TPST-1120 as Monotherapy and in Combination With (Nivolumab, Docetaxel or Cetuximab) in Subjects With Advanced Cancers

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

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