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Phase 3 N=851 Randomized Triple-blind Treatment

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)

Carcinoma, Squamous Cell, Non-small-cell Lung

Enrolled (actual)
851
Serious AEs
27.3%
Results posted
Nov 2024
Primary outcome: Primary: Progression-free Survival (PFS) — 8.3; 5.4 Months — p=0.0040

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Pembrolizumab (Biological); Carboplatin (Drug); Paclitaxel (Drug); Nab-paclitaxel (Drug); Olaparib (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Merck Sharp & Dohme LLC
Primary completion
Sep 2023

Outcome Measures

OutcomeResultp-value
PRIMARY
Progression-free Survival (PFS)
8.3; 5.4 0.0040 sig
PRIMARY
Overall Survival (OS)
19.1; 18.6 0.5481
SECONDARY
Number of Participants With One or More Adverse Events (AEs)
SECONDARY
Number of Participants Who Discontinued Study Intervention Due to an AE
SECONDARY
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/ Quality of Life (QoL) (Items 29 and 30) Combined Scale Score
-1.24; -1.62 0.8238
SECONDARY
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 (GHS)/Quality of Life (QoL) (Items 29 and 30) Scale Score
29.08; 29.01 0.3083
SECONDARY
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
2.42; 0.74 0.4686
SECONDARY
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
24.18; NA 0.9174
SECONDARY
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
6.35; 2.52 0.0245 sig
SECONDARY
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
NA; NA 0.2133
SECONDARY
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
-1.08; -1.25 0.9381
SECONDARY
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
NA; NA 0.8464
SECONDARY
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
-2.04; 0.77 0.0870
SECONDARY
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
22.80; NA 0.0020 sig

Summary

The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, vs. pembrolizumab plus maintenance olaparib placebo for the treatment of squamous NSCLC. The study's 2 primary hypotheses are: 1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to progression-free survival (PFS) per RECIST 1.1 by blinded independent clinical review (BICR). 2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to overall survival (OS). As of Amendment 07, there will be no further analyses for OS and patient-reported outcome assessments.

Eligibility Criteria

Inclusion Criteria

  • Have a histologically or cytologically confirmed diagnosis squamous NSCLC.
  • Have Stage IV squamous NSCLC.
  • Have measurable disease based on RECIST 1.1.
  • Have not received prior systemic treatment for their advanced/metastatic NSCLC.
  • 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.

  • 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 a life expectancy of at least 3 months.
  • Has 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 during the treatment period and for 180 days afterwards.

Exclusion Criteria

  • Has non-squamous 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 metastases and/or carcinomatous meningitis.
  • Has a known hypersensitivity to any components or excipients of carboplatin, paclitaxel or nab-paclitaxel, or olaparib.
  • Has a severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03976362). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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