Durvalumab vs Placebo With Stereotactic Body Radiation Therapy in Early Stage Unresected Non-small Cell Lung Cancer (NSCLC) Patients / Osimertinib Following SBRT in Patients With Early Stage Unresected NSCLC Harboring an EGFR Mutation

About

Brief Summary

This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab with SoC SBRT versus placebo with SoC SBRT in patients with unresected clinical Stage I/II lymph node-negative (T1 to T3N0M0) NSCLC.

An additional cohort will assess Osimertinib following SBRT in patients with early stage unresected T1 to T3N0M0 NSCLC harbouring an EGFR mutation.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 3

Eligibility

Gender

All

Healthy Volunteers

Minimum Age

18 Years

Maximum Age

130 Years

Main Cohort Key Inclusion Criteria:

Age ≥18 years
Planned SoC SBRT as definitive treatment
WHO/ECOG PS of 0, 1 or 2
Life expectancy of at least 12 weeks
Body weight >30 kg
Submission of tumor tissue sample if available
Adequate organ and marrow function required
Patients with central or peripheral lesions are eligible
Staging studies must be done during screening (PET-CT within 10 weeks)
Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions

Main Cohort Key Exclusion Criteria:

Mixed small cell and non-small cell cancer
History of allogeneic organ transplantation
History of another primary malignancy with exceptions
History of active primary immunodeficiency
Epidermal growth factor receptor local testing is strongly recommended prior to enrollment. Patients with a tumor harboring an EGFRm per local testing will be excluded from the main cohort
Prior exposure to immune-mediated therapy with exceptions

Osimertinib Cohort Key Inclusion Criteria

Age ≥18 years
Planned SoC SBRT as definitive treatment
World Health Organization (WHO)/ECOG PS of 0, 1, or 2
Patients with central or peripheral lesions are eligible
Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
Staging studies must be done during screening (PET-CT within 10 weeks)
Submission of available tumor tissue sample
Confirmation by local laboratory that the tumor harbors one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R)
Adequate bone marrow reserve or organ function required
Female patients should be using highly effective contraceptive measures
Male patients should be asked to use barrier contraceptives (ie, condoms) during sex with all partners during the trial and avoid procreation

Osimertinib Cohort Key Exclusion Criteria

Mixed small cell and non-small cell cancer
Patients currently receiving potent inducers of CYP3A4
Patients with known or increased risk factor for QTc prolongation
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
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

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