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Study of Pembrolizumab With Maintenance Olaparib or Maintenance Pemetrexed in First-line (1L) Metastatic Nonsquamous Non-Small-Cell Lung Cancer (NSCLC) (MK-7339-006, KEYLYNK-006)

Primary Purpose

Carcinoma, Non-squamous Non-small-cell Lung

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Pembrolizumab

Pemetrexed

Carboplatin

Cisplatin

Olaparib

About this trial

This is an interventional treatment trial for Carcinoma, Non-squamous Non-small-cell Lung focused on measuring Lung cancer, PD-1, PD L1, PD L2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Have a histologically or cytologically confirmed diagnosis nonsquamous NSCLC.
Have stage IV nonsquamous NSCLC.
Have confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or Proto-oncogene tyrosine-protein kinase (ROS1)-directed therapy is not indicated.
Have measurable disease based on RECIST 1.1.
Have provided archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated.
Note: Adequacy of biopsy specimen for the above analyses must be confirmed by the central laboratory before the participant can start the induction phase. Submission of another tumor specimen may be required prior to enrolling the participant, if adequate tumor tissue was not provided the first time.
Have a life expectancy of at least 3 months.
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status assessed within 7 days prior to the administration of study intervention.
Have not received prior systemic treatment for their advanced/metastatic NSCLC.
Have adequate organ function.
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.
Male participants must refrain from donating sperm, and female participants must refrain from donating eggs to others or freeze/store for her own use during the treatment period and for 180 days afterwards.

Exclusion Criteria:

Has predominantly squamous cell histology NSCLC.
Has a known additional malignancy that is progressing or has progressed within the past 3 years requiring active treatment.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has a severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
Has a known hypersensitivity to any components or excipients of cisplatin, carboplatin, pemetrexed, or olaparib.
Has an active autoimmune disease that has required systemic treatment in past 2 years.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
Has a known history of human immunodeficiency virus (HIV) infection, a known history of hepatitis B infection, or known active hepatitis C virus infection.
Has interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment.
Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor.
Has received prior therapy with an agent directed to programmed cell death ligand 1 (PD-L1), anti PD-L2, or directed to a stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137).
Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
Has not completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.

