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JOURNAL ONKOLOGIE – STUDIE

A Study of Pembrolizumab (MK-3475) With or Without Maintenance Olaparib in First-line Metastatic Squamous Non-small Cell Lung Cancer (NSCLC, MK-7339-008/KEYLYNK-008)

Rekrutierend

NCT-Nummer:
NCT03976362

Studienbeginn:
Juni 2019

Letztes Update:
12.04.2021

Wirkstoff:
Pembrolizumab, Carboplatin, Paclitaxel, Nab-Paclitaxel, Olaparib, Placebo

Indikation (Clinical Trials):
Carcinoma, Squamous Cell

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 1564)
56068 Koblenz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +49261921569323
» Ansprechpartner anzeigen
Frontier Oncology ( Site 0052)
59102 Billings
United StatesAbgeschlossen» Google-Maps
Cancer Care Northwest ( Site 0083)
99216 Spokane Valley
United StatesAbgeschlossen» 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
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
Cherkasy Regional Oncology Dispensary ( Site 2225)
18009 Cherkasy
UkraineAktiv, nicht rekrutierend» Google-Maps
City Clinical Hosp.4 of DCC ( Site 2215)
49102 Dnipro
UkraineAktiv, nicht rekrutierend» Google-Maps
MI Precarpathian Clinical Oncology Center ( Site 2218)
76018 Ivano-Frankivsk
UkraineAktiv, nicht rekrutierend» Google-Maps
Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 2226)
61024 Kharkiv
UkraineAbgeschlossen» Google-Maps
Regional Centre of Oncology-Thoracic organs ( Site 2219)
61070 Kharkiv
UkraineAktiv, nicht rekrutierend» Google-Maps
PP PPC Acinus Medical and Diagnostic Centre ( Site 2223)
25006 Kropyvnytskyi
UkraineAktiv, nicht rekrutierend» Google-Maps
Medical Center Asklepion LLC ( Site 2243)
08173 Khodosivka
UkraineAktiv, nicht rekrutierend» Google-Maps
Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 2227)
03126 Kyiv
UkraineAbgeschlossen» Google-Maps
MI Odessa Regional Oncological Centre ( Site 2222)
65055 Odesa
UkraineAktiv, nicht rekrutierend» Google-Maps
Central City Clinical Hospital ( Site 2221)
88000 Uzhgorod
UkraineAktiv, nicht rekrutierend» Google-Maps
Medical Center Verum ( Site 2228)
03039 Kyiv
UkraineAktiv, nicht rekrutierend» Google-Maps
Kyiv City Clinical Oncology Centre ( Site 2224)
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

carboplatin plus a taxane (paclitaxel or nab-paclitaxel). 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 olaparib placebo. In the Maintenance Phase, participants randomly assigned to

receive pembrolizumab for up to 31 cycles plus maintenance olaparib OR maintenance olaparib

placebo until centrally verified progressive disease (PD), intolerable toxicities, or

physician decision."

Ein-/Ausschlusskriterien

Inclusion Criteria:

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

2. Have Stage IV squamous NSCLC.

3. Have measurable disease based on RECIST 1.1.

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

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 receive study intervention(s).

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 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

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

8. Has adequate organ function.

9. 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.

10. Male participants must refrain from donating sperm during the treatment period and for

180 days afterwards.

Exclusion Criteria:

1. Has non-squamous 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 metastases and/or carcinomatous meningitis.

4. Has a known hypersensitivity to any components or excipients of carboplatin,

paclitaxel or nab-paclitaxel, or olaparib.

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

excipients.

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.

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 With One or More Adverse Events (AEs) (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 intervention due to adverse events (AEs) (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 European Organization for Research and Treatment of Cancer (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 European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (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 European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (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. The change from baseline in EORTC QLQ-LC13 dyspnea (Item 8) score will be presented. A lower score indicates a better outcome.

7. Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (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 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 - 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 was 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 Items 29 and 30 scale scores.

9. Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (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 was 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 scale score.

10. Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (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 was 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 chest pain scale score.

11. Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (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 was 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 Item 8 scale score.

12. Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (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 was 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 physical functioning Items 1 to 5 scale scores.

Studien-Arme

  • Experimental: Pembrolizumab + Carboplatin + Taxane + Olaparib
    For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). 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 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 centrally verified progressive disease, physician decision or intolerable toxicity.
  • Active Comparator: Pembrolizumab + Carboplatin + Taxane + Olaparib Placebo
    For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). 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 for up to 31 cycles PLUS matching maintenance olaparib placebo twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib placebo until centrally verified progressive disease, physician decision or intolerable toxicity.

Geprüfte Regime

  • Pembrolizumab (MK-3475):
    IV infusion
  • Carboplatin (PARAPLATIN®):
    IV infusion
  • Paclitaxel (TAXOL® / ONXAL™ / ):
    IV infusion
  • Nab-paclitaxel (ABRAXANE®):
    IV infusion
  • Olaparib (LYNPARZA®):
    Tablets
  • Placebo:
    Placebo to olaparib, tablets

Quelle: ClinicalTrials.gov


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