Clinical trial NCT04274907: 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
Official title: A Phase 1b Study of Venetoclax in Combination With Pembrolizumab in Subjects With Previously Untreated NSCLC Whose Tumors Have High PD-L1 Expression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Cancer
Keywords: Non Small Cell Lung Cancer (NSCLC)
Cancer
Venetoclax
Pembrolizumab
PD-L1 Expression
ABT-199
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-02-18
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: Up to 28 Days
measure: Change in the Sum of the Longest Diameter (SLD)
timeFrame: Up to 35 Cycles (Each Cycle is 21 Days)
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Venetoclax
timeFrame: Up to Cycle 1 (Each Cycle is 21 Days)
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
timeFrame: Up to Cycle 1 (Each Cycle is 21 Days)
measure: Area Under the Plasma Concentration-Time Curve Over Time from 0 to 24 (AUC0-24) of Venetoclax in Plasma
timeFrame: Up to Cycle 1 (Each Cycle is 21 Days)
measure: Objective Response Rate (ORR)
timeFrame: Up to 35 Cycles (Each Cycle is 21 Days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham /ID# 214180
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC-HOPE (Rudasill) /ID# 216984
state: Arizona
city: Santa Rosa
country: United States
facility: St Jude Hospital dba St Joseph /ID# 212360
state: California
city: Whittier
country: United States
facility: Icri /Id# 217071
state: California
city: Orlando
country: United States
facility: AdventHealth Cancer Institute - Orlando /ID# 214444
state: Florida
city: Augusta
country: United States
facility: Georgia Regents University /ID# 217109
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center /ID# 212448
state: Illinois
city: Chicago
country: United States
facility: University of Chicago DCAM /ID# 214319
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hosp /ID# 214952
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology /ID# 214954
state: Indiana
city: Ashland
country: United States
facility: Ashland-Bellefonte Cancer Ctr /ID# 218511
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville /ID# 215195
state: Kentucky
city: Lewiston
country: United States
facility: Central Maine Medical Center /ID# 216107
state: Maine
city: Columbia
country: United States
facility: Maryland Oncology Hematology /ID# 214131
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Ca /ID# 218744
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute /ID# 216986
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System /ID# 216385
state: Michigan
city: Jackson
country: United States
facility: Univ of Mississippi Med Ctr /ID# 216429
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 212355
state: Missouri
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center /ID# 216910
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center /ID# 216754
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack Univ Med Ctr /ID# 216484
state: New Jersey
city: Morristown
country: United States
facility: Atlantic Health System /ID# 217067
state: New Jersey
city: Summit
country: United States
facility: Overlook Medical Center /ID# 219108
state: New Jersey
city: New York
country: United States
facility: NYU Langone - Laura and Isaac Perlmutter Cancer Center /ID# 218077
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center /ID# 216911
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute /ID# 216800
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland /ID# 212241
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University - The James /ID# 212298
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Center Oncology and Hematology Care - Westside Portland /ID# 215497
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny General Hospital /ID# 214363
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Faris /ID# 217946
state: South Carolina
city: Knoxville
country: United States
facility: Thompson Cancer Survival Ctr /ID# 217076
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Hospital - Scurlock Tower /ID# 215481
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists /ID# 215496
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists /ID# 214328
state: Virginia
city: Richmond
country: United States
facility: Massey Cancer Centre /ID# 212527
state: Virginia
city: Tacoma
country: United States
facility: Multicare Institute for Research and Innovation /ID# 217913
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties /ID# 218484
state: Washington
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: