Clinical trial NCT04165070: KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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: 2019-11-15
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Only participants in Part A will be randomized.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) with or without chemotherapy in combination with vibostolimab (MK-7684), boserolimab (MK-5890), MK-4830, MK-0482, I-DXd, or HER3-DXd in treatment-naïve participants with advanced squamous or non-squamous NSCLC.

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

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

Eligibility criteria: Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* 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 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
* Is able to complete all screening procedures within the 35-day screening window for Part A and 28-day screening window for Part B

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* 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 administration, or New York Heart Association Class III or IV congestive heart failure
* Has a known history of human immunodeficiency virus (HIV) infection. Well-controlled HIV with anti-retroviral therapy (ART) is not excluded
* Has a known history of Hepatitis B (HPV) or known active Hepatitis C virus infection. Hepatitis B surface antigen (HBsAg) positive is eligible if on HBV antiviral therapy for at least 4 weeks and HBV viral load is undetectable prior to randomization
* Has had major surgery \<3 weeks before the first dose of study treatment
* Is expected to require any other form of antineoplastic therapy while on study
* 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 preexisting neuropathy that is moderate in intensity
* Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease
* 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
* 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. 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 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
* Previously had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
* Has had an allogenic tissue/solid organ transplant

Primary outcomes:
measure: Part A: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 24 months
measure: Part B: Number of Participants Who Experience One or More Adverse Events (AEs)
timeFrame: Up to approximately 27 months
measure: Part B: Number of Participants Who Discontinue Study Intervention Due to an Adverse Event (AE)
timeFrame: Up to approximately 24 months
measure: Part B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)
timeFrame: Up to approximately 3 Weeks
Secondary outcomes:
measure: Part A: Progression-Free Survival (PFS) According to RECIST 1.1
timeFrame: Up to approximately 24 months
measure: Part A: Number of Participants Who Experience One or More AEs
timeFrame: Up to approximately 27 months
measure: Part A: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 24 months
measure: Part B: ORR per RECIST 1.1 as assessed by blinded independent central review (BICR)
timeFrame: Up to approximately 24 months
measure: Part B: Duration of Response (DOR) per RECIST 1.1 as assessed by BICR
timeFrame: Up to approximately 24 months
measure: Part B: Cmax of I-DXd
timeFrame: At designated time points up to approximately 2 years
measure: Part B: Cmax of HER3-DXd
timeFrame: At designated time points up to approximately 2 years
measure: Part B: Cmax of pembrolizumab
timeFrame: At designated time points up to approximately 2 years
measure: Part B: Ctrough of I-DXd
timeFrame: At designated time points up to approximately 2 years
measure: Part B: Ctrough of HER3-DXd
timeFrame: At designated time points up to approximately 2 years
measure: Part B: Ctrough of pembrolizumab
timeFrame: At designated time points up to approximately 2 years
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 ( 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: The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( 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: Madrid
country: Spain
facility: Hospital Universitario Quiron Madrid ( Site 0091)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: