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

• ClinicalTrials.gov Identifier: NCT04274907
• Recruitment Status: Terminated
• First Posted: February 18, 2020
• Last Update Posted: February 11, 2021
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: February 17, 2020
• First Posted Date: February 18, 2020
• Last Update Posted Date: February 11, 2021
• Actual Study Start Date: June 30, 2020
• Actual Primary Completion Date: February 2, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2020)

• Number of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: 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) [ Time Frame: Up to 35 Cycles (Each Cycle is 21 Days) ]
  Change in the SLD is assessed by exposure-response modeling

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 17, 2020)

• Maximum Plasma Concentration (Cmax) of Venetoclax [ Time Frame: Up to Cycle 1 (Each Cycle is 21 Days) ]
  Maximum plasma concentration (Cmax) of venetoclax
• Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non Small Cell Lung Cancer
• Cancer

Intervention

• Drug: Venetoclax
  Tablet: Oral
  Other Names:

  • Venclexta
  • ABT-199
• Drug: Pembrolizumab
  Intravenous (IV) Infusion
  Other Name: Keytruda

Study Arms

• Experimental: Dose Escalation Phase: Venetoclax + Pembrolizumab
  Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A.
  Interventions:

  • Drug: Venetoclax
  • Drug: Pembrolizumab
• Experimental: Randomization Phase: Venetoclax + Pembrolizumab
  Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A.
  Interventions:

  • Drug: Venetoclax
  • Drug: Pembrolizumab
• Active Comparator: Randomization Phase: Pembrolizumab Monotherapy
  Participants will receive pembrolizumab Dose A
  Intervention: Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 10, 2021): 2
• Original Estimated Enrollment (submitted: February 17, 2020): 100
• Actual Study Completion Date: February 2, 2021
• Actual Primary Completion Date: February 2, 2021 (Final data collection date for primary outcome measure)

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.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04274907
• Other Study ID Numbers: M19-700
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: February 2021