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.
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
Drug | Synonyms | Arms |
---|
Part 1 TPST-1120 | Experimental | Part 1 TPST-1120 |
Part 2 TPST-1120 + nivolumab | Experimental + Opdivo | Part 2 TPST-1120 + nivolumab |
Part 3 TPST-1120 | Experimental | Part 3 TPST-1120 |
Part 4 TPST-1120 + nivolumab | Experimental + Opdivo | Part 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
Name | Type | Description | Interventions |
---|
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 | |
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. | - Part 2 TPST-1120 + nivolumab
|
Part 3 TPST-1120 | Experimental | Selected dose of TPST-1120 administered orally twice daily until disease progression | |
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 | - 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