TPST-1120 as Monotherapy and in Combination With Nivolumab in Subjects With Advanced Cancers

Phase 1

Completed

• Conditions: Metastatic Castration Resistant Prostate Cancer; Non-small Cell Lung Cancer; Triple-Negative Breast Cancer; Pancreatic Cancer; Colorectal Cancer; Squamous Cell Carcinoma of Head and Neck; Cholangiocarcinoma; Hepatocellular Carcinoma; Urothelial Carcinoma; GastroEsophageal Cancer
• Interventions: Drug: Part 1 TPST-1120; Drug: Part 2 TPST-1120 + nivolumab; Drug: Part 3 TPST-1120; Drug: Part 4 TPST-1120 + nivolumab

• Registration Number: NCT03829436
• Lead Sponsor: Tempest Therapeutics

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2019-01-30
• Study First Submitted QC: 2019-02-01
• Study First Posted: 2019-02-04
• Study Start: 2019-03-20
• Primary Completion: 2022-09-07
• Study Completion: 2022-09-07
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-28
• Last Update Posted: 2023-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1 TPST-1120	Part 1 TPST-1120	Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
Part 2 TPST-1120 + nivolumab	Part 2 TPST-1120 + nivolumab	Subjects will receive escalating doses 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.
Part 3 TPST-1120	Part 3 TPST-1120	Selected dose of TPST-1120 administered orally twice daily until disease progression
Part 4 TPST-1120 + nivolumab	Part 4 TPST-1120 + nivolumab	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

Primary Outcome Measures

Name	Time	Method
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.	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 dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.	From start of treatment to end of treatment, up to 36 months	Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
Identify the maximum tolerated dose	From start of treatment to end of treatment, up to 36 months	Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.

Secondary Outcome Measures

Name	Time	Method
Assess pharmacokinetics: Maximum serum concentration (Cmax)	Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3 (cycle can be 21 or 28 days, depending on cohort assignment)	Maximum serum concentration (Cmax) of TPST-1120
Objective response rate	From start of treatment to end of treatment, up to 36 months	Objective response rate per RECIST v1.1 criterion of TPST-1120 as a single agent and in combination with nivolumab.
Assess pharmacokinetics: Area under the curve (AUC)	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)	Area under the curve (AUC) of TPST-1120

Trial Locations

Locations (11)

University of Michigan Rogel Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

Miami Cancer Institute; 🇺🇸 Miami, Florida, United States

University of California - San Francisco; 🇺🇸 San Francisco, California, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pennsylvania Perelman School of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Carolina BioOncology Institute; 🇺🇸 Huntersville, North Carolina, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Sarah Cannon Research Institute - TN; 🇺🇸 Nashville, Tennessee, United States