Sites / Locations

Alabama Oncology Bruno Cancer Center ( Site 0001)
Northwest Alabama Cancer Center, PC ( Site 0002)
Disney Family Cancer Center ( Site 0005)
Boca Raton Regional Hospital ( Site 0018)
Mid-Florida Cancer Centers ( Site 0022)
Moffitt Cancer Center ( Site 0024)
Columbus Regional Research Institute ( Site 0098)
Mount Sinai Hospital Medical Center ( Site 0032)
Oncology of Northshore ( Site 0033)
Methodists Hospitals/Premier Oncology Hematology Associates ( Site 0036)
Medstar Good Samaritan Hospital ( Site 0040)
Barbara Ann Karmanos Cancer Institute ( Site 0041)
Hattiesburg Clinic ( Site 0045)
Frontier Oncology ( Site 0080)
Bozeman Health Deaconness Cancer Center ( Site 0046)
Waverly Hematology Oncology ( Site 0081)
Thompson Cancer Survival Center ( Site 2812)
University of Tennessee Medical Center Knoxville ( Site 0060)
Renovatio Clinical ( Site 0062)
Cancer Care Northwest ( Site 0071)
Hospital Italiano Regional del Sur ( Site 0509)
Hospital Britanico de Buenos Aires ( Site 0500)
Instituto Medico Rio Cuarto ( Site 0501)
Centro Oncológico de Rosario ( Site 0507)
Centro Medico San Roque ( Site 0506)
Hospital Italiano de Buenos Aires ( Site 0511)
Clínica Universitaria Reina Fabiola ( Site 0505)
Sanatorio Privado San Geronimo S.R.L ( Site 0510)
Liverpool Hospital ( Site 1201)
Southern Medical Day Care Centre ( Site 1200)
Townsville General Hospital ( Site 1202)
Monash Cancer Centre ( Site 1205)
Ordensklinikum Linz GmbH Elisabethinen ( Site 1307)
Klinikum Wels-Grieskirchen ( Site 1304)
Innsbruck LKH ( Site 1302)
Social Medical Center - Otto Wagner Hospital ( Site 1301)
Krankenhaus Nord - Klinik Floridsdorf ( Site 1300)
Hospital Sao Rafael ( Site 0212)
Instituto do Cancer do Ceara ( Site 0201)
Oncologica do Brasil ( Site 0210)
Hospital Tacchini ( Site 0208)
Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 0209)
Saint Gallen Instituto de Oncologia ( Site 0206)
YNOVA Pesquisa Clinica ( Site 0215)
Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0202)
Centro de Hematologia e Oncologia ( Site 0205)
Hospital de Base de Sao Jose de Rio Preto ( Site 0204)
Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0203)
Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0200)
Hospital Paulistano - Amil Clinical Research ( Site 0207)
Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0214)
Lions Gate Hospital ( Site 0106)
BC Cancer - Victoria ( Site 0109)
Queen Elizabeth II Health Sciences Centre ( Site 0107)
Grand River Hospital ( Site 0117)
Stronach Regional Cancer Centre ( Site 0101)
Health Sciences North Research Institute ( Site 0115)
CISSS de la Monteregie-Centre ( Site 0114)
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0105)
CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0110)
Centre de Sante et des Services Sociaux de Rimouski-Neigette ( Site 0104)
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0103)
Fundacion Colombiana de Cancerologia Clinica Vida ( Site 0604)
Clinica de la Costa Ltda. ( Site 0608)
Administradora Country S.A. ( Site 0603)
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0601)
Centre Hospitalier De Chauny ( Site 1411)
CHU Caen ( Site 1406)
CHU Angers ( Site 1405)
Institut De Cancerologie De Lorraine ( Site 1409)
Hopital Robert Schuman ( Site 1402)
Centre Jean Perrin ( Site 1407)
Centre Hospitalier de Pau ( Site 1412)
CHU de Rouen ( Site 1403)
Hopital d'Instruction des Armees Begin ( Site 1413)
Studienzentrum Aschaffenburg ( Site 1525)
Klinikum Bogenhausen Staedt. Klinikum Muenchen GmbH ( Site 1523)
Klinikum der LMU ( Site 1500)
Universitaetsklinikum Regensburg ( Site 1512)
Klinikum Wuerzburg Mitte gGmbH ( Site 1509)
Universitaetsklinikum Frankfurt ( Site 1513)
Pneumologische Lehrklinik Universitaet Goettingen ( Site 1501)
Universitaetsmedizin Goettingen ( Site 1507)
Universitaetsklinikum Bonn ( Site 1524)
Kliniken Essen Mitte ( Site 1517)
InVo-Institut fuer Versorgungsforschung in der Onkologie ( Site 1514)
Helios Klinikum Erfurt GmbH ( Site 1502)
Katholisches Marienkrankenhaus gGmbH ( Site 1522)
National Hospital Organization Nagoya Medical Center ( Site 0806)
Aichi Cancer Center Hospital ( Site 0803)
National Cancer Center Hospital East ( Site 0801)
Kanazawa University Hospital ( Site 0811)
Kanagawa Cancer Center ( Site 0807)
Sendai Kousei Hospital ( Site 0812)
Kansai Medical University Hospital ( Site 0804)
National Hospital Organization Kinki-chuo Chest Medical Center ( Site 0813)
Shizuoka Cancer Center Hospital and Research Institute ( Site 0802)
National Hospital Organization Kyushu Medical Center ( Site 0805)
Niigata Cancer Center Hospital ( Site 0808)
Okayama University Hospital ( Site 0810)
Osaka International Cancer Institute ( Site 0809)
The Cancer Institute Hospital of JFCR ( Site 0800)
Chungbuk National University Hospital ( Site 1002)
National Cancer Center ( Site 1006)
The Catholic University of Korea St. Vincent s Hospital ( Site 1003)
Ajou University Hospital ( Site 1004)
Gyeongsang National University Hospital ( Site 1005)
Asan Medical Center ( Site 1007)
Seoul National University Hospital ( Site 1000)
Korea University Guro Hospital ( Site 1008)
MidCentral DHB Palmerston North Hospital ( Site 1102)
Capital & Coast District Health Board - Wellington Hospital ( Site 1101)
Wielospecjalistyczny Szpital SPZOZ w Zgorzelcu ( Site 2404)
Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 2420)
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
Szpital Rejonowy im. dr Jozefa Rostka ( Site 2402)
Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc ( Site 2417)
Przychodnia Lekarska Komed ( Site 2416)
MED-POLONIA Sp. z o.o. ( Site 2419)
Cardiomed SRL Cluj-Napoca ( Site 2504)
S.C. Radiotherapy Center Cluj S.R.L ( Site 2507)
S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 2508)
Policlinica Oncomed SRL ( Site 2505)
Spitalul PDR Medlife ( Site 2509)
S.C.Focus Lab Plus S.R.L ( Site 2502)
Spitalul Clinic Judetean De Urgenta Constanta ( Site 2501)
SBHI Leningrad Regional Clinical Hospital ( Site 2002)
Moscow Regional Oncological Dispensary ( Site 2028)
Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 2000)
First Moscow State Medical University n.a. I.M.Sechenov ( Site 2024)
Moscow Research Oncology Institute named after P.A. Hertsen ( Site 2009)
FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 2006)
Nizhniy Novgorod Region Oncology Dispensary ( Site 2026)
Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary-Chemotherapy #1 ( Site
SBHI Samara Regional Clinical Oncology Dispensary ( Site 2016)
SPb Central Clinical Railway Hospital ( Site 2003)
National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 2004)
SPb SBHI City Clinical Oncological Dispensary ( Site 2001)
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 2021)
Hospital Universitario Quiron Madrid ( Site 1701)
Hospital Clinico Universitario de Valencia ( Site 1706)
Hospital del Mar ( Site 1702)
Hospital Universitario Nuestra Senora de Valme ( Site 1703)
Hospital Clinico Lozano Blesa ( Site 1700)
Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0907)
China Medical University Hospital ( Site 0904)
National Cheng Kung University Hospital ( Site 0905)
National Taiwan University Hospital ( Site 0900)
Mackay Memorial Hospital ( Site 0902)
Chang Gung Medical Foundation.Linkou Branch ( Site 0903)
Namik Kemal Universitesi Tip Fakultesi ( Site 2100)
Baskent Unv. Adana Uyg. ve Arast. Hastanesi ( Site 2101)
Gazi Universitesi Tip Fakultesi ( Site 2104)
Ankara Sehir Hastanesi ( Site 2105)
Bezmialem Vakif Univ. Tıp Fakultesi Hastanesi Tibbi Onkoloji Bolumu ( Site 2107)
Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 2103)
Ege Universitesi Tip Fakultesi ( Site 2109)
Erciyes Universitesi Tip Fakultesi ( Site 2108)
Samsun Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi ( Site 2106)
Cherkasy Regional Oncology Dispensary ( Site 2211)
City Clinical Hosp.4 of DCC ( Site 2201)
MI Precarpathian Clinical Oncology Center ( Site 2204)
Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 2212)
Regional Centre of Oncology-Thoracic organs ( Site 2205)
PP PPC Acinus Medical and Diagnostic Centre ( Site 2209)
Medical Center Asklepion LLC ( Site 2234)
Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 2213)
MI Odessa Regional Oncological Centre ( Site 2208)
Central City Clinical Hospital ( Site 2207)
Medical Center Verum ( Site 2230)
Kyiv City Clinical Oncology Centre ( Site 2210)
Barts Health NHS Trust - St Bartholomew s Hospital ( Site 1923)
Chelsea and Westminster Hospital ( Site 1901)
West Suffolk Hospitals NHS Trust ( Site 1919)
Colchester General Hospital ( Site 1911)
Birmingham Heartlands Hospital ( Site 1910)
Western General Hospital, Edinburgh ( Site 1924)
Singleton Hospital ( Site 1909)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib

Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed

Arm Description

For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m^2 IV on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Platinum chemotherapy, investigator's choice: carboplatin area under the curve (AUC) 5 mg/mL/min IV on Day 1 of 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m^2 IV on Day 1 of 21-day cycle (Cycles 1 through 4). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21-day cycle for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until progressive disease, physician decision or intolerable toxicity.

For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m^2 IV on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Platinum chemotherapy, investigator's choice: carboplatin area under the curve (AUC) 5 mg/mL/min IV on Day 1 of 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m^2 IV on Day 1 of 21-day cycle (Cycles 1 through 4). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21 day-cycle for up to 31 cycles PLUS maintenance pemetrexed IV 500 mg/m^2 on Day 1 of each 21-day cycle. In the Maintenance Phase, the participant continues to receive maintenance pemetrexed until progressive disease, physician decision or intolerable toxicity.

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

Progression-free survival is the time from the date of randomization until either documented disease progression or death due to any cause, whichever occurs first.

Overall Survival (OS)

Overall survival is the time from the date of randomization to death due to any cause.

Secondary Outcome Measures

Number of Participants Experiencing an Adverse Event (AE)

An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Number of Participants Discontinuing Study Treatment Due to Adverse Event (AE)

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 and 30) Scale Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 scores will be presented.

Change from Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score

The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-LC13 cough (Item 1) score will be presented.

Change from Baseline in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score

The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. Participant responses to the question "How was your chest pain?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-LC13 chest pain (Item 10) score will be presented.

Change from Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-LC13 dyspnea (Item 8) score will be presented.

Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented.

Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. TTD is defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in EORTC QLQ-C30 Items 29 and 30 scale scores.

Time to True Deterioration (TTD) in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score

The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. TTD is defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in cough EORTC QLQ-LC13 cough (Item 1) scale score.

Time to True Deterioration (TTD) in EORTC (QLQ-LC13 Chest Pain (Item 10) Scale Score

The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. Participant responses to the question "How was your chest pain?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. TTD is defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in EORTC QLQ-LC13 chest pain (Item 10) scale score.

Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. TTD is defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in EORTC QLQ-C30 dyspnea (Item 8) scale score.

Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. TTD is defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in EORTC QLQ-C30 physical functioning (Items 1 to 5) scale scores.

Full Information

NCT ID

NCT03976323

First Posted

June 3, 2019

Last Updated

September 6, 2023

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT03976323

Brief Title

Study of Pembrolizumab With Maintenance Olaparib or Maintenance Pemetrexed in First-line (1L) Metastatic Nonsquamous Non-Small-Cell Lung Cancer (NSCLC) (MK-7339-006, KEYLYNK-006)

Official Title

A Phase 3 Study of Pembrolizumab in Combination With Pemetrexed/Platinum (Carboplatin or Cisplatin) Followed by Pembrolizumab and Maintenance Olaparib vs Maintenance Pemetrexed in the First-Line Treatment of Participants With Metastatic Nonsquamous Non-Small-Cell Lung Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 28, 2019 (Actual)

Primary Completion Date

August 13, 2024 (Anticipated)

Study Completion Date

January 13, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, vs pembrolizumab plus maintenance pemetrexed for the treatment of nonsquamous NSCLC. The study's 2 primary hypotheses are: 1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) by blinded independent clinical review (BICR) and 2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to overall survival (OS).

Detailed Description

This study has 2 phases: an Induction Phase (4 Cycles) and a Maintenance Phase (Up to 31 cycles of pembrolizumab). In the Induction Phase, participants receive pembrolizumab plus pemetrexed plus platinum (carboplatin or cisplatin). In the Maintenance Phase, participants with a partial or complete disease response or with stable disease after completing four cycles of induction therapy and who meet eligibility criteria will be randomly assigned to receive pembrolizumab plus maintenance olaparib OR pembrolizumab plus maintenance pemetrexed. In the Maintenance Phase, participants receive pembrolizumab for up to 31 cycles plus maintenance olaparib OR maintenance pemetrexed until progressive disease (PD), intolerable toxicities, or physician decision.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Non-squamous Non-small-cell Lung

Keywords

Lung cancer, PD-1, PD L1, PD L2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1005 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib

Arm Type

Experimental

Arm Description

Arm Title

Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed

Arm Type

Active Comparator

Arm Description

For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m^2 IV on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Platinum chemotherapy, investigator's choice: carboplatin area under the curve (AUC) 5 mg/mL/min IV on Day 1 of 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m^2 IV on Day 1 of 21-day cycle (Cycles 1 through 4). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21 day-cycle for up to 31 cycles PLUS maintenance pemetrexed IV 500 mg/m^2 on Day 1 of each 21-day cycle. In the Maintenance Phase, the participant continues to receive maintenance pemetrexed until progressive disease, physician decision or intolerable toxicity.

Intervention Type

Biological

Intervention Name(s)

Pembrolizumab

Other Intervention Name(s)

MK-3475, KEYTRUDA®

Intervention Description

IV infusion

Intervention Type

Drug

Intervention Name(s)

Pemetrexed

Other Intervention Name(s)

ALIMTA®

Intervention Description

IV infusion

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

PARAPLATIN®

Intervention Description

IV infusion

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

PLATINOL®, PLATINOL®-AQ

Intervention Description

IV infusion

Intervention Type

Drug

Intervention Name(s)

Olaparib

Other Intervention Name(s)

LYNPARZA®

Intervention Description

Tablets

Primary Outcome Measure Information:

Title

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

Description

Progression-free survival is the time from the date of randomization until either documented disease progression or death due to any cause, whichever occurs first.

Time Frame

Up to approximately 3 years

Title

Overall Survival (OS)

Description

Overall survival is the time from the date of randomization to death due to any cause.

Time Frame

Up to approximately 5 years

Secondary Outcome Measure Information:

Title

Number of Participants Experiencing an Adverse Event (AE)

Description

Time Frame

Up to approximately 5 years

Title

Number of Participants Discontinuing Study Treatment Due to Adverse Event (AE)

Description

Time Frame

Up to approximately 5 years

Title

Description

Time Frame