TPST-1120 as Monotherapy and in Combination With Nivolumab in Subjects With Advanced Cancers

NCT ID: NCT03829436

Last Updated: 2023-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-20
• Study Completion Date: 2022-09-07

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 TPST-1120

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

Group Type: EXPERIMENTAL

Part 1 TPST-1120

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Part 2 TPST-1120 + nivolumab

Intervention Type: DRUG

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

Part 3 TPST-1120

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

Group Type: EXPERIMENTAL

Part 3 TPST-1120

Intervention Type: DRUG

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

Part 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

Group Type: EXPERIMENTAL

Part 4 TPST-1120 + nivolumab

Intervention Type: DRUG

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

Interventions

Part 1 TPST-1120

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

Intervention Type: DRUG

Part 2 TPST-1120 + nivolumab

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

Intervention Type: DRUG

Part 3 TPST-1120

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

Intervention Type: DRUG

Part 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

Intervention Type: DRUG

Other Intervention Names

Experimental; Experimental + Opdivo; Experimental; Experimental + Opdivo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tempest Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Stagg, PharmD

Role: STUDY_DIRECTOR

Tempest Therapeutics

Locations

University of California - San Francisco

San Francisco, California, United States

Miami Cancer Institute

Miami, Florida, United States

Johns Hopkins University

Baltimore, Maryland, United States

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Columbia University Medical Center

New York, New York, United States

Carolina BioOncology Institute

Huntersville, North Carolina, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Sarah Cannon Research Institute - TN

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

TPST-1120-001

Identifier Type: -

Identifier Source: org_study_id