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

Colorectal Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03829436
• Other study ID #: TPST-1120-001
• Status: Completed
• Phase: Phase 1
• Start date: March 20, 2019
• Est. completion date: September 7, 2022

Study information

• Verified date: June 2023
• Source: Tempest Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 anticancer agent, nivolumab, an anti-PD1 antibody, in subjects with advanced solid tumors.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: September 7, 2022
• Est. primary completion date: September 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• 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 Neoplasms
• Triple-Negative Breast Cancer
• Urothelial Carcinoma

Intervention

Drug:
• 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
• Part 2 TPST-1120 + nivolumab
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
• 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

Locations

Country	Name	City	State
United States	University of Michigan Rogel Cancer Center	Ann Arbor	Michigan
United States	Johns Hopkins University	Baltimore	Maryland
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Miami Cancer Institute	Miami	Florida
United States	Sarah Cannon Research Institute - TN	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania Perelman School of Medicine	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	University of California - San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Tempest Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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.	From start of treatment to end of treatment, up to 36 months
Primary	Identify the maximum tolerated dose	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
Secondary	Assess pharmacokinetics: Maximum serum concentration (Cmax)	Maximum serum concentration (Cmax) of TPST-1120	Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3 (cycle can be 21 or 28 days, depending on cohort assignment)
Secondary	Assess pharmacokinetics: Area under the curve (AUC)	Area under the curve (AUC) of TPST-1120	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)
Secondary	Objective response rate	Objective response rate per RECIST v1.1 criterion of TPST-1120 as a single agent and in combination with nivolumab.	From start of treatment to end of treatment, up to 36 months