Purpose

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-5890 or MK-4830 in participants with advanced squamous or non-squamous NSCLC that have been previously treated with anti-PD-L1 therapy. This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

Condition

Eligibility

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

Criteria


Inclusion:

- Has a histologically- or cytologically-confirmed diagnosis of Stage IV squamous or
non-squamous NSCLC

- Has non-squamous NSCLC and is not eligible for an approved targeted therapy

- Is able to provide archival tumor tissue sample collected either within 5 years or
within the interval from completion of last treatment but before entering the
screening period or newly obtained core or excisional biopsy of a tumor lesion not
previously irradiated obtained within 90 days of treatment initiation

- Have progressed on treatment with an anti-PD-(L)1 monoclonal antibody (mAb)
administered either as monotherapy, or in combination with other checkpoint inhibitors
or other therapies

- Have progressive disease (PD) during/after platinum doublet chemotherapy

- Is able to complete all screening procedures within the 35-day screening window

- Male participants must agree to use contraception and refrain from donating sperm
during the treatment period and for at least 120 days after the last dose of study
treatment

- Female participants must not be pregnant or breastfeeding, and at least one of the
following conditions apply:

1. Not a woman of childbearing potential (WOCBP) OR

2. A WOCBP who agrees to use contraception during the treatment period and for at
least 120 days after the last dose of study treatment

- Has adequate organ function within 10 days of initiation of study treatment

Exclusion Criteria:

- Has a diagnosis of small cell lung cancer

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days before the first dose of study treatment

- Has a known additional malignancy that is progressing or has required active treatment
within the past 2 years

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis

- Has an active autoimmune disease that has required systemic treatment in the past 2
years

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis

- Has an active infection requiring systemic therapy

- Has clinically significant cardiac disease, including unstable angina, acute
myocardial infarction within 6 months from Day 1 of study treatment, or New York Heart
Association Class III or IV congestive heart failure

- Has a known history of Human Immunodeficiency Virus (HIV) infection

- Has a known history of Hepatitis B or known active Hepatitis C virus infection

- Has known psychiatric or substance abuse disorders that would interfere with
cooperating with the requirements of the study

- Has had major surgery <3 weeks before the first dose of study treatment

- Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months
of the first dose of study treatment

- Has received a live vaccine within 30 days before the first dose of study treatment

- Has received any prior immunotherapy and was discontinued from that treatment due to a
severe or worse immune-related adverse event (irAE)

- Has had chemotherapy or biological cancer therapy within 4 weeks before the first dose
of study treatment or has not recovered to Common Terminology Criteria for Adverse
Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered
more than 4 weeks before the first dose of study treatment (including participants who
had previous immunomodulatory therapy with residual irAEs)

- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks before the first dose of
study treatment

- Has participated in Substudies 1 or 2

- Has had a severe hypersensitivity reaction to treatment with monoclonal antibodies
(including pembrolizumab) and/or any of their excipients

- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study treatment

- Has had an allogenic tissue/solid organ transplant

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Pembrolizumab + MK-5890
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-5890 IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (┬▒30 minutes) before infusion of MK-5890 with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
  • Biological: Pembrolizumab
    IV infusion
    Other names:
    • KEYTRUDA┬«
    • MK-3475
    • SCH 900475
  • Biological: MK-5890
    IV infusion
  • Drug: diphenhydramine
    PO
  • Drug: acetaminophen
    PO
Experimental
Pembrolizumab + MK-4830
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-4830 IV for a maximum of 35 cycles (approximately 2 years).
  • Biological: Pembrolizumab
    IV infusion
    Other names:
    • KEYTRUDA┬«
    • MK-3475
    • SCH 900475
  • Biological: MK-4830
    IV infusion

More Details

Status
Active, not recruiting
Sponsor
Merck Sharp & Dohme Corp.

Study Contact

Detailed Description

The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798

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.