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JOURNAL ONKOLOGIE – STUDIE

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)

Rekrutierend

NCT-Nummer:
NCT03976323

Studienbeginn:
Juni 2019

Letztes Update:
12.04.2021

Wirkstoff:
Pembrolizumab, Pemetrexed, Carboplatin, Cisplatin, Olaparib

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations
(3 von 178)

InVo-Institut fuer Versorgungsforschung in der Onkologie ( Site 1514)
56068 Koblenz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +49261921569323
» Ansprechpartner anzeigen
Frontier Oncology ( Site 0080)
59102 Billings
United StatesAbgeschlossen» Google-Maps
Cancer Care Northwest ( Site 0071)
99216 Spokane Valley
United StatesAbgeschlossen» Google-Maps
Instituto do Cancer do Ceara ( Site 0201)
60430-230 Fortaleza
BrazilAktiv, nicht rekrutierend» Google-Maps
Centre de Sante et des Services Sociaux de Rimouski-Neigette ( Site 0104)
G5L 5T1 Rimouski
CanadaAbgeschlossen» Google-Maps
Korea University Guro Hospital ( Site 1008)
08308 Seoul
Korea, Republic ofAbgeschlossen» Google-Maps
Wielospecjalistyczny Szpital SPZOZ w Zgorzelcu ( Site 2404)
59-900 Zgorzelec
PolandAbgeschlossen» Google-Maps
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
02-781 Warszawa
PolandRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +48225463066
» Ansprechpartner anzeigen
Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 2000)
115478 Moscow
Russian FederationAktiv, nicht rekrutierend» Google-Maps
First Moscow State Medical University n.a. I.M.Sechenov ( Site 2024)
119991 Moscow
Russian FederationAktiv, nicht rekrutierend» Google-Maps
FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 2006)
125367 Moscow
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +74991901228
» Ansprechpartner anzeigen
Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary-Chemotherapy #1 ( Site
644013 Omsk
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +73812601037
» Ansprechpartner anzeigen
SBHI Samara Regional Clinical Oncology Dispensary ( Site 2016)
443031 Samara
Russian FederationAbgeschlossen» Google-Maps
SPb Central Clinical Railway Hospital ( Site 2003)
195271 Saint Petersburg
Russian FederationAbgeschlossen» Google-Maps
National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 2004)
197758 Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +78124399555
» Ansprechpartner anzeigen
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 2021)
420029 Kazan
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Ege Universitesi Tip Fakultesi ( Site 2109)
35040 Izmir
TurkeyAktiv, nicht rekrutierend» Google-Maps
Cherkasy Regional Oncology Dispensary ( Site 2211)
18009 Cherkasy
UkraineAktiv, nicht rekrutierend» Google-Maps
City Clinical Hosp.4 of DCC ( Site 2201)
49102 Dnipro
UkraineAktiv, nicht rekrutierend» Google-Maps
MI Precarpathian Clinical Oncology Center ( Site 2204)
76018 Ivano-Frankivsk
UkraineAktiv, nicht rekrutierend» Google-Maps
Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 2212)
61024 Kharkiv
UkraineAbgeschlossen» Google-Maps
Regional Centre of Oncology-Thoracic organs ( Site 2205)
61070 Kharkiv
UkraineAktiv, nicht rekrutierend» Google-Maps
PP PPC Acinus Medical and Diagnostic Centre ( Site 2209)
25006 Kropyvnitskiy
UkraineAktiv, nicht rekrutierend» Google-Maps
Medical Center Asklepion LLC ( Site 2234)
08173 Khodosivka
UkraineAktiv, nicht rekrutierend» Google-Maps
Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 2213)
03126 Kyiv
UkraineAbgeschlossen» Google-Maps
MI Odessa Regional Oncological Centre ( Site 2208)
65055 Odesa
UkraineAktiv, nicht rekrutierend» Google-Maps
Central City Clinical Hospital ( Site 2207)
88000 Uzhgorod
UkraineAktiv, nicht rekrutierend» Google-Maps
Medical Center Verum ( Site 2230)
03039 Kyiv
UkraineAktiv, nicht rekrutierend» Google-Maps
Kyiv City Clinical Oncology Centre ( Site 2210)
03115 Kyiv
UkraineAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Have a histologically or cytologically confirmed diagnosis nonsquamous NSCLC.

