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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

Primary Purpose

Non Small Cell Lung Cancer, Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Venetoclax
Pembrolizumab
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring Non Small Cell Lung Cancer (NSCLC), Cancer, Venetoclax, Pembrolizumab, PD-L1 Expression, ABT-199

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Univ of Alabama at Birmingham /ID# 214180
  • Arizona Oncology Associates, PC-HOPE (Rudasill) /ID# 216984
  • St Jude Hospital dba St Joseph /ID# 212360
  • Icri /Id# 217071
  • AdventHealth Cancer Institute - Orlando /ID# 214444
  • Georgia Regents University /ID# 217109
  • Rush University Medical Center /ID# 212448
  • University of Chicago DCAM /ID# 214319
  • Ingalls Memorial Hosp /ID# 214952
  • Fort Wayne Medical Oncology /ID# 214954
  • Ashland-Bellefonte Cancer Ctr /ID# 218511
  • University of Louisville /ID# 215195
  • Central Maine Medical Center /ID# 216107
  • Maryland Oncology Hematology /ID# 214131
  • University of Massachusetts Ca /ID# 218744
  • Karmanos Cancer Institute /ID# 216986
  • Henry Ford Health System /ID# 216385
  • Univ of Mississippi Med Ctr /ID# 216429
  • Washington University-School of Medicine /ID# 212355
  • Methodist Estabrook Cancer Center /ID# 216910
  • University of Nebraska Medical Center /ID# 216754
  • Hackensack Univ Med Ctr /ID# 216484
  • Atlantic Health System /ID# 217067
  • Overlook Medical Center /ID# 219108
  • NYU Langone - Laura and Isaac Perlmutter Cancer Center /ID# 218077
  • Weill Cornell Medical Center /ID# 216911
  • University of Cincinnati Cancer Institute /ID# 216800
  • University Hospitals Cleveland /ID# 212241
  • The Ohio State University - The James /ID# 212298
  • Providence Cancer Center Oncology and Hematology Care - Westside Portland /ID# 215497
  • Allegheny General Hospital /ID# 214363
  • Prisma Health Cancer Institute - Faris /ID# 217946
  • Thompson Cancer Survival Ctr /ID# 217076
  • Houston Methodist Hospital - Scurlock Tower /ID# 215481
  • Utah Cancer Specialists /ID# 215496
  • Virginia Cancer Specialists /ID# 214328
  • Massey Cancer Centre /ID# 212527
  • Multicare Institute for Research and Innovation /ID# 217913
  • Northwest Medical Specialties /ID# 218484

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Dose Escalation Phase: Venetoclax + Pembrolizumab

Randomization Phase: Venetoclax + Pembrolizumab

Randomization Phase: Pembrolizumab Monotherapy

Arm Description

Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A.

Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A.

Participants will receive pembrolizumab Dose A

Outcomes

Primary Outcome Measures

Number of Participants with Dose-Limiting Toxicities (DLTs)
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)
Change in the SLD is assessed by exposure-response modeling

Secondary Outcome Measures

Maximum Plasma Concentration (Cmax) of Venetoclax
Maximum plasma concentration (Cmax) of venetoclax
Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
Time to maximum observed plasma concentration (Tmax) of venetoclax
Area Under the Plasma Concentration-Time Curve Over Time from 0 to 24 (AUC0-24) of Venetoclax in Plasma
Area Under the Plasma Concentration-time Curve (AUC) from 0-24 (AUC0-24)
Objective Response Rate (ORR)
ORR will be defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR).

Full Information

First Posted
February 17, 2020
Last Updated
February 10, 2021
Sponsor
AbbVie
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1. Study Identification

Unique Protocol Identification Number
NCT04274907
Brief Title
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

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
Company Decision
Study Start Date
June 30, 2020 (Actual)
Primary Completion Date
February 2, 2021 (Actual)
Study Completion Date
February 2, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer, Cancer
Keywords
Non Small Cell Lung Cancer (NSCLC), Cancer, Venetoclax, Pembrolizumab, PD-L1 Expression, ABT-199

