Purpose

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).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 (CNS) 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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 progressive disease, physician decision or intolerable toxicity.
  • Biological: Pembrolizumab
    IV infusion
    Other names:
    • MK-3475
  • Drug: Carboplatin
    IV infusion
    Other names:
    • PARAPLATIN®
  • Drug: Paclitaxel
    IV infusion
    Other names:
    • TAXOL®
    • ONXAL™
  • Drug: Nab-paclitaxel
    IV infusion
    Other names:
    • ABRAXANE®
  • Drug: Olaparib
    Tablets
    Other names:
    • LYNPARZA®
  • Drug: Placebo
    Placebo to olaparib, tablets
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 progressive disease, physician decision or intolerable toxicity.
  • Biological: Pembrolizumab
    IV infusion
    Other names:
    • MK-3475
  • Drug: Carboplatin
    IV infusion
    Other names:
    • PARAPLATIN®
  • Drug: Paclitaxel
    IV infusion
    Other names:
    • TAXOL®
    • ONXAL™
  • Drug: Nab-paclitaxel
    IV infusion
    Other names:
    • ABRAXANE®
  • Drug: Placebo
    Placebo to olaparib, tablets

Recruiting Locations

MedStar Franklin Square Medical Center ( Site 0044)
Baltimore, Maryland 21237
Contact:
Study Coordinator
443-777-7364

More Details

NCT ID
NCT03976362
Status
Recruiting
Sponsor
Merck Sharp & Dohme Corp.

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@merck.com

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 progressive disease (PD), intolerable toxicities, or physician decision."

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.