Clinical trial NCT03829436: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Tempest Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-02-04
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab.
timeFrame: From start of treatment to end of treatment, up to 36 months
measure: 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.
timeFrame: From start of treatment to end of treatment, up to 36 months
measure: Identify the maximum tolerated dose
timeFrame: From start of treatment to end of treatment, up to 36 months
Secondary outcomes:
measure: Assess pharmacokinetics: Maximum serum concentration (Cmax)
timeFrame: Day 1, 2, 8 of Cycle 1 and Day 1 of Cycle 3 (cycle can be 21 or 28 days, depending on cohort assignment)
measure: Assess pharmacokinetics: Area under the curve (AUC)
timeFrame: 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)
measure: Objective response rate
timeFrame: From start of treatment to end of treatment, up to 36 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania Perelman School of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - TN
state: Tennessee
Study officials:
affiliation: Tempest Therapeutics
name: Robert Stagg, PharmD
role: STUDY_DIRECTOR
References: