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TPST-1120 as Monotherapy and in Combination With (Nivolumab, Docetaxel or Cetuximab) in Subjects With Advanced Cancers

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ClinicalTrials.gov Identifier: NCT03829436
Recruitment Status : Not yet recruiting
First Posted : February 4, 2019
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
Tempest Therapeutics

Study Description
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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 other systemic anticancer agents including nivolumab, an anti-PD1 antibody, docetaxel, a cytotoxic chemotherapeutic agent and cetuximab, an anti-EGFR 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 2a TPST-1120 + nivolumab Drug: Part 2b TPST-1120 + docetaxel Drug: Part 2c TPST-1120 + cetuximab Drug: Part 3 TPST-1120 Drug: Part 4a TPST-1120 + nivolumab Drug: Part 4b TPST-1120 + docetaxel Drug: Part 4c TPST-1120 + cetuximab 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 will be administered as monotherapy and in combination with standard of care systemic anticancer agents including nivolumab, an anti-PD1 antibody, docetaxel, a cytotoxic chemotherapeutic agent and cetuximab, an anti-EGFR antibody in subjects with advanced solid tumors. This trial is composed of dose escalation and dose expansion cohorts.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 338 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
Estimated Study Start Date : March 11, 2019
Estimated Primary Completion Date : February 18, 2022
Estimated Study Completion Date : June 23, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 2a TPST-1120 + nivolumab
Subjects will receive escalating doses of TPST-1120 administered orally twice daily
 Drug: Part 2a TPST-1120 + nivolumab
Subjects will receive escalating doses of TPST-1120 administered orally twice daily
Other Name: Experimental + Opdivo
Experimental: Part 2b TPST-1120 + docetaxel
Subjects will receive escalating doses of TPST-1120 administered orally twice daily in combination with docetaxel administered intravenously every 21 days until MTD is reached for TPST-1120 or until disease progression
 Drug: Part 2b TPST-1120 + docetaxel
Subjects will receive escalating doses of TPST-1120 administered orally twice daily in combination with docetaxel administered intravenously every 21 days until MTD is reached for TPST-1120 or until disease progression
Other Name: Experimental + Taxotere
Experimental: Part 2c TPST-1120 + cetuximab
Subjects will receive escalating doses of TPST-1120 administered orally twice daily in combination with cetuximab administered intravenously every 7 days until MTD is reached for TPST-1120 or until disease progression
 Drug: Part 2c TPST-1120 + cetuximab
Subjects will receive escalating doses of TPST-1120 administered orally twice daily in combination with cetuximab administered intravenously every 7 days until MTD is reached for TSPT-1120 or until disease progression
Other Name: Experimental + Erbitux
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 4a 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 4a 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 TSPT-1120 or until disease progression
Other Name: Experimental + Opdivo
Experimental: Part 4b TPST-1120 + docetaxel
Selected dose of TPST-1120 administered orally twice daily in combination with docetaxel administered intravenously every 21 days until MTD is reached for TPST-1120 or until disease progression
 Drug: Part 4b TPST-1120 + docetaxel
Selected dose of TPST-1120 administered orally twice daily in combination with docetaxel administered intravenously every 21 days until MTD is reached for TPST-1120 or until disease progression
Other Name: Experimental + Taxotere
Experimental: Part 4c TPST-1120 + cetuximab
Selected dose of TPST-1120 administered orally twice daily in combination with cetuximab administered intravenously every 7 days until MTD is reached for TPST-1120 or until disease progression
 Drug: Part 4c TPST-1120 + cetuximab
Selected dose of TPST-1120 administered orally twice daily in combination with cetuximab administered intravenously every 7 days until MTD is reached for TPST-1120 or until disease progression
Other Name: Experimental + Erbitux


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab, in combination with docetaxel and in combination with cetuximab. [ 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, in combination with docetaxel and in combination with cetuximab.

  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, in combination with docetaxel and in combination with cetuximab. [ 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, in combination with docetaxel and in combination with cetuximab.

  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, in combination with docetaxel and in combination with cetuximab.


Secondary Outcome Measures :
  1. Assess pharmacokinetics: Area under the curve (AUC) [ 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) ]
    Area under the curve (AUC) of TSPT-1120

  2. 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

  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, in combination with docetaxel and in combination with cetuximab.


Eligibility Criteria
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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
  • Must be willing to consent and undergo tumor biopsies

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)
  • Any unresolved immune related adverse event > 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
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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


Contacts
Contact: Matthew Hauffe (415) 354-5571 ext 116 mhauffe@tempesttx.com
Contact: Elia Borbas, RN, BSN (415) 696-7640 ext 115 eborbas@tempesttx.com

Sponsors and Collaborators
Tempest Therapeutics
Investigators
Study Director: Ginna Laport, MD Tempest Therapeutics
More Information
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Responsible Party: Tempest Therapeutics
ClinicalTrials.gov Identifier: NCT03829436     History of Changes
Other Study ID Numbers: TPST-1120-001
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Colorectal Neoplasms
Pancreatic Neoplasms
Prostatic Neoplasms
Triple Negative Breast Neoplasms
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Intestinal Neoplasms
Gastrointestinal Neoplasms
 Digestive System Neoplasms
Neoplasms, Squamous Cell
Endocrine Gland Neoplasms
Pancreatic Diseases
Liver Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Genital Neoplasms, Male
Breast Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Carcinoma, Hepatocellular
Carcinoma, Renal Cell