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

Sponsor

Tempest Therapeutics (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03829436

Collaborator

(none)

138

Enrollment

Locations

Arms

63.1

Anticipated Duration (Months)

12.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Part 1 TPST-1120 Drug: Part 2 TPST-1120 + nivolumab Drug: Part 3 TPST-1120 Drug: Part 4 TPST-1120 + nivolumab	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

138 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 20, 2019

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jun 23, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	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 Other Names: Experimental
Experimental: 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.	Drug: Part 2 TPST-1120 + nivolumab Subjects will receive escalating doses of TPST-1120 administered orally twice daily Other Names: Experimental + Opdivo
Experimental: Part 3 TPST-1120 Selected dose of TPST-1120 administered orally twice daily until disease progression	Drug: Part 3 TPST-1120 Selected dose of TPST-1120 administered orally twice daily until disease progression Other Names: Experimental
Experimental: 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	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 Other Names: Experimental + Opdivo

Outcome Measures

Primary Outcome Measures

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]
Incidence of dose limiting toxicities (DLTs) 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]
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.
Identify the maximum tolerated dose [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 Outcome Measures

Assess pharmacokinetics: Maximum serum concentration (Cmax) [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
Assess pharmacokinetics: Area under the curve (AUC) [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
Objective response rate [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California - San Francisco	San Francisco	California	United States	94158
2	Miami Cancer Institute	Miami	Florida	United States	33176
3	Johns Hopkins University	Baltimore	Maryland	United States	21287
4	University of Michigan Rogel Cancer Center	Ann Arbor	Michigan	United States	48109
5	Columbia University Medical Center	New York	New York	United States	10024
6	Carolina BioOncology Institute	Huntersville	North Carolina	United States	28078
7	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
8	University of Pennsylvania Perelman School of Medicine	Philadelphia	Pennsylvania	United States	19104
9	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
10	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15213
11	Sarah Cannon Research Institute - TN	Nashville	Tennessee	United States	37203