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 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.
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
Drug | Synonyms | Arms |
---|
Venetoclax | Venclexta, ABT-199 | Dose Escalation Phase: Venetoclax + Pembrolizumab |
Pembrolizumab | Keytruda | Dose 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 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Escalation Phase: Venetoclax + Pembrolizumab | Experimental | Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A. | |
Randomization Phase: Venetoclax + Pembrolizumab | Experimental | Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A. | |
Randomization Phase: Pembrolizumab Monotherapy | Active Comparator | Participants will receive pembrolizumab Dose A | |
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.
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: | Terminated |
Lead Sponsor: | AbbVie |
Trial Keywords
- Non Small Cell Lung Cancer (NSCLC)
- Cancer
- Venetoclax
- Pembrolizumab
- PD-L1 Expression
- ABT-199
Last Updated
February 11, 2021