This is a phase 1/1b open label, multicenter dose escalation and dose expansion study to investigate the safety, tolerability and anti-tumor activity of TPST-1120, a small molecule selective antagonist of PPARα (peroxisome proliferator activated receptor alpha) as monotherapy and in combination with a systemic anticancer agent, nivolumab, an anti-PD1 antibody, in subjects with advanced solid tumors.
This is a phase 1/1b open label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of TPST-1120, a small molecule selective antagonist of PPARα (peroxisome proliferator activated receptor alpha) in adult subjects with selected advanced solid tumors. TPST-1120 will be administered as monotherapy and in combination with a systemic anticancer agent, nivolumab, an anti-PD1 antibody, in subjects with advanced solid tumors. This trial is composed of dose escalation and dose expansion cohorts.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
Subjects will receive escalating doses of TPST-1120 administered orally twice daily
Selected dose of TPST-1120 administered orally twice daily until disease progression
Selected dose of TPST-1120 administered orally twice daily in combination with nivolumab administered intravenously every 28 days until MTD is reached for TPST-1120 or until disease progression
University of California - San Francisco
San Francisco, California, United States
Miami Cancer Institute
Miami, Florida, United States
Johns Hopkins University
Baltimore, Maryland, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, United States
Columbia University Medical Center
New York, New York, United States
Carolina BioOncology Institute
Huntersville, North Carolina, United States
Stephenson Cancer Center
Oklahoma City, Oklahoma, United States
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
...and 1 more locations
Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
Time frame: From start of treatment to end of treatment, up to 36 months
Incidence of treatment-emergent adverse events as assessed by NCI-CTCAE v5.0 of TPST-1120 as a single agent and in combination with nivolumab.
Incidence of treatment-emergent adverse events as assessed by NCI-CTCAE v5.0 of TPST-1120 as a single agent and in combination with nivolumab.
Time frame: From start of treatment to end of treatment, up to 36 months
Identify the maximum tolerated dose
Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
Time frame: From start of treatment to end of treatment, up to 36 months
Assess pharmacokinetics: Maximum serum concentration (Cmax)
Maximum serum concentration (Cmax) of TPST-1120
Time frame: Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3 (cycle can be 21 or 28 days, depending on cohort assignment)
Assess pharmacokinetics: Area under the curve (AUC)
Area under the curve (AUC) of TPST-1120
Time frame: Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3, Day 1 of Cycles 5+ (cycle can be 21 or 28 days, depending on cohort assignment)
Objective response rate
Objective response rate per RECIST v1.1 criterion of TPST-1120 as a single agent and in combination with nivolumab.
Time frame: From start of treatment to end of treatment, up to 36 months
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