KEYMAKER-U01 Substudy 1: Efficacy and Safety Study of Pembrolizumab (MK-3475) Plus Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A)

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

KEYMAKER-U01 Substudy 1: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents With Pembrolizumab in Combination With Chemotherapy in Treatment-Naive Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04165070
• Other study ID #: 3475-01A
• Secondary ID: MK-3475-01AKEYMA
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 19, 2019
• Est. completion date: February 13, 2039

Study information

• Verified date: February 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) PLUS chemotherapy in combination with vibostolimab (MK-7684), boserolimab (MK-5890), MK-4830, or MK-0482 in treatment-naïve participants with advanced squamous or non-squamous NSCLC.

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

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 360
• Est. completion date: February 13, 2039
• Est. primary completion date: February 13, 2039
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

• 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 for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy

• 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 pembrolizumab and for at least 180 days after the last dose of 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 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 HIV infection

• Has a known history of Hepatitis B or known active Hepatitis C virus infection

• 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 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 preexisting neuropathy that is moderate in intensity

• 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

• 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

• 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

• 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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Carboplatin
IV infusion
• Paclitaxel
IV infusion
• Pemetrexed
IV infusion

Biological:
• Vibostolimab
IV infusion
• Boserolimab
IV infusion
• MK-4830
IV infusion
• MK-0482
IV Infusion

Locations

Country	Name	City	State
Hungary	Orszagos Koranyi Pulmonologiai Intezet ( Site 0060)	Budapest
Hungary	Petz Aladar Megyei Oktato Korhaz ( Site 0062)	Gyor	Gyor-Moson-Sopron
Hungary	Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0061)	Szolnok	Jasz-Nagykun-Szolnok
Israel	Soroka Medical Center ( Site 0072)	Beer-Sheva
Israel	Rambam Health Care Campus-Oncology ( Site 0076)	Haifa
Israel	Shaare Zedek Medical Center ( Site 0075)	Jerusalem
Israel	Meir Medical Center ( Site 0071)	Kfar-Saba
Israel	Rabin Medical Center ( Site 0074)	Petah Tikva
Israel	Chaim Sheba Medical Center ( Site 0070)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0077)	Tel Aviv
Italy	Azienda Ospedaliera Universitaria Careggi ( Site 0173)	Florence	Firenze
Italy	IRCCS Ospedale San Raffaele ( Site 0171)	Milano
Italy	Policlinico Gemelli di Roma ( Site 0174)	Roma	Lazio
Korea, Republic of	Seoul National University Bundang Hospital ( Site 0081)	Seongnam-si	Kyonggi-do
Korea, Republic of	Samsung Medical Center ( Site 0082)	Seoul
Korea, Republic of	Severance Hospital ( Site 0080)	Seoul
Poland	Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)	Gdansk	Pomorskie
Poland	Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)	Koszalin	Zachodniopomorskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier	Warszawa	Mazowieckie
Spain	ICO L Hospitalet ( Site 0090)	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Quiron Madrid ( Site 0091)	Pozuelo de Alarcon	Madrid
United States	MedStar Franklin Square Medical Center ( Site 0033)	Baltimore	Maryland
United States	Dana Farber Cancer Institute ( Site 0002)	Boston	Massachusetts
United States	Massachusetts General Hospital ( Site 0003)	Boston	Massachusetts
United States	Cleveland Clinic ( Site 0006)	Cleveland	Ohio
United States	The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C	Columbus	Ohio
United States	City of Hope ( Site 0014)	Duarte	California
United States	Sanford Fargo Medical Center ( Site 0039)	Fargo	North Dakota
United States	Banner MD Anderson Cancer Center ( Site 0001)	Gilbert	Arizona
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037)	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center ( Site 0009)	Houston	Texas
United States	Dartmouth Hitchcock Medical Center ( Site 0016)	Lebanon	New Hampshire
United States	University of Kentucky Markey Cancer Center ( Site 0019)	Lexington	Kentucky
United States	Laura and Isaac Perlmutter Cancer Center ( Site 0034)	New York	New York
United States	Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031)	Omaha	Nebraska
United States	Abramson Cancer Center of the University of Pennsylvania ( Site 0010)	Philadelphia	Pennsylvania
United States	UCSF Medical Center at Mission Bay ( Site 0007)	San Francisco	California
United States	Sanford Cancer Center ( Site 0038)	Sioux Falls	South Dakota
United States	Georgetown University ( Site 0036)	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Hungary,  Israel,  Italy,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: =30% decrease in the sum of diameters of target lesions) per RECIST 1.1.	Up to approximately 24 months
Secondary	Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS is defined as the time from first dose of study treatment until either the earliest date of documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD.	Up to approximately 24 months
Secondary	Number of Participants Who Experience One or More Adverse Events (AEs)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.	Up to approximately 27 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.	Up to approximately 24 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary