A Safety Study of Oral Venetoclax in Combination With Intravenous Pembrolizumab in Adult Participants With Previously Untreated Non-Small Cell Lung Cancer (NSCLC) With High Programmed Cell Death Ligand-1 (PD-L1) Expression
- Conditions
- Non Small Cell Lung CancerCancer
- Interventions
- Registration Number
- NCT04274907
- Lead Sponsor
- AbbVie
- Brief Summary
Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. It is the most common form of lung cancer, accounting for around 85% of lung cancers. The purpose of this study is to evaluate the safety and efficacy (how well the study drug works against the disease) of venetoclax in combination with pembrolizumab in participants with NSCLC.
Venetoclax is a drug that kills cancer cells by blocking a protein (part of a cell) that allows cancer cells to stay alive. Pembrolizumab is approved drug for the treatment of NSCLC. It works with your immune system to help fight certain cancers. The study is split into two portions - dose escalation and randomization. Participants are assigned one of the three treatment groups to receive pembrolizumab alone or in combination with venetoclax. Each group receives a different treatment. Participants who are at least 18 years of age with a diagnosis of NSCLC will be enrolled. Around 100 participants will be enrolled in the study in approximately 44 sites across United States.
Participants will receive intravenous (IV) infusion of pembrolizumab alone or in combination with oral venetoclax tablets.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 2
- Histologically documented advanced or metastatic NSCLC with no known epidermal growth factor receptor (EGFR) sensitizing (activating) mutation or anaplastic lymphoma kinase (ALK) translocation.
- At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
- High PD-L1 tumor expression (tumor proportion score >= 50%) as determined by a Food and Drug Administration (FDA)-approved test.
- Willing to provide tissue biopsy sample prior to start of study.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Received prior systemic treatment for their advanced or metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
- History of or ongoing interstitial lung disease or pneumonitis that required oral or intravenous (IV) steroids.
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If a participant has signs/symptoms suggestive of SARS-CoV-2 infection, they should undergo molecular (e.g., polymerase chain reaction [PCR]) testing to rule out SARS-CoV-2 infection.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation Phase: Venetoclax + Pembrolizumab Venetoclax Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A. Dose Escalation Phase: Venetoclax + Pembrolizumab Pembrolizumab Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A. Randomization Phase: Venetoclax + Pembrolizumab Venetoclax Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A. Randomization Phase: Pembrolizumab Monotherapy Pembrolizumab Participants will receive pembrolizumab Dose A Randomization Phase: Venetoclax + Pembrolizumab Pembrolizumab Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A.
- Primary Outcome Measures
Name Time Method Number of Participants with Dose-Limiting Toxicities (DLTs) Up to 28 Days DLTs are adverse events that are considered to have a reasonable possibility of relationship to the administration of venetoclax and pembrolizumab and cannot be attributed by the investigator to a clearly identifiable cause such as disease progression, concurrent illness or concomitant medication.
Change in the Sum of the Longest Diameter (SLD) Up to 35 Cycles (Each Cycle is 21 Days) Change in the SLD is assessed by exposure-response modeling
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to 35 Cycles (Each Cycle is 21 Days) ORR will be defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR).
Area Under the Plasma Concentration-Time Curve Over Time from 0 to 24 (AUC0-24) of Venetoclax in Plasma Up to Cycle 1 (Each Cycle is 21 Days) Area Under the Plasma Concentration-time Curve (AUC) from 0-24 (AUC0-24)
Maximum Plasma Concentration (Cmax) of Venetoclax Up to Cycle 1 (Each Cycle is 21 Days) Maximum plasma concentration (Cmax) of venetoclax
Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax Up to Cycle 1 (Each Cycle is 21 Days) Time to maximum observed plasma concentration (Tmax) of venetoclax
Trial Locations
- Locations (39)
Arizona Oncology Associates, PC-HOPE (Rudasill) /ID# 216984
🇺🇸Tucson, Arizona, United States
St Jude Hospital dba St Joseph /ID# 212360
🇺🇸Santa Rosa, California, United States
Icri /Id# 217071
🇺🇸Whittier, California, United States
Georgia Regents University /ID# 217109
🇺🇸Augusta, Georgia, United States
Rush University Medical Center /ID# 212448
🇺🇸Chicago, Illinois, United States
University of Chicago DCAM /ID# 214319
🇺🇸Chicago, Illinois, United States
Fort Wayne Medical Oncology /ID# 214954
🇺🇸Fort Wayne, Indiana, United States
Central Maine Medical Center /ID# 216107
🇺🇸Lewiston, Maine, United States
Maryland Oncology Hematology /ID# 214131
🇺🇸Columbia, Maryland, United States
University of Massachusetts Ca /ID# 218744
🇺🇸Worcester, Massachusetts, United States
Univ of Mississippi Med Ctr /ID# 216429
🇺🇸Jackson, Mississippi, United States
Hackensack Univ Med Ctr /ID# 216484
🇺🇸Hackensack, New Jersey, United States
Atlantic Health System /ID# 217067
🇺🇸Morristown, New Jersey, United States
Overlook Medical Center /ID# 219108
🇺🇸Summit, New Jersey, United States
NYU Langone - Laura and Isaac Perlmutter Cancer Center /ID# 218077
🇺🇸New York, New York, United States
Weill Cornell Medical Center /ID# 216911
🇺🇸New York, New York, United States
University Hospitals Cleveland /ID# 212241
🇺🇸Cleveland, Ohio, United States
Prisma Health Cancer Institute - Faris /ID# 217946
🇺🇸Greenville, South Carolina, United States
The Ohio State University - The James /ID# 212298
🇺🇸Columbus, Ohio, United States
Thompson Cancer Survival Ctr /ID# 217076
🇺🇸Knoxville, Tennessee, United States
Massey Cancer Centre /ID# 212527
🇺🇸Richmond, Virginia, United States
Virginia Cancer Specialists /ID# 214328
🇺🇸Fairfax, Virginia, United States
Northwest Medical Specialties /ID# 218484
🇺🇸Tacoma, Washington, United States
Multicare Institute for Research and Innovation /ID# 217913
🇺🇸Tacoma, Washington, United States
Ingalls Memorial Hosp /ID# 214952
🇺🇸Harvey, Illinois, United States
Ashland-Bellefonte Cancer Ctr /ID# 218511
🇺🇸Ashland, Kentucky, United States
Allegheny General Hospital /ID# 214363
🇺🇸Pittsburgh, Pennsylvania, United States
Washington University-School of Medicine /ID# 212355
🇺🇸Saint Louis, Missouri, United States
Univ of Alabama at Birmingham /ID# 214180
🇺🇸Birmingham, Alabama, United States
AdventHealth Cancer Institute - Orlando /ID# 214444
🇺🇸Orlando, Florida, United States
University of Louisville /ID# 215195
🇺🇸Louisville, Kentucky, United States
Karmanos Cancer Institute /ID# 216986
🇺🇸Detroit, Michigan, United States
Henry Ford Health System /ID# 216385
🇺🇸Detroit, Michigan, United States
Methodist Estabrook Cancer Center /ID# 216910
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center /ID# 216754
🇺🇸Omaha, Nebraska, United States
University of Cincinnati Cancer Institute /ID# 216800
🇺🇸Cincinnati, Ohio, United States
Providence Cancer Center Oncology and Hematology Care - Westside Portland /ID# 215497
🇺🇸Portland, Oregon, United States
Utah Cancer Specialists /ID# 215496
🇺🇸Salt Lake City, Utah, United States
Houston Methodist Hospital - Scurlock Tower /ID# 215481
🇺🇸Houston, Texas, United States