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation Phase: Venetoclax + Pembrolizumab
Arm Type
Experimental
Arm Description
Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A.
Arm Title
Randomization Phase: Venetoclax + Pembrolizumab
Arm Type
Experimental
Arm Description
Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A.
Arm Title
Randomization Phase: Pembrolizumab Monotherapy
Arm Type
Active Comparator
Arm Description
Participants will receive pembrolizumab Dose A
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
Venclexta, ABT-199
Intervention Description
Tablet: Oral
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Intravenous (IV) Infusion
Primary Outcome Measure Information:
Title
Number of Participants with Dose-Limiting Toxicities (DLTs)
Description
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.
Time Frame
Up to 28 Days
Title
Change in the Sum of the Longest Diameter (SLD)
Description
Change in the SLD is assessed by exposure-response modeling
Time Frame
Up to 35 Cycles (Each Cycle is 21 Days)
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) of Venetoclax
Description
Maximum plasma concentration (Cmax) of venetoclax
Time Frame
Up to Cycle 1 (Each Cycle is 21 Days)
Title
Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
Description
Time to maximum observed plasma concentration (Tmax) of venetoclax
Time Frame
Up to Cycle 1 (Each Cycle is 21 Days)
Title
Area Under the Plasma Concentration-Time Curve Over Time from 0 to 24 (AUC0-24) of Venetoclax in Plasma
Description
Area Under the Plasma Concentration-time Curve (AUC) from 0-24 (AUC0-24)
Time Frame
Up to Cycle 1 (Each Cycle is 21 Days)
Title
Objective Response Rate (ORR)
Description
ORR will be defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR).
Time Frame
Up to 35 Cycles (Each Cycle is 21 Days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Univ of Alabama at Birmingham /ID# 214180
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Arizona Oncology Associates, PC-HOPE (Rudasill) /ID# 216984
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
St Jude Hospital dba St Joseph /ID# 212360
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95403
Country
United States
Facility Name
Icri /Id# 217071
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
AdventHealth Cancer Institute - Orlando /ID# 214444
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Georgia Regents University /ID# 217109
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Rush University Medical Center /ID# 212448
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago DCAM /ID# 214319
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1443
Country
United States
Facility Name
Ingalls Memorial Hosp /ID# 214952
City
Harvey
State/Province
Illinois
ZIP/Postal Code
60426
Country
United States
Facility Name
Fort Wayne Medical Oncology /ID# 214954
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46804
Country
United States
Facility Name
Ashland-Bellefonte Cancer Ctr /ID# 218511
City
Ashland
State/Province
Kentucky
ZIP/Postal Code
41101
Country
United States
Facility Name
University of Louisville /ID# 215195
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Central Maine Medical Center /ID# 216107
City
Lewiston
State/Province
Maine
ZIP/Postal Code
04240
Country
United States
Facility Name
Maryland Oncology Hematology /ID# 214131
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21044-3128
Country
United States
Facility Name
University of Massachusetts Ca /ID# 218744
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Karmanos Cancer Institute /ID# 216986
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Health System /ID# 216385
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Univ of Mississippi Med Ctr /ID# 216429
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216-4500
Country
United States
Facility Name
Washington University-School of Medicine /ID# 212355
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Methodist Estabrook Cancer Center /ID# 216910
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114-4108
Country
United States
Facility Name
University of Nebraska Medical Center /ID# 216754
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-6840
Country
United States
Facility Name
Hackensack Univ Med Ctr /ID# 216484
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Atlantic Health System /ID# 217067
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960-6136
Country
United States
Facility Name
Overlook Medical Center /ID# 219108
City
Summit
State/Province
New Jersey
ZIP/Postal Code
07901-3533
Country
United States
Facility Name
NYU Langone - Laura and Isaac Perlmutter Cancer Center /ID# 218077
City
New York
State/Province
New York
ZIP/Postal Code
10016-4744
Country
United States
Facility Name
Weill Cornell Medical Center /ID# 216911
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Cincinnati Cancer Institute /ID# 216800
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219-2364
Country
United States
Facility Name
University Hospitals Cleveland /ID# 212241
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
The Ohio State University - The James /ID# 212298
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210-1240
Country
United States
Facility Name
Providence Cancer Center Oncology and Hematology Care - Westside Portland /ID# 215497
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Allegheny General Hospital /ID# 214363
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Prisma Health Cancer Institute - Faris /ID# 217946
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605-4255
Country
United States
Facility Name
Thompson Cancer Survival Ctr /ID# 217076
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37916
Country
United States
Facility Name
Houston Methodist Hospital - Scurlock Tower /ID# 215481
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Utah Cancer Specialists /ID# 215496
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
Virginia Cancer Specialists /ID# 214328
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Massey Cancer Centre /ID# 212527
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Multicare Institute for Research and Innovation /ID# 217913
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Northwest Medical Specialties /ID# 218484
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.rxabbvie.com/
Description
This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Learn more about this trial

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

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