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

Phase 1

Terminated

• Conditions: Non Small Cell Lung Cancer; Cancer
• Interventions: Drug: Venetoclax; Drug: Pembrolizumab

• Registration Number: NCT04274907
• Lead Sponsor: AbbVie

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-17
• Study First Submitted QC: 2020-02-17
• Study First Posted: 2020-02-18
• Study Start: 2020-06-30
• Status Verified: 2021-02
• Primary Completion: 2021-02-02
• Study Completion: 2021-02-02
• Last Update Submitted: 2021-02-10
• Last Update Posted: 2021-02-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation Phase: Venetoclax + Pembrolizumab	Venetoclax	Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A.
Dose Escalation Phase: Venetoclax + Pembrolizumab	Pembrolizumab	Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A.
Randomization Phase: Venetoclax + Pembrolizumab	Venetoclax	Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A.
Randomization Phase: Pembrolizumab Monotherapy	Pembrolizumab	Participants will receive pembrolizumab Dose A
Randomization Phase: Venetoclax + Pembrolizumab	Pembrolizumab	Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A.

Primary Outcome Measures

Name	Time	Method
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.
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

Name	Time	Method
Maximum Plasma Concentration (Cmax) of Venetoclax	Up to Cycle 1 (Each Cycle is 21 Days)	Maximum plasma concentration (Cmax) of venetoclax
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
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)
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).

Trial Locations

Locations (39)

Univ of Alabama at Birmingham /ID# 214180; 🇺🇸 Birmingham, Alabama, United States

Arizona Oncology Associates, PC-HOPE (Rudasill) /ID# 216984; 🇺🇸 Tucson, Arizona, United States

St Jude Hospital dba St Joseph /ID# 212360; 🇺🇸 Santa Rosa, California, United States

Icri /Id# 217071; 🇺🇸 Whittier, California, United States

AdventHealth Cancer Institute - Orlando /ID# 214444; 🇺🇸 Orlando, Florida, United States

Georgia Regents University /ID# 217109; 🇺🇸 Augusta, Georgia, United States

Rush University Medical Center /ID# 212448; 🇺🇸 Chicago, Illinois, United States

University of Chicago DCAM /ID# 214319; 🇺🇸 Chicago, Illinois, United States

Ingalls Memorial Hosp /ID# 214952; 🇺🇸 Harvey, Illinois, United States

Fort Wayne Medical Oncology /ID# 214954; 🇺🇸 Fort Wayne, Indiana, United States

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