TPST-1120 As Monotherapy And In Combination With Nivolumab In Subjects With Advanced Cancers

Study Overview

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

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.

Hepatocellular Carcinoma
Metastatic Castration Resistant Prostate Cancer
Renal Cell Carcinoma
Non-small Cell Lung Cancer
Colorectal Cancer
Squamous Cell Carcinoma of Head and Neck
Triple-Negative Breast Cancer
Urothelial Carcinoma
Cholangiocarcinoma
GastroEsophageal Cancer
Pancreatic Cancer
Sarcoma

DRUG: Part 1 TPST-1120
DRUG: Part 2 TPST-1120 + nivolumab
DRUG: Part 3 TPST-1120
DRUG: Part 4 TPST-1120 + nivolumab

TPST-1120-001

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-01-30	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-06-28
First Submitted that Met QC Criteria 2019-02-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-07-03
First Posted (ACTUAL) 2019-02-04	Results First Posted N/A	Last Verified 2023-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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	DRUG: 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
EXPERIMENTAL: 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.	DRUG: Part 2 TPST-1120 + nivolumab Subjects will receive escalating doses of TPST-1120 administered orally twice daily
EXPERIMENTAL: Part 3 TPST-1120 Selected dose of TPST-1120 administered orally twice daily until disease progression	DRUG: Part 3 TPST-1120 Selected dose of TPST-1120 administered orally twice daily until disease progression
EXPERIMENTAL: 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	DRUG: 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	Measure Description	Time Frame
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.	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.	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.	From start of treatment to end of treatment, up to 36 months

Secondary Outcome Measures	Measure Description	Time Frame
Assess pharmacokinetics: Maximum serum concentration (Cmax)	Maximum serum concentration (Cmax) of TPST-1120	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	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.	From start of treatment to end of treatment, up to 36 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Eastern Cooperative Oncology Group performance status of 0-1 at enrollment
Progressive disease or previously untreated tumors for which no standard therapy exists or treatment naïve at the time of study entry are eligible
Have at least one measurable lesion according to RECIST v1.1
Subjects with the following histologies are eligible and who are refractory to, have failed, are intolerant to, are ineligible for standard therapy, or for which no standard therapy exists are eligible: Part 1 (Dose Escalation- Monotherapy): RCC, NSCLC, CRC, metastatic castration resistant prostate cancer (mCRPC), cholangiocarcinoma, TNBC, pancreatic cancer, HCC, gastroesophageal cancer, squamous cell carcinoma of head and neck (SCCHN), urothelial bladder cancer (UBC), and sarcoma (liposarcomas and leiomyosarcomas); Part 2 (Dose Escalation-Combination with nivolumab): RCC, HCC, and cholangiocarcinoma; Part 3 (Dose Expansion-Monotherapy): RCC, HCC and cholangiocarcinoma; Part 4 (Dose Expansion-Combination with nivolumab): HCC.

Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, a specimen-collection study or the follow-up period of an interventional study
Any chemotherapy, monoclonal antibody therapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment within 28 days of commencing TPST-1120 treatment. Targeted therapy such as tyrosine kinase inhibitors within 14 days of commencing first dose of study drug(s)
For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA4 therapy:

Symptomatic, untreated or actively progressing central nervous system metastases
Have received fibrates within 28 days before first dose of investigational agent

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Robert Stagg, PharmD, Tempest Therapeutics

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record