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

A Phase 1b Study of Venetoclax in Combination With Pembrolizumab in Subjects With Previously Untreated NSCLC Whose Tumors Have High PD-L1 Expression

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.

Study Overview

• Status: Terminated
• Conditions: Cancer; Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Venetoclax; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 28 Days
Change in the Sum of the Longest Diameter (SLD)	Change in the SLD is assessed by exposure-response modeling	Up to 35 Cycles (Each Cycle is 21 Days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Venetoclax	Maximum plasma concentration (Cmax) of venetoclax	Up to Cycle 1 (Each Cycle is 21 Days)
Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax	Time to maximum observed plasma concentration (Tmax) of venetoclax	Up to Cycle 1 (Each Cycle is 21 Days)
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)	Up to Cycle 1 (Each Cycle is 21 Days)
Objective Response Rate (ORR)	ORR will be defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR).	Up to 35 Cycles (Each Cycle is 21 Days)

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Actual): February 2, 2021
• Study Completion (Actual): February 2, 2021

Study Registration Dates

• First Submitted: February 17, 2020
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (Actual): February 18, 2020

Study Record Updates

• Last Update Posted (Actual): February 11, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Cancer; Pembrolizumab; Venetoclax; ABT-199; Non Small Cell Lung Cancer (NSCLC); PD-L1 Expression
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Venetoclax; Pembrolizumab
• Other Study ID Numbers: M19-700

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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