Unresectable, Locally Advanced, Stage III NSCLC
Conditions
Interventions
- Arm A - Participants will receive pembrolizumab 200 mg IV Q3W in combination with 3 cycles of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy (60 Gy in 2 Gy fractions
during Cycles 2 and 3) followed by pembrolizumab plus matching olaparib placebo for 12 months or until specific discontinuation criteria are met.
- Arm B - Participants will receive pembrolizumab 200
during Cycles 2 and 3) followed by pembrolizumab plus olaparib (300 mg BID) for 12 months or until specific discontinuation criteria are met.
- Arm C - Participants will receive 3 cycles of platinum d
during Cycles 2 and 3) followed by durvalumab 10 mg/kg Q2W for 12 months or until specific discontinuation criteria are met.
Sponsors
MSD K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Has pathologically (histologically or cytologically) confirmed diagnosis of NSCLC 2) Has Stage IIIA, IIIB, or IIIC NSCLC by American Joint Committee on Cancer Version 8 3) Is unable to undergo surgery with curative intent for Stage III NSCLC 4) Has no evidence of metastatic disease indicating Stage IV NSCLC 5) Has measurable disease as defined by RECIST 1.1 6) Has not received prior treatment (chemotherapy, targeted therapy or radiotherapy) for Stage III NSCLC; participants who have received neoadjuvant and/or adjuvant therapy for early stage disease are not eligible 7) Has provided a tumor tissue sample (tissue biopsy [core, incisional, or excisional]) 8) Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 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) A male participant must agree to use contraception and refrain from donating sperm during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention unless confirmed to be azoospermic (vasectomized or secondary to medical cause). The length of time required to continue contraception for each study intervention is as follows: Olaparib, platinum doublet, and radiotherapy: 90 days 11) A female participant is eligible to participate if she is not pregnant, not breastfeeding, and agrees to use contraception and refrain from donating eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during the treatment period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees to abstain from breastfeeding during the study intervention period and for at least 120 days after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows : Pembrolizumab: 120 days ; Olaparib, platinum doublet, and radiotherapy: 180 days 12) Has a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. 13) Has had her medical history, menstrual history, and recent sexual activity reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy. 14) Has adequate pulmonary function tests 15) Has adequate organ function 16) Has provided written informed consent
Exclusion criteria
Exclusion criteria: 1) Has small cell lung cancer or a mixed tumor with presence of small cell elements 2) Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML 3) Has had documented weight loss >10% (from baseline) in the preceding 3 months 4) Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or for breast cancer 5) Has received prior therapy with an anti-programmed cell death 1 (ant-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 co-inhibitory T-cell receptor 6) Has received prior therapy with olaparib or with any other polyadenosine 5'diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor 7) Has had major surgery =Grade 3) to study intervention and/or any of its excipients 20) Has an active autoimmune disease that has required systemic treatment in past 2 years 21) Has a history of (noninfectious) pneumonitis/interstitial lung disease th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - PFS: the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first - OS:the time from randomization to death due to any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety and tolerability ORR and DOR per RECIST 1.1 as assessed by BICR. Global health status/QoL, cough, chest pain, dyspnea, physical functioning, and role functioning following treatment | — |
Countries
Asia except Japan, Europe, Japan, North America, South America
Outcome results
None listed