AZD1775 Combined With Olaparib in Patients With Refractory Solid Tumors

This is a Phase Ib, multi-centre study of AZD1775 combined with olaparib administered orally in patients with refractory solid tumours, or as combination therapy for relapsed small-cell lung cancer (SCLC). There are 2 parts to the study: Part A: Dose Escalation Part B: Dose Expansion In Part A, patients with refractory solid tumours will be assessed for safety, tolerability, and pharmacokinetics (PK) of AZD 1775 when combined with olaparib. Different dose levels will be administered to identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D). The dose expansion part (Part B) will further explore the safety, PK, and preliminary efficacy of the AZD1775 RP2D and dosing schedule for the treatment of patients with SCLC who previously had a confirmed response (either a Complete Response or Partial Response) to first-line platinum therapy and then relapsed. Patients who progressed whilst on platinum-containing therapy (platinum refractory) are not permitted to enter the study.. An olaparib pharmacokinetic (PK) sub-study will precede the combined treatment with AZD1775 and olaparib for all patients in Part A. In the sub-study single agent olaparib will be given orally BID for 3 or 5 consecutive days and venous blood samples will be collected on Day 3 or Day 5 as appropriate for assessment of the multiple dose pharmacokinetics of single agent olaparib. Patients will experience a short gap in treatment (approximately 4-5 days) between Day 3 or Day 5 of the olaparib PK sub-study and Cycle 1 Day 1 of the combination treatment. Patients will continue to receive treatment with AZD1775 and Olaparib until disease progression, intolerable toxicity, or discontinuation criteria have been met.