A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Pembrolizumab (MK-3475) in Combination with Concurrent Chemoradiation Therapy Followed by Pembrolizumab with or without Olaparib (MK-7339), Compared to Concurrent Chemoradiation Therapy Alone in Participants with Newly Diagnosed Treatment-Naive Limited-Stage Small Cell Lung Cancer (LS-SCLC)
Placebo-controlled, Phase 3 study of concurrent chemoradiation therapy with pembrolizumab followed by pembrolizumab and olaparib in LS-SCLC (7339-013)
1. Has pathologically (histologically or cytologically) confirmed Small Cell Lung Cancer (SCLC).
2. Has Limited-Stage 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 positron emission tomography /computed tomography (PET/CT scan), CT or magnetic resonance imaging (MRI) scans.
4. Has at least 1 lesion that meets the criteria for being measurable, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
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 (formalin-fixed, paraffin embedded blocks are preferred to slides) including cytologic sample, if tissue sample unavailable.
8. Has Eastern Cooperative Oncology Group (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 organ function.
11. Male and female participants who are not pregnant and of childbearing potential must follow contraceptive guidance during the treatment period and for 180 days afterwards.
12. Male participants must refrain from donating sperm during the treatment period and for 180 days afterwards.
1. Has history, current diagnosis, or features suggestive of myelodysplastic syndrome/ acute myeloid leukemia (MDS/AML).
2. Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
3. Has received prior therapy with olaparib or with any other polyadenosine 5'diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor.
4. Had major surgery <4 weeks prior to the first dose of study intervention (except for placement of vascular access).
5. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
6. 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.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
8. Has severe hypersensitivity (>= Grade 3) to study intervention and/or any of its excipients.
9. Has an active autoimmune disease that has required systemic treatment in past 2 years.
10. Has a history of (non-infectious) pneumonitis/interstitial lung disease that requires steroids.
11. Has an active infection requiring systemic therapy.
12. Has a known history of human immunodeficiency virus (HIV) infection or Hepatitis B or known active Hepatitis C virus infection.
18age old over
No limit
Both
Small Cell Lung Cancer
- Biological: Pembrolizumab
Pembrolizumab 200 mg intravenouse (IV) Q3W (cycle1 to 4), Pembrolizumab 400 mg IV Q6W (cycle 5 to 13)
- Drug: Pembrolizumab placebo (saline)
Pembrolizumab placebo (saline) IV Q3W (cycle1 to 4) and Pembrolizumab placebo (saline) IV Q6W (cycle 5 to 13)
- Drug: Olaparib matching placebo
Olaparib matching placebo BID, PO
- Drug: Etoposide
Etoposide 100 mg/m2 IV Q3W, Day 1-3 (cycle 1 to 4)
- Drug: Platinum, investigator's choice
Carboplatin titrated to an area under the plasma drug concentration time curve (AUC) of 5 mg/mL/min IV Q3W on Day 1 of each cycle (cycle 1 to 4) or Cisplatin 75 mg/m2 IV Q3W on Day 1 of each cycle (cycle 1 to 4)
- Radiation: Standard Thoracic Radiotherapy
45 Gy in 30 twice-daily fractions or 66 Gy in 33 once-daily fractions
- Radiation: Prophylactic Cranial Irradiation (PCI)
PCI will be strongly recommended for participants who achieve CR or PR after completion of chemoradiation treatment and have no clinical evidence of brain metastases
progression free survival (PFS) per RECIST 1.1 as assessed by blinded independent central review (BICR).
overall survival (OS).
safety and tolerability.
objective response rate (ORR) and duration of response (DOR) as assessed by BICR per RECIST 1.1.
the change from baseline (at Cycle 1) and the time to true deterioration (TTD) in global health status/quality of life (QoL), cough, chest pain, dyspnea, and physical functioning.
the effect of PD-L1 expression levels on the efficacy endpoints.
MSD K.K.
Showa University Hospital Institutional Review Board
United States/Canada/Mexico/Belgium/Estonia/France/Greece/Hungary/Italy/Lituania/Portugal/Rusia/Spain/Turkey/Ukraine/England/Australia/Republic of Korea/China
