This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03829436
Recruitment Status : Completed
First Posted : February 4, 2019
Last Update Posted : July 3, 2023
Sponsor:
Information provided by (Responsible Party):
Tempest Therapeutics

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
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 Phase 1

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 20, 2019
Actual Primary Completion Date : September 7, 2022
Actual Study Completion Date : September 7, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Other Name: 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.
 Drug: Part 2 TPST-1120 + nivolumab
Subjects will receive escalating doses of TPST-1120 administered orally twice daily
Other Name: Experimental + Opdivo
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
Other Name: 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
 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
Other Name: Experimental + Opdivo


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03829436


Locations
Layout table for location information
United States, California
University of California - San Francisco
San Francisco, California, United States, 94158
United States, Florida
Miami Cancer Institute
Miami, Florida, United States, 33176
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Michigan
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, New York
Columbia University Medical Center
New York, New York, United States, 10024
United States, North Carolina
Carolina BioOncology Institute
Huntersville, North Carolina, United States, 28078
United States, Oklahoma
Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Sarah Cannon Research Institute - TN
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Tempest Therapeutics
Investigators
Layout table for investigator information
Study Director: Robert Stagg, PharmD Tempest Therapeutics
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Tempest Therapeutics
ClinicalTrials.gov Identifier: NCT03829436    
Other Study ID Numbers: TPST-1120-001
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: July 3, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Renal Cell
Triple Negative Breast Neoplasms
Cholangiocarcinoma
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urogenital Diseases
Male Urogenital Diseases
Carcinoma, Squamous Cell
Adenocarcinoma
Kidney Neoplasms
 Urologic Neoplasms
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Kidney Diseases
Urologic Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Head and Neck Neoplasms
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action