Limited-Stage Small Cell Lung Cancer (LS-SCLC) MedDRA version: 21.1 Level: LLT Classification code 10041071 Term: Small cell lung cancer stage unspecified System Organ Class: 100000004864
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Has pathologically (histologically or cytologically) confirmed SCLC. 2.Has LS-SCLC (Stage I-III, by AJCC 8th Edition Cancer Staging), and can be safely treated with definitive radiation doses. 3.Has no evidence of metastatic disease by whole body PET/CT scan, CT or MRI scans of diagnostic quality of chest, abdomen, pelvis and brain. The process for image collection and transmission to the central imaging vendor can be found in the Site Imaging Manual. 4.Has at least 1 lesion that meets the criteria for being measurable, as defined by RECIST 1.1, and is appropriate for selection as a target lesion, as determined by local site investigator/radiology review. 5.Has not received prior treatment (chemotherapy or radiotherapy or surgery resection) of LS-SCLC. 6.Is not expected to require tumor resection during the course of the study. 7.Must submit a pre-treatment tumor tissue sample. Any available tumor tissue sample can be submitted: histologic (ie, core, incisional, or excisional biopsy) or cytologic sample (if tissue sample unavailable). The sample should be submitted before or within 4 weeks after randomization; however, participants may be enrolled into the study before the pre-treatment tissue sample is submitted. 8.Has ECOG Performance score 0 or 1 assessed within 7 days prior to the first administration of study intervention. 9.Has a life expectancy of at least 6 months. 10.Has adequate PFT defined as an FEV1 >50% of predicted normal volume and a DLCO >40% of predicted normal value. Participants for whom DLCO measurements are not available will be deemed to have adequate oxygen transfer if pulse oximetry (O2 saturation) =90% room air. 11.Has adequate organ function; all screening laboratory tests should be performed within 10 days prior to initiation of study intervention. 12.Male participants are eligible to participate if they agree to the following during the intervention period and for at least 180 days after the last dose of study intervention: -Refrain from donating sperm PLUS either: -Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR -Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below: Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 13.A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: -Is not a WOCBP OR -Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. -A W
Exclusion criteria
Exclusion criteria: 1.Has extensive stage disease, defined as stage IV (T any, N any M1a/b), or T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. 2.Has history, current diagnosis, or features suggestive of MDS/AML. 3.Has had documented weight loss >10% (from baseline) in the preceding 3 months. 4.Has a radiation treatment plan that is likely to encompass a volume of whole lung (total lung V20-GTV) receiving >20 Gy in total (V20) of more than 35% of lung volume. 5.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor. 6.Has received prior therapy with olaparib or with any other PARP inhibitor. 7.Had major surgery 500 ms, electrolyte disturbances, etc.), or participants with congenital long QT syndrome. 15.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention. 16.Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. 17.Has severe hypersensitivity (= Grade 3) to study intervention and/or any of its excipients. 18.Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 19.Has a known history of, or active, neurologic paraneoplastic syndrome. 20.Has a history of (non-infectious) pneumonitis/interstitial lung disease that requires steroids or has current pneumonitis/interstitial lung disease. Lymphangitic spread of the LS-SCLC is not exclusionary. 21.Has an active infection requiring systemic therapy. 22.Has a known history of human immunodeficiency virus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare progression free survival (PFS) per RECIST 1.1 as assessed by BICR 2. To compare overall survival (OS) ;Secondary Objective: 1.To evaluate the safety and tolerability (ST) of concurrent chemoradiation therapy with pembrolizumab followed by pembrolizumab plus olaparib (Group B) compared to concurrent chemoradiation therapy alone (Group C) 2.To evaluate ST of concurrent chemoradiation therapy with pembrolizumab followed by pembrolizumab (Group A) compared to Group C 3.To compare Group B to Group C with respect to objective response rate (ORR) as assessed by BICR per RECIST 1.1 4.To compare Group A to Group C with respect to ORR as assessed by BICR per RECIST 1.1 5.To compare Group B to Group C with respect to duration of response (DOR) as assessed by BICR per RECIST 1.1 6.To compare Group A to Group C with respect to DOR as assessed by BICR per RECIST 1.1 7.To evaluate change from baseline (CFB) (at Cycle 1) and time to true deterioration (TTD) in global health status/quality of life (QoL) in Group B compared to Group C 8.To evaluate CFB (at Cycle 1) and the TTD in QoL in Group A compared to Group C;Primary end point(s): 1. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1): the time from randomization to progression or death due to any cause, whichever occurs first 2. Overall Survival (OS): the time from randomization to death due to any cause;Timepoint(s) of evaluation of this end point: 1. Up to approximately 59 months 2. Up to approximately 82 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Number of Participants Experiencing an Adverse Events (AEs) 2. Number of Participants Discontinuing Study Treatment Due to Adverse Events (AEs) 3. Objective Response (OR): complete response (CR) or partial response (PR) 4. Duration of Response (DOR): the time from the earliest date of first documented evidence of confirmed CR or PR until the earliest date of disease progression or death from any cause, whichever comes first 5. Change from Baseline at Cycle 1 in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 & 30) Scale Score 6. Change from Baseline at Cycle 1 in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score 7. Change from Baseline at Cycle 1 in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score 8. Change from Baseline at Cycle 1 in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score 9. Change from Baseline at Cycle 1 in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score 10. Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score 11. Time to True Deterioration (TTD) in Cough (LC13/Item 1) Scale Score 12. Time to True Deterioration (TTD) in Chest Pain (LC13/Item 10) Scale Score 13. Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score 14. Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score;Timepoint(s) of evaluation of this end point: 1. Up to approximately 82 months 2. Up to approximately 82 months 3. Up to approximately 82 months 4. Up to approximately 82 months 5. Baseline and Week 24 6. Baseline and Week 24 7. Baseline and Week 24 8. Baseline and Week 24 9. Baseline and Week 24 10. Up to 78 weeks 11. Up to 78 weeks 12. Up to 78 weeks 13. Up to 78 weeks 14. Up to 78 weeks | — |
Countries
Australia, Belgium, Bulgaria, Canada, China, Estonia, France, Greece, Hungary, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Portugal, Romania, Russian Federation, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed