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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04274907
• Other study ID #: M19-700
• Status: Terminated
• Phase: Phase 1
• Start date: June 30, 2020
• Est. completion date: February 2, 2021

Study information

• Verified date: February 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 2, 2021
• Est. primary completion date: February 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• Venetoclax
Tablet: Oral
• Pembrolizumab
Intravenous (IV) Infusion

Locations

Country	Name	City	State
United States	Ashland-Bellefonte Cancer Ctr /ID# 218511	Ashland	Kentucky
United States	Georgia Regents University /ID# 217109	Augusta	Georgia
United States	Univ of Alabama at Birmingham /ID# 214180	Birmingham	Alabama
United States	Rush University Medical Center /ID# 212448	Chicago	Illinois
United States	University of Chicago DCAM /ID# 214319	Chicago	Illinois
United States	University of Cincinnati Cancer Institute /ID# 216800	Cincinnati	Ohio
United States	University Hospitals Cleveland /ID# 212241	Cleveland	Ohio
United States	Maryland Oncology Hematology /ID# 214131	Columbia	Maryland
United States	The Ohio State University - The James /ID# 212298	Columbus	Ohio
United States	Henry Ford Health System /ID# 216385	Detroit	Michigan
United States	Karmanos Cancer Institute /ID# 216986	Detroit	Michigan
United States	Virginia Cancer Specialists /ID# 214328	Fairfax	Virginia
United States	Fort Wayne Medical Oncology /ID# 214954	Fort Wayne	Indiana
United States	Prisma Health Cancer Institute - Faris /ID# 217946	Greenville	South Carolina
United States	Hackensack Univ Med Ctr /ID# 216484	Hackensack	New Jersey
United States	Ingalls Memorial Hosp /ID# 214952	Harvey	Illinois
United States	Houston Methodist Hospital - Scurlock Tower /ID# 215481	Houston	Texas
United States	Univ of Mississippi Med Ctr /ID# 216429	Jackson	Mississippi
United States	Thompson Cancer Survival Ctr /ID# 217076	Knoxville	Tennessee
United States	Central Maine Medical Center /ID# 216107	Lewiston	Maine
United States	University of Louisville /ID# 215195	Louisville	Kentucky
United States	Atlantic Health System /ID# 217067	Morristown	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	Methodist Estabrook Cancer Center /ID# 216910	Omaha	Nebraska
United States	University of Nebraska Medical Center /ID# 216754	Omaha	Nebraska
United States	AdventHealth Cancer Institute - Orlando /ID# 214444	Orlando	Florida
United States	Allegheny General Hospital /ID# 214363	Pittsburgh	Pennsylvania
United States	Providence Cancer Center Oncology and Hematology Care - Westside Portland /ID# 215497	Portland	Oregon
United States	Massey Cancer Centre /ID# 212527	Richmond	Virginia
United States	Washington University-School of Medicine /ID# 212355	Saint Louis	Missouri
United States	Utah Cancer Specialists /ID# 215496	Salt Lake City	Utah
United States	St Jude Hospital dba St Joseph /ID# 212360	Santa Rosa	California
United States	Overlook Medical Center /ID# 219108	Summit	New Jersey
United States	Multicare Institute for Research and Innovation /ID# 217913	Tacoma	Washington
United States	Northwest Medical Specialties /ID# 218484	Tacoma	Washington
United States	Arizona Oncology Associates, PC-HOPE (Rudasill) /ID# 216984	Tucson	Arizona
United States	Icri /Id# 217071	Whittier	California
United States	University of Massachusetts Ca /ID# 218744	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Maximum Plasma Concentration (Cmax) of Venetoclax	Maximum plasma concentration (Cmax) of venetoclax	Up to Cycle 1 (Each Cycle is 21 Days)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

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