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

Primary Purpose

Hepatocellular Carcinoma, Metastatic Castration Resistant Prostate Cancer, Renal Cell Carcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Part 1 TPST-1120
Part 2 TPST-1120 + nivolumab
Part 3 TPST-1120
Part 4 TPST-1120 + nivolumab
Sponsored by
Tempest Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California - San Francisco
  • Miami Cancer Institute
  • Johns Hopkins University
  • University of Michigan Rogel Cancer Center
  • Columbia University Medical Center
  • Carolina BioOncology Institute
  • Stephenson Cancer Center
  • University of Pennsylvania Perelman School of Medicine
  • Thomas Jefferson University Hospital
  • UPMC Hillman Cancer Center
  • Sarah Cannon Research Institute - TN

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1 TPST-1120

Part 2 TPST-1120 + nivolumab

Part 3 TPST-1120

Part 4 TPST-1120 + nivolumab

Arm Description

Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression

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.

Selected dose of TPST-1120 administered orally twice daily until disease progression

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

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
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.
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
Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.

Secondary Outcome Measures

Assess pharmacokinetics: Maximum serum concentration (Cmax)
Maximum serum concentration (Cmax) of TPST-1120
Assess pharmacokinetics: Area under the curve (AUC)
Area under the curve (AUC) of TPST-1120
Objective response rate
Objective response rate per RECIST v1.1 criterion of TPST-1120 as a single agent and in combination with nivolumab.

Full Information

First Posted
January 30, 2019
Last Updated
June 28, 2023
Sponsor
Tempest Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT03829436
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
March 20, 2019 (Actual)
Primary Completion Date
September 7, 2022 (Actual)
Study Completion Date
September 7, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tempest Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1 TPST-1120
Arm Type
Experimental
Arm Description
Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
Arm Title
Part 2 TPST-1120 + nivolumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 3 TPST-1120
Arm Type
Experimental
Arm Description
Selected dose of TPST-1120 administered orally twice daily until disease progression
Arm Title
Part 4 TPST-1120 + nivolumab
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Part 1 TPST-1120
Other Intervention Name(s)
Experimental
Intervention Description
Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
Intervention Type
Drug
Intervention Name(s)
Part 2 TPST-1120 + nivolumab
Other Intervention Name(s)
Experimental + Opdivo
Intervention Description
Subjects will receive escalating doses of TPST-1120 administered orally twice daily
Intervention Type
Drug
Intervention Name(s)
Part 3 TPST-1120
Other Intervention Name(s)
Experimental
Intervention Description
Selected dose of TPST-1120 administered orally twice daily until disease progression
Intervention Type
Drug
Intervention Name(s)
Part 4 TPST-1120 + nivolumab
Other Intervention Name(s)
Experimental + Opdivo
Intervention Description
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
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
Description
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
Title
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.
Description
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
Title
Identify the maximum tolerated dose
Description
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
Secondary Outcome Measure Information:
Title
Assess pharmacokinetics: Maximum serum concentration (Cmax)
Description
Maximum serum concentration (Cmax) of TPST-1120
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)
Title
Assess pharmacokinetics: Area under the curve (AUC)
Description
Area under the curve (AUC) of TPST-1120
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)
Title
Objective response rate
Description
Objective response rate per RECIST v1.1 criterion 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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: Subjects must not have experienced an irAE toxicity that led to permanent discontinuation of prior immunotherapy. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Stagg, PharmD
Organizational Affiliation
Tempest Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
University of California - San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Miami Cancer Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
University of Michigan Rogel Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10024
Country
United States
Facility Name
Carolina BioOncology Institute
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Stephenson Cancer Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
University of Pennsylvania Perelman School of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
UPMC Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Sarah Cannon Research Institute - TN
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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