Clinical trial NCT04165083: KEYMAKER-U01 Substudy 2: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Treatment-naïve Participants With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Positive Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01B/KEYMAKER-U01B)
Official title: KEYMAKER-U01 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Programmed Cell Death Receptor 1 (PD-1, PD1)
Programmed Cell Death Receptor Ligand 1 (PD-L1, PDL1)
Programmed Cell Death Receptor Ligand 2 (PD-L2, PDL2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-11-15
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-4830 in treatment-naïve participants with advanced squamous or non-squamous NSCLC that is PD-L1 positive.

This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

The pembrolizumab+ MK-0482 arm was added with Amendment 6.

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

Eligibility 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
* Has not received prior systemic treatment for metastatic NSCLC
* Has programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%
* 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 (noninfectious) 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 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)
* Has received a live vaccine within 30 days before the first dose of study treatment. Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed
* 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 receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or prior therapy targeting other immuno-regulatory receptors or mechanisms
* 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 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

Primary outcomes:
measure: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 24 months
measure: Number of Participants Who Experience One or More Adverse Events (AEs)
timeFrame: Up to approximately 27 months
measure: Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center ( Site 0001)
state: Arizona
city: Duarte
country: United States
facility: City of Hope ( Site 0014)
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mission Bay ( Site 0007)
state: California
city: Washington
country: United States
facility: Georgetown University ( Site 0036)
state: District of Columbia
city: Lexington
country: United States
facility: University of Kentucky Markey Cancer Center ( Site 0019)
state: Kentucky
city: Baltimore
country: United States
facility: MedStar Franklin Square Medical Center ( Site 0033)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital ( Site 0003)
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute ( Site 0002)
state: Massachusetts
city: Omaha
country: United States
facility: Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031)
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center ( Site 0016)
state: New Hampshire
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037)
state: New Jersey
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0034)
state: New York
city: Fargo
country: United States
facility: Sanford Fargo Medical Center ( Site 0039)
state: North Dakota
city: Cleveland
country: United States
facility: Cleveland Clinic ( Site 0006)
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center ( Site 0015)
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania ( Site 0010)
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center ( Site 0038)
state: South Dakota
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center ( Site 0009)
state: Texas
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz ( Site 0062)
state: Gyor-Moson-Sopron
city: Szolnok
country: Hungary
facility: Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0061)
state: Jasz-Nagykun-Szolnok
city: Budapest
country: Hungary
facility: Orszagos Koranyi Pulmonologiai Intezet ( Site 0060)
city: Beer-Sheva
country: Israel
facility: Soroka Medical Center ( Site 0072)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology ( Site 0076)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 0075)
city: Kfar-Saba
country: Israel
facility: Meir Medical Center ( Site 0071)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 0074)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 0070)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0077)
city: Florence
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi ( Site 0173)
state: Firenze
city: Roma
country: Italy
facility: Policlinico Gemelli di Roma ( Site 0174)
state: Lazio
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele ( Site 0171)
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital ( Site 0081)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Severance Hospital ( Site 0080)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 0082)
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier
state: Mazowieckie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)
state: Pomorskie
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)
state: Zachodniopomorskie
city: Hospitalet de Llobregat
country: Spain
facility: ICO L Hospitalet ( Site 0090)
state: Barcelona
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Madrid ( Site 0091)
state: Madrid
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: