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
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| ClinicalTrials.gov Identifier: NCT04274907 |
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Recruitment Status :
Terminated
(Company Decision)
First Posted : February 18, 2020
Last Update Posted : February 11, 2021
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non Small Cell Lung Cancer Cancer | Drug: Venetoclax Drug: Pembrolizumab | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 2 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | June 30, 2020 |
| Actual Primary Completion Date : | February 2, 2021 |
| Actual Study Completion Date : | February 2, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation Phase: Venetoclax + Pembrolizumab
Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A.
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Drug: Venetoclax
Tablet: Oral
Other Names:
Drug: Pembrolizumab Intravenous (IV) Infusion
Other Name: Keytruda |
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Experimental: Randomization Phase: Venetoclax + Pembrolizumab
Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A.
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Drug: Venetoclax
Tablet: Oral
Other Names:
Drug: Pembrolizumab Intravenous (IV) Infusion
Other Name: Keytruda |
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Active Comparator: Randomization Phase: Pembrolizumab Monotherapy
Participants will receive pembrolizumab Dose A
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Drug: Pembrolizumab
Intravenous (IV) Infusion
Other Name: Keytruda |
- 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
- 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).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04274907
Show 39 study locations
| Study Director: | AbbVie Inc. | AbbVie |
| Responsible Party: | AbbVie |
| ClinicalTrials.gov Identifier: | NCT04274907 |
| Other Study ID Numbers: |
M19-700 |
| First Posted: | February 18, 2020 Key Record Dates |
| Last Update Posted: | February 11, 2021 |
| Last Verified: | February 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| 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 |
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Non Small Cell Lung Cancer (NSCLC) Cancer Venetoclax |
Pembrolizumab PD-L1 Expression ABT-199 |
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases |
Carcinoma, Bronchogenic Bronchial Neoplasms Pembrolizumab Venetoclax Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |