Hepatocellular CarcinomaPhase 1NCT03829436
TPST-1120 as Monotherapy and in Combination With Nivolumab in Subjects With Advanced Cancers
A Phase 1 study testing Part 1 TPST-1120, Part 2 TPST-1120 + nivolumab and Part 3 TPST-1120 in people with Hepatocellular Carcinoma and Metastatic Castration Resistant Prostate Cancer, run by Tempest Therapeutics at 11 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Metastatic Castration Resistant Prostate Cancer, Renal Cell Carcinoma
- What is being tested?
- Part 1 TPST-1120, Part 2 TPST-1120 + nivolumab and Part 3 TPST-1120
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 11 sitesUnited States
- Study dates
- 20 Mar 2019to 7 Sep 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Johns Hopkins University
Baltimore, Maryland, 21287
Carolina BioOncology Institute
Huntersville, North Carolina, 28078
Miami Cancer Institute
Miami, Florida, 33176
Sarah Cannon Research Institute - TN
Nashville, Tennessee, 37203
Columbia University Medical Center
New York, New York, 10024
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15213
University of California - San Francisco
San Francisco, California, 94158
About this study
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
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.
Read the 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.
- 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
- Being tested
- Part 1 TPST-1120, Part 2 TPST-1120 + nivolumab, Part 3 TPST-1120, Part 4 TPST-1120 + nivolumab
- Medical subject headings
- Carcinoma, Hepatocellular, Carcinoma, Renal Cell, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Triple Negative Breast Neoplasms, Carcinoma, Transitional Cell, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part 1 TPST-1120Drug
Also called Experimental
Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
Part 2 TPST-1120 + nivolumabDrug
Also called Experimental + Opdivo
Subjects will receive escalating doses of TPST-1120 administered orally twice daily
Part 3 TPST-1120Drug
Also called Experimental
Selected dose of TPST-1120 administered orally twice daily until disease progression
Part 4 TPST-1120 + nivolumabDrug
Also called Experimental + Opdivo
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Part 2 TPST-1120 + nivolumab |
| Part 3 TPST-1120 | Experimental | Selected dose of TPST-1120 administered orally twice daily until disease progression Receives: 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 Receives: Drug: Part 4 TPST-1120 + nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: From start of treatment to end of treatment, up to 36 months
Secondary outcomes (3)
Assess pharmacokinetics: Maximum serum concentration (Cmax)
Maximum serum concentration (Cmax) of TPST-1120
Measured: 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)
Area under the curve (AUC) of TPST-1120
Measured: 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
Objective response rate per RECIST v1.1 criterion of TPST-1120 as a single agent and in combination with nivolumab.
Measured: From start of treatment to end of treatment, up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2019
- Study start20 Mar 2019
- Primary completion7 Sep 2022
- Study completion7 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tempest Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Stagg, PharmD, Study director, Tempest Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03829436
- Sponsor's protocol ID
- TPST-1120-001
- Status last verified
- Jun 2023
- First submitted
- 30 Jan 2019
- Last updated
- 3 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03829436
- Acronym / sponsor ID
- TPST-1120-001
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Tempest TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 20 Mar 2019 (actual)
- Primary completion
- 7 Sep 2022 (actual)
- Study completion
- 7 Sep 2022 (actual)
- First posted
- 4 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 TPST-1120 | Experimental | Drug: Part 1 TPST-1120Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression |
| Part 2 TPST-1120 + nivolumab | Experimental | Drug: Part 2 TPST-1120 + nivolumabSubjects 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 3 TPST-1120 | Experimental | Drug: Part 3 TPST-1120Selected dose of TPST-1120 administered orally twice daily until disease progression |
| Part 4 TPST-1120 + nivolumab | Experimental | Drug: Part 4 TPST-1120 + nivolumabSelected 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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:
- Symptomatic, untreated or actively progressing central nervous system metastases
- Have received fibrates within 28 days before first dose of investigational agent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Part 1 TPST-1120Also: ExperimentalSubjects 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 + nivolumabAlso: Experimental + OpdivoSubjects will receive escalating doses of TPST-1120 administered orally twice daily | Drug | Part 2 TPST-1120 + nivolumab |
| Part 3 TPST-1120Also: ExperimentalSelected dose of TPST-1120 administered orally twice daily until disease progression | Drug | Part 3 TPST-1120 |
| Part 4 TPST-1120 + nivolumabAlso: Experimental + OpdivoSelected 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 |
Primary outcome
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.
3 secondary outcomes
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)
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)
Objective response rate
Time frame: From start of treatment to end of treatment, up to 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Stagg, PharmD study director
Tempest Therapeutics
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Part 1 TPST-1120, Part 2 TPST-1120 + nivolumab and Part 3 TPST-1120 in people with Hepatocellular Carcinoma and Metastatic Castration Resistant Prostate Cancer, run by Tempest Therapeutics at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2023.