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

June 28, 2023 updated by: Tempest Therapeutics

A Phase 1/1b Open-label, Dose-escalation and Dose-expansion Study of TPST-1120 as a Single Agent or in Combination With Systemic Anti-Cancer Therapies in Subjects With Advanced Solid Tumors

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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 1

Contacts and Locations

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

Study Locations

    • California
      • San Francisco, California, United States, 94158
        • University of California - San Francisco
    • Florida
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Rogel Cancer Center
    • New York
      • New York, New York, United States, 10024
        • Columbia University Medical Center
    • North Carolina
      • Huntersville, North Carolina, United States, 28078
        • Carolina BioOncology Institute
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Stephenson Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Perelman School of Medicine
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Hillman Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute - TN

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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:

    1. Subjects must not have experienced an irAE toxicity that led to permanent discontinuation of prior immunotherapy.
    2. Any unresolved irAE > Grade 1 with prior immunotherapy treatment.
  • Symptomatic, untreated or actively progressing central nervous system metastases
  • Have received fibrates within 28 days before first dose of investigational agent

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

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
Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
Other Names:
  • Experimental
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.
Subjects will receive escalating doses of TPST-1120 administered orally twice daily
Other Names:
  • Experimental + Opdivo
Experimental: Part 3 TPST-1120
Selected dose of TPST-1120 administered orally twice daily until disease progression
Selected dose of TPST-1120 administered orally twice daily until disease progression
Other Names:
  • Experimental
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
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
Other Names:
  • Experimental + Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 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.
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.
From start of treatment to end of treatment, up to 36 months
Identify the maximum tolerated dose
Time Frame: 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.
From start of treatment to end of treatment, up to 36 months

Secondary Outcome Measures

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

Collaborators and Investigators

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

Investigators

  • Study Director: Robert Stagg, PharmD, Tempest Therapeutics

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 Major Dates

Study Start (Actual)

March 20, 2019

Primary Completion (Actual)

September 7, 2022

Study Completion (Actual)

September 7, 2022

Study Registration Dates

First Submitted

January 30, 2019

First Submitted That Met QC Criteria

February 1, 2019

First Posted (Actual)

February 4, 2019

Study Record Updates

Last Update Posted (Actual)

July 3, 2023

Last Update Submitted That Met QC Criteria

June 28, 2023

Last Verified

June 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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