A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab Following Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Patients With Unresected Stage I/II, Lymph-node Negative Non-small Cell Lung Cancer (PACIFIC-4/RTOG-3515)

This is a Phase III, randomised, double-blind, placebo-controlled, multi-centre study assessing the efficacy and safety of durvalumab versus placebo following SBRT in patients with Stage I/II Non Small Cell Lung Cancer

Inclusion Criteria:
• Patients must have histologically or cytologically documented Stage I-II NSCLC (American Joint Committee on Cancer Stage [8th edition]), with medically inoperable T1-T3N0M0 disease. Patients with medically operable T1-T3N0M0 NSCLC who choose to have SBRT are also eligible.
• Patients with central or peripheral lesions are eligible. Central lesions are defined as tumor within or touching the zone of the proximal bronchial tree, defined as a volume of 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus right, and left lower lobe bronchi). Patients with Ultra central tumors are NOT eligible. Ultra‐central tumors are defined as tumors abutting the trachea, mainstem bronchus, or esophagus.
• Tumor sample requirements: provision of an archived tumor tissue block (or at least 15 newly cut unstained slides) ≤6 months old. If an archival sample is not available, provision of a recent (≤3 months) tumor biopsy is encouraged, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk. If tissue is not available, patients may still enrol on trial.
• Completion of SBRT as definitive treatment within 7 days of randomization
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2 at enrollment and randomization.
• No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 anti- (PD-L2) antibodies, excluding therapeuticanticancer vaccines.
• Adequate organ and marrow function as defined by the following criteria prior to randomization: Hgb >9.0g/dl; Absolute neutrophil count >1.0 x 109/L; Platelet count >75 x 109/L; Serum bilirubin <1.5x ULN;Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit normal;CrCl > 30 ml/min

Exclusion Criteria:
• Mixed SCLC and NSCLC histology
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
• Any unresolved toxicity CTCAE >Grade 2 from SBRT. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study drug may be included after consultation with the AstraZeneca/MedImmune medical monitor.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure (NYHA Class III or IV ), uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active 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
• History of non-infectious pneumonitis requiring steroids, or patients with Grade ≥2 pneumonitis
Phase III
Rachel Sanborn, M.D.
Brenda Fisher
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Franz Clinic
  • Providence Portland Medical Center