NCT03829436

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at P50-P75 for phase_1 hepatocellular-carcinoma

Timeline
Completed

Started Mar 2019

Typical duration for phase_1 hepatocellular-carcinoma

Geographic Reach
1 country

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 30, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 4, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

March 20, 2019

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 7, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 7, 2022

Completed
Last Updated

July 3, 2023

Status Verified

June 1, 2023

Enrollment Period

3.5 years

First QC Date

January 30, 2019

Last Update Submit

June 28, 2023

Conditions

Outcome Measures

Primary Outcomes (3)

  • 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.

    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.

    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.

    From start of treatment to end of treatment, up to 36 months

  • Identify the maximum tolerated dose

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

    From start of treatment to end of treatment, up to 36 months

Secondary Outcomes (3)

  • Assess pharmacokinetics: Maximum serum concentration (Cmax)

    Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3 (cycle can be 21 or 28 days, depending on cohort assignment)

  • Assess pharmacokinetics: Area under the curve (AUC)

    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)

  • Objective response rate

    From start of treatment to end of treatment, up to 36 months

Study Arms (4)

Part 1 TPST-1120

EXPERIMENTAL

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

Part 2 TPST-1120 + nivolumab

EXPERIMENTAL

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.

Drug: Part 2 TPST-1120 + nivolumab

Part 3 TPST-1120

EXPERIMENTAL

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

Drug: Part 3 TPST-1120

Part 4 TPST-1120 + nivolumab

EXPERIMENTAL

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 4 TPST-1120 + nivolumab

Interventions

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

Also known as: Experimental
Part 1 TPST-1120

Subjects will receive escalating doses of TPST-1120 administered orally twice daily

Also known as: Experimental + Opdivo
Part 2 TPST-1120 + nivolumab

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

Also known as: Experimental
Part 3 TPST-1120

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

Also known as: Experimental + Opdivo
Part 4 TPST-1120 + nivolumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

University of California - San Francisco

San Francisco, California, 94158, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Columbia University Medical Center

New York, New York, 10024, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Sarah Cannon Research Institute - TN

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Carcinoma, HepatocellularCarcinoma, Renal CellCarcinoma, Non-Small-Cell LungColorectal NeoplasmsSquamous Cell Carcinoma of Head and NeckTriple Negative Breast NeoplasmsCarcinoma, Transitional CellCholangiocarcinomaPancreatic NeoplasmsSarcoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver DiseasesKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesCarcinoma, Squamous CellHead and Neck NeoplasmsBreast NeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesEndocrine Gland NeoplasmsPancreatic DiseasesEndocrine System DiseasesNeoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Robert Stagg, PharmD

    Tempest Therapeutics

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 30, 2019

First Posted

February 4, 2019

Study Start

March 20, 2019

Primary Completion

September 7, 2022

Study Completion

September 7, 2022

Last Updated

July 3, 2023

Record last verified: 2023-06

Data Sharing

IPD Sharing
Will not share

Locations