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 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 2 TPST-1120 + nivolumabExperimental + OpdivoPart 2 TPST-1120 + nivolumab
Part 3 TPST-1120ExperimentalPart 3 TPST-1120
Part 4 TPST-1120 + nivolumabExperimental + OpdivoPart 4 TPST-1120 + nivolumab

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 a systemic anticancer agent, nivolumab, an anti-PD1 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-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.
    

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 2 TPST-1120 + nivolumabExperimentalSubjects 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.
  • Part 2 TPST-1120 + nivolumab
Part 3 TPST-1120ExperimentalSelected dose of TPST-1120 administered orally twice daily until disease progression
  • Part 3 TPST-1120
Part 4 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 4 TPST-1120 + nivolumab

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

          -  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
      
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.
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.

Secondary Outcome Measures

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: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)
Safety Issue:
Description:Area under the curve (AUC) 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.

Details

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

Last Updated

August 6, 2021