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Substudy 3: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Participants With Advanced Non-small Cell Lung Cancer (NSCLC), Previously Treated With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Therapy (MK-3475-01C / KEYNOTE-01C)

Trial Status: Active

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-5890 and 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).

Inclusion 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 or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated - 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 28-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 prior to 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 prior to 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 prior to 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) - Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to 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


San Francisco
UCSF Medical Center-Mission Bay
Contact: UCSF Clinical Trials
Phone: 877-827-3222


University of Kentucky / Markey Cancer Center
Status: ACTIVE
Contact: Susanne Markesbery Arnold
Phone: 859-218-0131


Ohio State University Comprehensive Cancer Center
Status: ACTIVE

The Master screening protocol is MK-3475-U01 - NCT04165798

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Merck and Company Inc

  • Primary ID 3475-01C
  • Secondary IDs NCI-2020-03340, KEYNOTE-01C, MK-3475-01C, 2020-001629-29
  • ID NCT04165096