PBF-1129 and Nivolumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT05234307|
Recruitment Status : Not yet recruiting
First Posted : February 10, 2022
Last Update Posted : February 10, 2022
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Lung Non-Small Cell Carcinoma Recurrent Lung Non-Small Cell Carcinoma Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8||Drug: Adenosine A2B Receptor Antagonist PBF-1129 Procedure: Biospecimen Collection Biological: Nivolumab||Phase 1|
I. To determine the safety and tolerability of the combination of adenosine A2B receptor antagonist PBF-1129 (PBF-1129) and nivolumab in patients with advanced non-small cell lung cancer (NSCLC) based upon the Common Terminology Criteria for Adverse Events (CTCAE) version 5 criteria.
I. To determine the efficacy of the combination of PBF-1129 and nivolumab in patients with advanced NSCLC, including progression-free survival (PFS), objective response (ORR), disease control rate (DCR), and overall survival (OS) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
I. To study the effect of PBF-1129 on the levels of myeloid-derived suppressor cells (MDSC) within the tumor microenvironment (TME) and in peripheral blood of study patients.
II. To evaluate correlative biomarkers that might predict disease response to treatment with PBF-1129 and nivolumab therapy in previously treated NSCLC patients including STK11 genetic alterations and a transcriptional signature of LKB1 functional status developed by the Carbone lab.
OUTLINE: This is a dose-escalation study of PBF-1129 given in combination with immune checkpoint blockade.
Patients receive adenosine A2B receptor antagonist PBF-1129 (PBF-1129) orally (PO) once daily (QD) and nivolumab intravenously (IV) on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for up to 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib Trial of PBF-1129 and Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer|
|Estimated Study Start Date :||April 30, 2022|
|Estimated Primary Completion Date :||December 31, 2024|
|Estimated Study Completion Date :||December 31, 2025|
Experimental: Treatment (PBF-1129, nivolumab)
Patients receive PBF-1129 PO QD and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Adenosine A2B Receptor Antagonist PBF-1129
Procedure: Biospecimen Collection
- Incidence of adverse events [ Time Frame: Up to 30 days after the last dose of study treatment ]Safety will be measured by the occurrence of dose-limited toxicities as well as any other adverse events as defined in Common Terminology Criteria for Adverse Events version 5. Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. All patients who have received at least one dose of the therapeutic agents will be evaluable for toxicity and tolerability.
- Overall objective response rate [ Time Frame: Up to 1 year after treatment discontinuation ]Will be calculated and exact binomial 95% confidence interval (CI) will be provided.
- Disease control rate [ Time Frame: Up to 1 year after treatment discontinuation ]Will be calculated and exact binomial 95% CI will be provided.
- Overall survival [ Time Frame: Up to 1 year after treatment discontinuation ]Will be defined as time from initiation of therapy to death, or censored at last follow-up date if the subject is alive. Kaplan-Meier methods will be used to estimate overall survival with 95% CI.
- Progression free survival [ Time Frame: Up to 1 year after treatment discontinuation ]Will be defined as the time from initiation of therapy to the time of Response Evaluation Criteria in Solid Tumors progression or death. Kaplan-Meier methods will be used to estimate progression free survival with 95% CI.
- Levels of myeloidderived suppressor cells (MDSC) [ Time Frame: Up to 1 year after treatment discontinuation ]Baseline MDSC and the changes upon treatment will be compared between responders and non-responders using two sample t-test or non-parametric Wilcoxon test as appropriate. Linear mixed effect models will be used to evaluate MDSC levels over the time with the response, as well as the clinical outcomes including resistance to treatment. Potential confounders (patients' demographics and clinical characteristics) might be included in the models.
- Correlative biomarkers [ Time Frame: Up to 1 year after treatment discontinuation ]We will compare responses within this cohort. The impact of STK11/LKB1 alterations and how it is associated with response will be assessed using logistic regression analyses.
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): NCT05234307
|Contact: The Ohio State University Comprehensive Cancer Center||800-293-5066||OSUCCCClinicaltrials@osumc.edu|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|Contact: Dwight H. Owen, MD, MS, FACP 614-293-6786 firstname.lastname@example.org|
|Principal Investigator: Dwight H. Owen, MD, MS, FACP|
|Principal Investigator:||Dwight H Owen||Ohio State University Comprehensive Cancer Center|