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

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ClinicalTrials.gov Identifier: NCT03829436
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : August 6, 2021
Sponsor:
Information provided by (Responsible Party):
Tempest Therapeutics

Tracking Information
First Submitted Date  ICMJE January 30, 2019
First Posted Date  ICMJE February 4, 2019
Last Update Posted Date August 6, 2021
Actual Study Start Date  ICMJE March 20, 2019
Estimated Primary Completion Date February 18, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2020)
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • 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.
  • Incidence of treatment-emergent adverse events as assessed by NCI-CTCAE v5.0 of TSPT-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 TSPT-1120 as a single agent and in combination with nivolumab, in combination with docetaxel and in combination with cetuximab.
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2020)
  • 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
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • 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
  • 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 TSPT-1120
  • 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 TSPT-1120 as a single agent and in combination with nivolumab, in combination with docetaxel and in combination with cetuximab.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TPST-1120 as Monotherapy and in Combination With Nivolumab in Subjects With Advanced Cancers
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
  • Drug: Part 2 TPST-1120 + nivolumab
    Subjects will receive escalating doses of TPST-1120 administered orally twice daily
    Other Name: Experimental + Opdivo
  • Drug: Part 3 TPST-1120
    Selected dose of TPST-1120 administered orally twice daily until disease progression
    Other Name: Experimental
  • 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
Study Arms  ICMJE
  • 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
    Intervention: Drug: Part 1 TPST-1120
  • 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.
    Intervention: Drug: Part 2 TPST-1120 + nivolumab
  • Experimental: Part 3 TPST-1120
    Selected dose of TPST-1120 administered orally twice daily until disease progression
    Intervention: Drug: Part 3 TPST-1120
  • 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
    Intervention: Drug: Part 4 TPST-1120 + nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 22, 2020)
138
Original Estimated Enrollment  ICMJE
 (submitted: February 1, 2019)
338
Estimated Study Completion Date  ICMJE June 23, 2024
Estimated Primary Completion Date February 18, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tempest Clinical Trial Support 415-798-8589 ext 122 1120-Inquiries@tempesttx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03829436
Other Study ID Numbers  ICMJE TPST-1120-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Tempest Therapeutics
Study Sponsor  ICMJE Tempest Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Robert Stagg, PharmD Tempest Therapeutics
PRS Account Tempest Therapeutics
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP