A Phase II, Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients with Platinum Refractory Extensive-Stage Small-Cell Lung Cancer

Exclusion Criteria

• (applicable to all arms):
• • Participation in another clinical study, major surgery, radiation therapy within 28 days.
• • Any condition that, in the opinion of the Investigator, would interfere with the evaluation of the IP or interpretation of patient safety or study results.
• • Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.
• • History of another primary malignancy, leptomeningeal carcinomatosis or spinal cord compression.
• Exclusion criteria (Arm A specific)
• • Active autoimmune disease, including a paraneoplastic syndrome.
• • Active or prior documented autoimmune or inflammatory disorders.
• • Any unresolved toxicity (CTCAE Grade >2) from previous anticancer therapy.
• • Active infection including tuberculosis, HIV, Hepatitis B or C.
• Exclusion criteria (Arm B specific)
• • Prior exposure to any WEE1 inhibitors.
• • Products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4. Co-administration of rosuvastatin, atorvastatin, simvastatin and lovastatin, aprepitant or fosaprepitant or any herbal preparations. Grapefruit and Seville oranges should be avoided while taking AZD1775.
• • Any known hypersensitivity or contraindication to IP or CBDP.
• • QTcF > 470 msec or congenital long QT syndrome.
• • Any current or within 6 months cardiac diseases NYHA ≥ Class 2: unstable angina pectoris, congestive heart failure, acute MI, conduction abnormality not controlled with pacemaker or medication, significant ventricular or supraventricular arrhythmias.
• • A recent history of Torsades de pointes.
• Exclusion criteria (Arm C specific)
• • Cytotoxic chemotherapy within 21 days of Cycle 1 Day 1 is not permitted
• • Previous treatment with a PARP inhibitor (including olaparib) or ATR inhibitor
• • Concomitant use of known strong CYP3A inhibitors and moderate CYP3A inhibitors
• • Concomitant use of known strong and moderate CYP3A inducers
• • Persisting (> 4 weeks) severe pancytopenia due to previous therapy
• • Cardiac dysfunction
• • Refractory nausea and vomitting, chronic gastrointenstinal diseases or previous significant bowel resection
• • Patients with uncontrolled seizures
• • Intenstinal obstruction or CTCAE grade 3 or grade 4 GI bleeding within 4 weeks before dosing