Cancer, Non Small Cell Lung Cancer
Conditions
Keywords
Non Small Cell Lung Cancer (NSCLC), Cancer, Venetoclax, Pembrolizumab, PD-L1 Expression, ABT-199
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.
Interventions
DRUGVenetoclax
Tablet: Oral
DRUGPembrolizumab
Intravenous (IV) Infusion
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Outcome results
None listed