This is an open-label, single arm, phase 2 trial enrolling patients with untreated Extensive-Stage Small-Cell Lung Cancer (ES SCLC), with a strong translational attitude.
The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
Male/female participants who are at least 18 years of age on the day of signing informed consent.
Cytologically/histologically confirmed diagnosis of SCLC per the Veterans Administration Lung Study Group (VALG) staging system will be enrolled in this study. Patients must have extensive stage (ES) SCLC defined as Stage IV (T any, N any, M 1a/b/c) by the American Joint Committee on Cancer, Eighth Edition.
Possibility of obtaining tissue sample, via a biopsy of the primary tumour or metastatic tumour tissue, within the 6 weeks prior to study entry. An archival biopsy is acceptable as long as there has been no intervening anticancer treatment since the time the biopsy was obtained to enrolment in this clinical study and as long as it was within 6 weeks of study entry. Tissue sample would consist of formalin-fixed, paraffin-embedded tumour tissue blocks, or, from formalin-fixed paraffin-embedded tumor tissue block, at least five re-cut, unstained sections of 5 μM thickness for immunohistochemical analysis and five unstained sections of 10 μM thickness for NGS, presented on slides or cell-block.
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
Rash must cover less than 10% of body surface area;
Single group
Pembrolizumab/Olaparib
DrugPatients will receive pembrolizumab 200 mg 1q21 and chemotherapy -platinum compound (cisplatin 75 mg/m2 or carboplatin area under the curve of 5 mg per milliliter per minute) 1q21 plus etoposide 100 mg/m2 1-3q21- for 4 cycles (Induction Phase). In case of responsive or stable disease, patients will receive pembrolizumab 200 mg 1q21 plus olaparib 300 mg twice daily until progression (Maintenance Phase) or up to a maximum of 35 cycles.
Progression free survival (PFS)
Time from registration to the first documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by local site or death due to any cause, whichever occurs first.
Objective response rate (ORR)
Percentage of patients who have a confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1) during the induction and the maintenance phases of treatment.
Immune-related Objective response rate (irORR).
Percentage of patients achieving a complete response (CR) or partial response (PR), according to immune-modified RECIST 1.1 criteria, during the induction and the maintenance phases of treatment.
Progression free survival (PFS) at 6, 12, and 24 months
Percentage of patients alive and progression-free at 6, 12, and 24 months.
Overall Survival (OS)
Time from registration to death due to any cause
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Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
