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Completed

NCT Number: NCT03829436

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

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.

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Key information

Conditions

Hepatocellular Carcinoma Adenocarcinoma Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Hepatocellular Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Carcinoma, Squamous Cell Carcinoma, Transitional Cell Cholangiocarcinoma Colonic Diseases Colorectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications GastroEsophageal Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Intestinal Diseases Intestinal Neoplasms Kidney Diseases Kidney Neoplasms Liver Diseases Liver Neoplasms Lung Diseases Lung Neoplasms Male Urogenital Diseases Metastatic Castration Resistant Prostate Cancer Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Connective and Soft Tissue Neoplasms, Glandular and Epithelial Non-small Cell Lung Cancer Pancreatic Cancer Pancreatic Diseases Pancreatic Neoplasms Rectal Diseases Renal Cell Carcinoma Respiratory Tract Diseases Respiratory Tract Neoplasms Sarcoma Skin Diseases Skin and Connective Tissue Diseases Squamous Cell Carcinoma of Head and Neck Thoracic Neoplasms Triple Negative Breast Neoplasms Triple-negative Breast Cancer Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Urothelial Carcinoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of California - San Francisco, San Francisco, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • Subjects must not have experienced an irAE toxicity that led to permanent discontinuation of prior immunotherapy.
  • 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

Treatment and study plan

Part 1 TPST-1120

Drug

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

Other names: Experimental

Part 2 TPST-1120 + nivolumab

Drug

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

Other names: Experimental + Opdivo

Part 3 TPST-1120

Drug

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

Other names: Experimental

Part 4 TPST-1120 + nivolumab

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

Other names: Experimental + Opdivo

Primary outcomes

  1. Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.

    Time frame: 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.

  2. 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.

    Time frame: 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.

  3. Identify the maximum tolerated dose

    Time frame: 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.

Secondary outcomes

  1. Assess pharmacokinetics: Maximum serum concentration (Cmax)

    Time frame: 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

  2. Assess pharmacokinetics: Area under the curve (AUC)

    Time frame: 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

  3. Objective response rate

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Tempest Therapeutics

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Feb 4, 2019
Registry last updated
Jul 3, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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