Clinical trial NCT04165798: KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)
Official title: KEYMAKER-U01 Master Study: A Phase 1/2, Umbrella Study With Rolling Arms of Investigational Agents, Pembrolizumab, and Chemotherapy, Alone or in Combination, in Participants With Non-small Cell Lung Cancer (NSCLC)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2019-11-18
Enrollment: 1065
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Male and female participants with histologically-confirmed diagnosis of squamous or nonsquamous NSCLC

Brief summary: 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 seven 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 7 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 7 pembrolizumab substudies.

Detailed description: The following 7 pembrolizumab substudies will evaluate the efficacy of different investigational agents in combination with pembrolizumab given in sequence or in combination with pembrolizumab PLUS chemotherapy:

* KEYMAKER-U01 Substudy 01A: A Phase 1/2, Umbrella Study With Rolling Arms of Investigational Agents, With Pembrolizumab With or Without Chemotherapy in Treatment-Naive Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A) - NCT04165070
* 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) (MK-3475-01B) - NCT04165083
* KEYMAKER-U01 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
* KEYMAKER-U01 Substudy 01E: A Phase 2 Umbrella Study With Rolling Arms of Investigational Agents With or Without Chemotherapy in Combination With Pembrolizumab in Treatment of Participants With Newly Diagnosed Resectable Stages II-IIIB (N2) Non-small Cell Lung Cancer (NSCLC) (MK-3475-01E) - NCT06788912
* KEYMAKER-U01 Substudy 01G: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents in Combination With Pembrolizumab With or Without Platinum-based Chemotherapy in Treatment-Naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01G) - NCT06731907
* KEYMAKER-U01 Substudy 01F: A Phase 1b/2 Umbrella Study With Rolling Arms of Investigational Agents for Second-line Treatment of Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations
* KEYMAKER-U01 Substudy 01H: A Phase 2, Randomized, Umbrella Study With Rolling Arms of Investigational Agents in Participants with Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H) - NCT06780085
* KEYMAKER-U01 Substudy 01I: A Phase 2, Randomized, Umbrella Study With Rolling Arms of Investigational Agents in Participants With Previously Treated Stage IV Squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01I) - NCT06780098

Eligibility criteria: 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 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 their metastatic NSCLC
* 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

Exclusion Criteria:

* Has preexisting neuropathy that is moderate in intensity
* Has received a live or live-attenuated 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
* 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 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 an active autoimmune disease that has required systemic treatment in the past 2 years
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has an active infection requiring systemic therapy
* Has a known history of HIV infection
* Has a known history of Hepatitis B or known active Hepatitis C virus infection
* Has had an allogenic tissue/solid organ transplant

Primary outcomes:
measure: Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Level: Tumor Proportion Score (TPS) <1% vs. TPS =1%
timeFrame: Up to approximately 1 month
measure: Tumor Histology Status: Squamous Non-small Cell Lung Cancer (NSCLC) vs. Nonsquamous NSCLC
timeFrame: Up to approximately 1 month
Secondary outcomes:
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 Main ( 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: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele ( Site 0171)
city: Roma
country: Italy
facility: Policlinico Gemelli di Roma ( Site 0174)
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 ( Site 0151)
state: Mazowieckie
city: Gdansk
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: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona ( Site 0092)
city: Madrid
country: Spain
facility: Hospital Universitario Quiron Madrid ( Site 0091)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: