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

Inclusion criteria (applicable to all arms)

* Adults with histologically or cytologically documented ED SCLC who have demonstrated progressive disease either during first-line platinum-based chemotherapy (platinum refractory) or within 90 days of completing platinum based-chemotherapy (platinum resistant) and have not received further treatment.
* Brain metastases must be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment.
* At least 1 lesion, not previously irradiated, that can be accurately measured at baseline (per RECIST v 1.1 guidelines)
* Life expectancy of at least 8 weeks.
* WHO/ ECOG PS of 0-1 at enrollment.

Inclusion criteria (Arm A specific)

* Body weight \>30 kg.
* No prior exposure to immune mediated therapy, excluding therapeutic anticancer vaccines.

Inclusion criteria (Arm B specific) • Able and willing to swallow oral medication.

Inclusion criteria (Arm C specific)

• Able and willing to swallow oral medication.

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