Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Neoplasm, Residual

Adenocarcinoma of Lung

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Durvalumab

Antineoplastic Agents, Immunological

All subjects will receive four cycles of durvalumab with SABR concurrent at cycle 2, then will be evaluated for MRD. Subjects in this arm have no detectable ctDNA at MRD landmark and will receive no further therapy.

All subjects will receive four cycles of durvalumab with SABR concurrent at cycle 2, then will be evaluated for MRD. Subjects in this arm have detectable ctDNA at MRD landmark and are randomized to no further therapy.

All subjects will receive four cycles of durvalumab with SABR concurrent at cycle 2, then will be evaluated for MRD. Subjects in this arm have detectable ctDNA at MRD landmark and are randomized to eight additional cycles of durvalumab

Subjects will receive durvalumab 1500mg IV every four weeks for four cycles, undergo assessment for residual disease, then a subset of subjects will receive an additional eight cycles of durvalumab.

Subjects will receive stereotactic radiation therapy concurrent with cycle 2 of durvalumab to a dose of 48Gy in four fractions. Fractionation may be modified for central tumors.

Stereotactic Body Radiotherapy

After four cycles of durvalumab, subjects will be evaluated at the MRD Landmark for residual ctDNA to determine subsequent treatment assignment.

Circulating Tumor DNA assay

Layla Mahmud

Islam Mohamed, MD

Sanjay Rao, MD

Devin Schellenberg, MD

Angela Chan, MD

Shilo Lefresne, MD

Barb Melosky, MD

Julianna Caon, MD

Zia Poonja, MD

Anand Swaminath, MD

Peter Ellis, MD

The SCION Trial is a clinical trial in patients with early stage non-small cell lung cancer. The purpose of the trial is to investigate whether it is safe and effective to combine standard radiation treatment with a drug called durvalumab, a type of immunotherapy. In addition, the study will use a blood test to look for cancer cell DNA to determine how long treatment with durvalumab should last. Both the use of durvalumab and the use of the blood test are new strategies for managing early stage non-small cell lung cancer.

PURPOSE The intent of the study is to determine whether disease control in early non-small cell lung cancer (NSCLC) achieved by stereotactic ablative body radiotherapy (SABR) can be augmented locally, regionally, and distantly by safely combining it with durvalumab. Moreover, the study will assess whether patients who are likeliest to benefit from extended treatment with durvalumab can be predicted by assaying for molecular residual disease (MRD) after initial treatment using the AVENIO assay for circulating tumor DNA (ctDNA).

HYPOTHESIS Combining SABR and Durvalumab in patients with T1-2 N0 M0 NSCLC reduces the overall relapse rate at 18 months by 50% compared with historical controls treated with SABR alone, from 19.3% to 9.7%.

OBJECTIVES Primary

• To determine the overall relapse rate at 18 months in patients with T1-2 N0 M0 NSCLC treated with SABR and Durvalumab.

Secondary

* To determine rates of Local Relapse, Regional Nodal Relapse, Distant Relapse, and Second Primary Lung Cancer in patients with T1-2 N0 M0 NSCLC treated with SABR and Durvalumab.
* To determine rates of Overall Survival, Cause-Specific Survival, and Relapse Free Survival in patients with T1-2 N0 M0 NSCLC treated with SABR and Durvalumab
* To determine rates of pneumonitis, immune-related toxicity, adverse events, serious adverse events in patients with T1-2 N0 M0 NSCLC treated with SABR and Durvalumab.
* To determine the rate of MRD detection using the AVENIO ctDNA assay in patients with T1-2 N0 M0 NSCLC treated with SABR and Durvalumab.
* To compare clinical outcomes between patients with detectable versus undetectable MRD using the AVENIO ctDNA assay following treatment with SABR and Durvalumab.
* To compare clinical outcomes between patients with detectable MRD using the AVENIO ctDNA assay following treatment with SABR and Durvalumab who receive extended Durvalumab versus no further therapy.

STUDY DESIGN Subjects who meet the eligibility criteria will be candidates for enrolment. All subjects will receive one infusion of Durvalumab every 4 weeks for four cycles (4 weeks = 1 cycle), with SABR delivered concurrently with cycle 2. Subjects will be assessed at baseline using the AVENIO assay initially on tumor tissue. This will allow the subsequent evaluation for molecular residual disease (MRD) following cycle 4 to be tumor-informed, and ultrasensitive. Subjects with no detectable ctDNA at the MRD assessment will receive no further therapy. Subjects with detectable ctDNA at the MRD assessment will be randomized to receive either no further therapy or 8 additional cycles of q4w Durvalumab. Safety will be evaluated by recording the occurrence of adverse events, serious adverse events, and laboratory abnormalities, with special attention to pneumonitis and immune-related toxicity.

Future research will be enabled through the collection of biospecimens. Subjects will separately consent to the optional collection of these biospecimens. Blood samples collected for this purpose at multiple timepoints (0, 4, 12, 24 months) will be archived in a biorepository created for this study operated by the BC Cancer Tumour Tissue Repository (Victoria, BC). Stool samples collected for this purpose at multiple timepoints (0, 4, and 12 months) will be archived in the Oncomicrobiome Repository (Montreal, QC).

Study subjects will be analyzed as a single cohort with respect to the primary outcome, with comparison to historical controls. Treatment assignment based on biomarker status after initial treatment.

SCION: SABR and Checkpoint Inhibition Of NSCLC

A Phase II Study of Circulating Tumor DNA Directed Consolidation Durvalumab (MEDI4736) Following Induction and Concurrent Durvalumab With SABR for Stage I NSCLC. SCION: SABR and Checkpoint Inhibition Of NSCLC

Fraction of subjects experiencing relapse at 18 months following initial therapy

Evaluation of radiographic response by CT and PET/CT

Recurrence at irradiated primary tumor site

Recurrence in a hilar or mediastinal node

Proportion of subjects surviving lung cancer in the absence of other causes of death

Proportion of subjects surviving without relapse

Proportion of subjects diagnosed with a second primary lung cancer at a site beyond the treatment volume

Proportion of subjects with detectable ctDNA on MRD Landmark assay

Number and severity of serious adverse events

Number and severity of subjects experiencing pneumonitis

Number and severity of subjects experiencing immune-related adverse events

Spots Global Cancer Trial Database for lung squamous cell carcinoma stage i