2. Have stage IV nonsquamous NSCLC.

3. Have confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma

kinase (ALK), or Proto-oncogene tyrosine-protein kinase (ROS1)-directed therapy is not

indicated.

4. Have measurable disease based on RECIST 1.1.

5. 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.

6. Have a life expectancy of at least 3 months.

7. 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.

8. Have not received prior systemic treatment for their advanced/metastatic NSCLC.

9. Have adequate organ function.

10. 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.

11. 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:

1. Has predominantly squamous cell histology NSCLC.

2. Has a known additional malignancy that is progressing or has progressed within the

past 3 years requiring active treatment.

3. Has known active central nervous system (CNS) metastases and/or carcinomatous

meningitis.

4. Has a severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its

excipients.

5. Has a known hypersensitivity to any components or excipients of cisplatin,

carboplatin, pemetrexed, or olaparib.

6. Has an active autoimmune disease that has required systemic treatment in past 2 years.

7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.

8. Has a known history of human immunodeficiency virus (HIV) infection, a known history

of hepatitis B infection, or known active hepatitis C virus infection.

9. Has interstitial lung disease, or history of pneumonitis requiring systemic steroids

for treatment.

10. Has received prior therapy with olaparib or with any other polyadenosine 5'

diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor.

11. 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).

12. Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features

suggestive of MDS/AML.

13. 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.

Studien-Rationale

Primary outcome:

1. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Time Frame - Up to approximately 3 years):
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.

2. Overall Survival (OS) (Time Frame - Up to approximately 5 years):
Overall survival is the time from the date of randomization to death due to any cause.

Secondary outcome:

1. Number of Participants Experiencing an Adverse Event (AE) (Time Frame - Up to approximately 5 years):
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.

2. Number of Participants Discontinuing Study Treatment Due to Adverse Event (AE) (Time Frame - Up to approximately 5 years):
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.

3. 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 (Time Frame - Baseline (at randomization) and Week 18 post-randomization):
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.

4. Change from Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score (Time Frame - Baseline (at randomization) and Week 18 post-randomization):
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.

5. Change from Baseline in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score (Time Frame - Baseline (at randomization) and Week 18 post-randomization):
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.

6. Change from Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score (Time Frame - Baseline (at randomization) and Week 18 post-randomization):
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.

7. Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score (Time Frame - Baseline (at randomization) and Week 18 post-randomization):
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.

8. Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score (Time Frame - Up to approximately 5 years):
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.

9. Time to True Deterioration (TTD) in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score (Time Frame - Up to approximately 5 years):
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.

10. Time to True Deterioration (TTD) in EORTC (QLQ-LC13 Chest Pain (Item 10) Scale Score (Time Frame - Up to approximately 5 years):
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.

11. Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score (Time Frame - Up to approximately 5 years):
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.

12. Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score (Time Frame - Up to approximately 5 years):
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.

Studien-Arme

  • Experimental: Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib
    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.
  • Active Comparator: Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed
    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.

Geprüfte Regime

  • Pembrolizumab (MK-3475 / KEYTRUDA® / ):
    IV infusion
  • Pemetrexed (ALIMTA®):
    IV infusion
  • Carboplatin (PARAPLATIN®):
    IV infusion
  • Cisplatin (PLATINOL® / PLATINOL®-AQ / ):
    IV infusion
  • Olaparib (LYNPARZA®):
    Tablets

Quelle: ClinicalTrials.gov


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