Clinical Trials /

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

NCT03829436

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: TPST-1120-001
  • NCT ID: NCT03829436

Conditions

  • 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

Interventions

DrugSynonymsArms
Part 1 TPST-1120ExperimentalPart 1 TPST-1120
Part 2a TPST-1120 + nivolumabExperimental + OpdivoPart 2a TPST-1120 + nivolumab
Part 2b TPST-1120 + docetaxelExperimental + TaxoterePart 2b TPST-1120 + docetaxel
Part 2c TPST-1120 + cetuximabExperimental + ErbituxPart 2c TPST-1120 + cetuximab
Part 3 TPST-1120ExperimentalPart 3 TPST-1120
Part 4a TPST-1120 + nivolumabExperimental + OpdivoPart 4a TPST-1120 + nivolumab
Part 4b TPST-1120 + docetaxelExperimental + TaxoterePart 4b TPST-1120 + docetaxel
Part 4c TPST-1120 + cetuximabExperimental + ErbituxPart 4c TPST-1120 + cetuximab

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1 TPST-1120ExperimentalSubjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
  • Part 1 TPST-1120
Part 2a TPST-1120 + nivolumabExperimentalSubjects will receive escalating doses of TPST-1120 administered orally twice daily
  • Part 2a TPST-1120 + nivolumab
Part 2b TPST-1120 + docetaxelExperimentalSubjects 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
  • Part 2b TPST-1120 + docetaxel
Part 2c TPST-1120 + cetuximabExperimentalSubjects 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
  • Part 2c TPST-1120 + cetuximab
Part 3 TPST-1120ExperimentalSelected dose of TPST-1120 administered orally twice daily until disease progression
  • Part 3 TPST-1120
Part 4a TPST-1120 + nivolumabExperimentalSelected 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
  • Part 4a TPST-1120 + nivolumab
Part 4b TPST-1120 + docetaxelExperimentalSelected 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
  • Part 4b TPST-1120 + docetaxel
Part 4c TPST-1120 + cetuximabExperimentalSelected 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
  • Part 4c TPST-1120 + cetuximab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure: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)
Safety Issue:
Description:Area under the curve (AUC) of TPST-1120
Measure: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)
Safety Issue:
Description:Maximum serum concentration (Cmax) of TPST-1120
Measure:Objective response rate
Time Frame:From start of treatment to end of treatment, up to 36 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tempest Therapeutics

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