Clinical Trials /

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

NCT04274907

Description:

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 will 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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: M19-700
  • NCT ID: NCT04274907

Conditions

  • Non Small Cell Lung Cancer
  • Cancer

Interventions

DrugSynonymsArms
VenetoclaxVenclexta, ABT-199Dose Escalation Phase: Venetoclax + Pembrolizumab
PembrolizumabKeytrudaDose Escalation Phase: Venetoclax + Pembrolizumab

Purpose

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 will 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.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Phase: Venetoclax + PembrolizumabExperimentalParticipants will receive escalating doses of venetoclax in combination with pembrolizumab dose A
  • Venetoclax
  • Pembrolizumab
Randomization Phase: Venetoclax + PembrolizumabExperimentalParticipants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab dose A
  • Venetoclax
  • Pembrolizumab
Randomization Phase: Pembrolizumab MonotherapyActive ComparatorParticipants will receive pembrolizumab dose A
  • Pembrolizumab

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 and during treatment.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose-Limiting Toxicities (DLTs)
Time Frame:Up to 28 Days
Safety Issue:
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.

Secondary Outcome Measures

Measure:Maximum Plasma Concentration (Cmax) of Venetoclax
Time Frame:Up to Cycle 1 (Each Cycle is 21 Days)
Safety Issue:
Description:Maximum plasma concentration (Cmax) of venetoclax
Measure:Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
Time Frame:Up to Cycle 1 (Each Cycle is 21 Days)
Safety Issue:
Description:Time to maximum observed plasma concentration (Tmax) of venetoclax
Measure:Area Under the Plasma Concentration-Time Curve Over Time from 0 to 24 (AUC0-24) of Venetoclax in Plasma
Time Frame:Up to Cycle 1 (Each Cycle is 21 Days)
Safety Issue:
Description:Area Under the Plasma Concentration-time Curve (AUC) from 0-24 (AUC0-24)
Measure:Objective Response Rate (ORR)
Time Frame:Up to 35 Cycles (Each Cycle is 21 Days)
Safety Issue:
Description:ORR will be defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Non Small Cell Lung Cancer (NSCLC)
  • Cancer
  • Venetoclax
  • Pembrolizumab
  • PD-L1 Expression
  • ABT-199

Last Updated

February 17, 2020