Purpose

This study is referred to as the "umbrella master protocol" for pembrolizumab (MK-3475) in the treatment of non-small cell lung cancer (NSCLC). This pembrolizumab NSCLC umbrella master protocol uses a platform design and consists of this master screening study and three substudies. Each substudy will enroll a different population of NSCLC participants. The goal of this umbrella master protocol is to screen potential participants with NSCLC for enrollment into 1 of 3 substudies. Participants must first enroll in this pembrolizumab master protocol study and undergo screening for NSCLC that will be used to assign them to participation in 1 of 3 pembrolizumab substudies.

Condition

Eligibility

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

Inclusion Criteria

  • Has histologically- or cytologically-confirmed diagnosis of Stage IV squamous or nonsquamous NSCLC
  • Participants with nonsquamous NSCLC who are 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
  • Has not received prior systemic treatment for their metastatic NSCLC
  • Is able to complete all screening procedures within the 28-day screening window
  • Has adequate organ function within 10 days of initiation of study treatment
  • Male participants must agree to use contraception and should refrain from donating sperm during the treatment period and:
  • Substudy 1: for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy
  • Substudies 2 and 3: for at least 120 days after study treatments
  • Female participants must not be pregnant or breastfeeding, and at least 1 of the following conditions apply:
  • Not a woman of childbearing potential (WOCBP), OR
  • A WOCBP who agrees to use contraception during the treatment period and:
  • Substudy 1: for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy.
  • Substudies 2 and 3: for at least 120 days after study treatment

*Substudies 1 and 2 Only:

- Has not received prior systemic treatment for their metastatic NSCLC

*Substudy 2 Only:

- Has a programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1%

*Substudy 3 Only:

- Has 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.

- Has progressive disease during/after platinum doublet chemotherapy

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 administration, or New York Heart Association Class III or IV congestive heart failure
  • Has a known history of HIV infection
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has had major surgery <3 weeks prior to first dose of study treatment
  • Is expected to require any other form of antineoplastic therapy while on study
  • 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
  • Previously 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

*Substudy 1 Only:

- Has symptomatic ascites or pleural effusion (if receiving pemetrexed; Alimta®; Eli Lilly)

- Has a history or current evidence of a gastrointestinal (GI) condition (e.g. inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications

- Is getting chemotherapy and has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, or peritoneal carcinomatosis

- Has pre-existing neuropathy that is moderate in intensity

- Is currently receiving either strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C8 (CYP2C8) that cannot be discontinued for the duration of the study

- Is currently receiving strong or moderate inducers of CYP3A4 or CYP2C8 that cannot be discontinued for the duration of the study

- Is unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), other than aspirin dose less than or equal to 1.3 gm/day for a 5-day period (8-day period for long acting agents such as peroxicam), for participants who will receive pemetrexed

- Is unable or unwilling to take folic acid or vitamin B12 supplementation, for participants who will receive pemetrexed

- Has a known sensitivity to any component of carboplatin, paclitaxel, pemetrexed or any of their excipients

*Substudies 1 and 2 Only:

- Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease

- Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), or anti-PD-L2 agent or prior therapy targeting other immunoregulatory receptors or mechanisms

*Substudy 3 Only:

- Has received prior therapy targeting other immuno-regulatory receptors or mechanisms, not including anti-PD-(L)1 agents

- Has participated in Substudies 1 or 2

Study Design

Phase
Study Type
Observational
Observational Model
Cohort
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
Prospective NSCLC Participants Male and female participants with histologically-confirmed diagnosis of squamous or nonsquamous NSCLC will be screened for participation in 1 of 3 pembrolizumab substudies.
  • Diagnostic Test: Tumor Imaging
    Participants will undergo tumor imaging using either a magnetic resonance imaging (MRI) scan or a computed tomography (CT) scan.
  • Procedure: Tumor Tissue Collection
    Participants without archival tumor tissue samples will undergo tumor tissue collection for newly obtained tumor tissue.
  • Procedure: Blood Sample Collection
    Participants will have blood samples drawn for analysis of: genetics ribonucleic acid (RNA) serum biomarker plasma biomarker circulating tumor DNA (ctDNA)

Recruiting Locations

MedStar Franklin Square Medical Center ( Site 0033)
Baltimore, Maryland 21237
Contact:
Study Coordinator
443-777-7364

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme Corp.

Study Contact

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

Detailed Description

The following 3 pembrolizumab substudies will evaluate the efficacy of different investigational agents in combination with pembrolizumab given in sequence or in combination with pembrolizumab PLUS chemotherapy:

- Substudy 1: A Phase 2, Umbrella Study with Rolling Arms of Investigational Agents with Pembrolizumab in Combination with Chemotherapy in Treatment-Naïve Patients with Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A) - NCT04165070

- Substudy 2: A Phase 2, Umbrella Study with Rolling Arms of Investigational Agents in Combination with Pembrolizumab in Treatment Naïve Patients with PD-L1 Positive Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01B) - NCT04165083

- Substudy 3: A Phase 2, Umbrella Study with Rolling Arms of Investigational Agents in Combination with Pembrolizumab in Patients with Advanced Non-small Cell Lung Cancer (NSCLC) Previously Treated with anti-PD-(L)1 Therapy (MK-3475-01C) - NCT04165096

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.