I. Determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of olaparib in combination with durvalumab and radiation therapy (RT).
I. To observe and record anti-tumor activity. II. Correlate response with the circulating frequency and diversity of T cells within the peripheral blood.
III. Evaluate the safety and toxicity of olaparib in combination with durvalumab and RT.
I. Evaluate the genetic and clinicopathologic markers of response and resistance including prior receipt of platinum therapy.
II. To correlate response with baseline tumoral immune infiltrate.
OUTLINE: This is a dose-escalation study of olaparib in combination with fixed dose durvalumab and radiation therapy.
Patients receive olaparib orally (PO) twice daily (BID) on days 1-28 and durvalumab intravenously (IV) over 55-65 minutes on day 1 of each cycle. Beginning cycle 2, patients also undergo radiation therapy daily on weekdays for 3 weeks. Chemotherapy and immunotherapy cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 90 days and every 12 weeks thereafter for two years on until death, whichever occurs first.
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