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

• Status: Active, not recruiting
• Trial end date: 2022-01-04
• Target enrollment: 0
• Participant gender: All

Summary

Study design This is a Phase II, open-label, multi-drug, multi-center, multi-arm, signal-searching study in patients with extensive-stage small-cell lung cancer (SCLC) who have refractory or resistant disease from prior platinum-based chemotherapy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Treatments: Adavosertib; Carboplatin; Durvalumab; Olaparib; Tremelimumab

Criteria

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