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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
Secondary Outcome
Assess pharmacokinetics: Maximum serum concentration (Cmax)
Condition
Hepatocellular Carcinoma
Intervention
Part 1 TPST-1120
Study Arms / Comparison Groups
Part 1 TPST-1120
Description: Subjects will receive escalating doses of TPST-1120 administered orally twice daily continuously until MTD is reached or until disease progression
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
138
Start Date
March 20, 2019
Completion Date
June 23, 2024
Primary Completion Date
September 7, 2022
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Robert Stagg, PharmD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03829436
Organization ID
TPST-1120-001
Responsible Party
Sponsor
Study Sponsor
Tempest Therapeutics
Study Sponsor
Robert Stagg, PharmD, Study Director, Tempest Therapeutics
Verification Date
November 2022