- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03829436
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
Status
Completed
Conditions
Intervention / Treatment
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
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California
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San Francisco, California, United States, 94158
- University of California - San Francisco
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Florida
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Miami, Florida, United States, 33176
- Miami Cancer Institute
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan Rogel Cancer Center
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New York
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New York, New York, United States, 10024
- Columbia University Medical Center
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North Carolina
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Huntersville, North Carolina, United States, 28078
- Carolina BioOncology Institute
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- Stephenson Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19107
- Thomas Jefferson University Hospital
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania Perelman School of Medicine
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Pittsburgh, Pennsylvania, United States, 15213
- UPMC Hillman Cancer Center
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Tennessee
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Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Institute - TN
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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:
- Subjects must not have experienced an irAE toxicity that led to permanent discontinuation of prior immunotherapy.
- 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: 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:
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Experimental: Part 3 TPST-1120
Selected dose of TPST-1120 administered orally twice daily until disease progression
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Selected dose of TPST-1120 administered orally twice daily until disease progression
Other Names:
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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:
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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
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Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
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From start of treatment to end of treatment, up to 36 months
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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.
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From start of treatment to end of treatment, up to 36 months
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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.
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From start of treatment to end of treatment, up to 36 months
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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)
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Maximum serum concentration (Cmax) of TPST-1120
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Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3 (cycle can be 21 or 28 days, depending on cohort assignment)
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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)
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Area under the curve (AUC) of TPST-1120
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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)
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Objective response rate
Time Frame: From start of treatment to end of treatment, up to 36 months
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Objective response rate per RECIST v1.1 criterion of TPST-1120 as a single agent and in combination with nivolumab.
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From start of treatment to end of treatment, up to 36 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Breast Diseases
- Head and Neck Neoplasms
- Kidney Neoplasms
- Carcinoma, Squamous Cell
- Breast Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Carcinoma, Renal Cell
- Carcinoma
- Squamous Cell Carcinoma of Head and Neck
- Cholangiocarcinoma
- Triple Negative Breast Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
Other Study ID Numbers
- TPST-1120-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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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