Cholangiocarcinoma, Colorectal Cancer, GastroEsophageal Cancer, Hepatocellular Carcinoma, Metastatic Castration Resistant Prostate Cancer, Non-small Cell Lung Cancer, Pancreatic Cancer, Renal Cell Carcinoma, Sarcoma, Squamous Cell Carcinoma of Head and Neck, Triple-Negative Breast Cancer, Urothelial Carcinoma
Conditions
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.
Interventions
DRUGPart 1 TPST-1120
Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
DRUGPart 2 TPST-1120 + nivolumab
Subjects will receive escalating doses of TPST-1120 administered orally twice daily
DRUGPart 3 TPST-1120
Selected dose of TPST-1120 administered orally twice daily until disease progression
DRUGPart 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
Sponsors
Tempest Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identify the maximum tolerated dose | 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 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 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Maximum serum concentration (Cmax) of TPST-1120 |
| 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) | Area under the curve (AUC) of TPST-1120 |
| Objective response rate | 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. |
Countries
United States
Outcome results
None listed