staging studies must be done during screening (PET-CT within 10 weeks) 9. Submission of available tumor tissue or cell block samples from FNA Main cohort (durvalumab) specific: 1. Life expectancy of at least 12 weeks 2. Body weight >30 kg 3. Adequate organ and marrow function required 4. Pulmonary Function Testing within 16 weeks of randomization Osimertinib cohort specific: 1. Confirmation by local laboratory that the tumor harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R) 2. Adequate bone marrow reserve or organ function required 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 633
Exclusion criteria
Exclusion criteria: Applicable to both cohorts: 1. Mixed small cell and non-small cell cancer 2. History of another primary malignancy with exceptions Main cohort specific: 1. Patients with a tumor harboring an EGFRm per local testing will be excluded from the main cohort 2. History of allogeneic organ transplantation 3. History of active primary immunodeficiency or autoimmune disorders 4. History of non-infectious pneumonitis requiring steroids 5. Active infection including tuberculosis, hepatitis B virus, hepatitis C virus, or human immunodeficiency virus 6. Prior exposure to immune-mediate therapy Osimertinib cohort specific: 1. Patients currently receiving potent inducers of CYP3A4 2. Patients with known or increased risk factor for QTc prolongation 3. Treatment with any of the following: -Preoperative or adjuvant platinum-based or other chemotherapy for the disease under investigation -Prior treatment with neoadjuvant or adjuvant EGFR TKI -Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 -Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib 4. Any of the following cardiac criteria -Mean resting corrected QT interval >470 msec, obtained from 3 ECGs -Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG. -Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained -sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval -Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Applicable to main cohort: To assess the efficacy of durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of PFS in patients with subset of T1T1 to T3N0M0 NSCLC Applicable to osimertinib cohort: To assess the efficacy of osimertinib following SoC SBRT in patients with T1 to T3N0M0 in terms of 4-year PFS;Secondary Objective: Applicable to main cohort: To assess the efficacy of durvalumab with SBRT (Stereotactic Body Radiation Therapy) compared to placebo with SBRT in terms of: - PFS in patients with T1 to T3N0M0 NSCLC - Overall Survival - PFS24, TTP, TTDM, and PFS2 To assess the PK of durvalumab To investigate the immunogenicity of durvalumab To assess symptoms and health-related quality of life in patients treated with durvalumab with SBRT compared to placebo with SBRT using the EORTC QLQ-C30 To assess the safety and tolerability profile of durvalumab with SoC SBRT compared to placebo with SoC SBRT Applicable to osi cohort: -PFS by ICR according to RECIST 1.1 -OS, TTP, Time to CNS progression, PFS2 To assess the safety, tolerability, and compliance of a maximum of 3 years of osimertinib following SoC SBRT;Primary end point(s): Applicable to main cohort: PFS in patients with subset of T1 to T3N0M0 by BICR Applicable to osimertinib cohort: 4-years PFS by ICR using RECIST 1.1;Timepoint(s) of evaluation of this end point: On-study tumor assessments occur 8 weeks after randomization (after start of SBRT for osimertinib cohort), then every 12 weeks through week 116, then every 16 weeks through 3 years after randomization (after start of SBRT for osimertinib cohort), then every 6 months thereafter until objective disease progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Applicable to main cohort: PFS in patients with T1 to T3N0M0 NSCLC Overall Survival PFS24, TTP, and TTDM using BICR assessments according to RECIST 1.1 PFS2 using local assessment PK of durvalumab in serum Presence of ADA for durvalumab EORTC QLQ-C30: Change in symptoms, functioning, and global health status/quality of life Safety and tolerability: AEs, physical examinations, vital signs, electrocardiograms, and laboratory findings Applicable to osimertinib cohort: AEs (graded by CTCAE version 5) Laboratory studies: chemistry, hematology, and urinalysis Clinical evaluations ECG parametres LVEF WHO performance status PFS using RECIST 1.1 OS Site(s) of disease progression Time to CNS progression TTP PFS2;Timepoint(s) of evaluation of this end point: Both cohorts: OS: date of death Lung cancer mortality: date of death due to lung cancer TTP: date of progression (excluding deaths) PFS2: the earliest of progression event subsequent to first subsequent therapy or death Main cohort: PFS24: 24 months TTDM: date of death or distant metastasis Safety and tolerability: from randomization until 3 months after treatment discontinuation Osimertinib Cohort: Time to CNS progression: date of progression | — |
Countries
Belgium, Canada, China, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Türkiye, United Kingdom, United States
Contacts
Public ContactStudy Information Center
AstraZeneca AB
Outcome results
None listed