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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

Sponsor
AbbVie (Industry)
Overall Status
Terminated
CT.gov ID
NCT04274907
Collaborator
(none)
2
Enrollment
39
Locations
3
Arms
7.1
Actual Duration (Months)
0.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
2 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 30, 2020
Actual Primary Completion Date :
Feb 2, 2021
Actual Study Completion Date :
Feb 2, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation Phase: Venetoclax + Pembrolizumab

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

Drug: Venetoclax
Tablet: Oral
Other Names:
  • Venclexta
  • ABT-199

    • Drug: Pembrolizumab
    Intravenous (IV) Infusion
    Other Names:
  • Keytruda

    		•
    Experimental: Randomization Phase: Venetoclax + Pembrolizumab

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

    Drug: Venetoclax
    Tablet: Oral
    Other Names:
  • Venclexta
  • ABT-199

    • Drug: Pembrolizumab
    Intravenous (IV) Infusion
    Other Names:
  • Keytruda

    		•
    Active Comparator: Randomization Phase: Pembrolizumab Monotherapy

    Participants will receive pembrolizumab Dose A

    Drug: Pembrolizumab
    Intravenous (IV) Infusion
    Other Names:
  • Keytruda

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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

    1. Maximum Plasma Concentration (Cmax) of Venetoclax [Up to Cycle 1 (Each Cycle is 21 Days)]

      Maximum plasma concentration (Cmax) of venetoclax

    2. 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

    3. 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)

    4. 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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Univ of Alabama at Birmingham /ID# 214180 Birmingham Alabama United States 35233
    2 Arizona Oncology Associates, PC-HOPE (Rudasill) /ID# 216984 Tucson Arizona United States 85704
    3 St Jude Hospital dba St Joseph /ID# 212360 Santa Rosa California United States 95403
    4 Icri /Id# 217071 Whittier California United States 90603
    5 AdventHealth Cancer Institute - Orlando /ID# 214444 Orlando Florida United States 32804
    6 Georgia Regents University /ID# 217109 Augusta Georgia United States 30912
    7 Rush University Medical Center /ID# 212448 Chicago Illinois United States 60612
    8 University of Chicago DCAM /ID# 214319 Chicago Illinois United States 60637-1443
    9 Ingalls Memorial Hosp /ID# 214952 Harvey Illinois United States 60426
    10 Fort Wayne Medical Oncology /ID# 214954 Fort Wayne Indiana United States 46804
    11 Ashland-Bellefonte Cancer Ctr /ID# 218511 Ashland Kentucky United States 41101
    12 University of Louisville /ID# 215195 Louisville Kentucky United States 40202
    13 Central Maine Medical Center /ID# 216107 Lewiston Maine United States 04240
    14 Maryland Oncology Hematology /ID# 214131 Columbia Maryland United States 21044-3128
    15 University of Massachusetts Ca /ID# 218744 Worcester Massachusetts United States 01655
    16 Karmanos Cancer Institute /ID# 216986 Detroit Michigan United States 48201
    17 Henry Ford Health System /ID# 216385 Detroit Michigan United States 48202
    18 Univ of Mississippi Med Ctr /ID# 216429 Jackson Mississippi United States 39216-4500
    19 Washington University-School of Medicine /ID# 212355 Saint Louis Missouri United States 63110
    20 Methodist Estabrook Cancer Center /ID# 216910 Omaha Nebraska United States 68114-4108
    21 University of Nebraska Medical Center /ID# 216754 Omaha Nebraska United States 68198-6840
    22 Hackensack Univ Med Ctr /ID# 216484 Hackensack New Jersey United States 07601
    23 Atlantic Health System /ID# 217067 Morristown New Jersey United States 07960-6136
    24 Overlook Medical Center /ID# 219108 Summit New Jersey United States 07901-3533
    25 NYU Langone - Laura and Isaac Perlmutter Cancer Center /ID# 218077 New York New York United States 10016-4744
    26 Weill Cornell Medical Center /ID# 216911 New York New York United States 10065
    27 University of Cincinnati Cancer Institute /ID# 216800 Cincinnati Ohio United States 45219-2364
    28 University Hospitals Cleveland /ID# 212241 Cleveland Ohio United States 44106
    29 The Ohio State University - The James /ID# 212298 Columbus Ohio United States 43210-1240
    30 Providence Cancer Center Oncology and Hematology Care - Westside Portland /ID# 215497 Portland Oregon United States 97225
    31 Allegheny General Hospital /ID# 214363 Pittsburgh Pennsylvania United States 15212
    32 Prisma Health Cancer Institute - Faris /ID# 217946 Greenville South Carolina United States 29605-4255
    33 Thompson Cancer Survival Ctr /ID# 217076 Knoxville Tennessee United States 37916
    34 Houston Methodist Hospital - Scurlock Tower /ID# 215481 Houston Texas United States 77030
    35 Utah Cancer Specialists /ID# 215496 Salt Lake City Utah United States 84106
    36 Virginia Cancer Specialists /ID# 214328 Fairfax Virginia United States 22031
    37 Massey Cancer Centre /ID# 212527 Richmond Virginia United States 23298
    38 Multicare Institute for Research and Innovation /ID# 217913 Tacoma Washington United States 98405
    39 Northwest Medical Specialties /ID# 218484 Tacoma Washington United States 98405

    Sponsors and Collaborators

    • AbbVie

    Investigators

    • Study Director: AbbVie Inc., AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT04274907
    Other Study ID Numbers:
    • M19-700
    First Posted:
    Feb 18, 2020
    Last Update Posted:
    Feb 11, 2021
    Last Verified:
    Feb 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by AbbVie
    Non Small Cell Lung Cancer (NSCLC)
    Cancer
    Venetoclax
    Pembrolizumab
    PD-L1 Expression
    ABT-199
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Pembrolizumab
    Venetoclax

    Study Results

    No Results Posted as of Feb 11, 2021