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

Tempest Therapeutics

Status and phase: Completed; Phase 1

Conditions: Metastatic Castration Resistant Prostate Cancer; Urothelial Carcinoma; Cholangiocarcinoma; Triple-Negative Breast Cancer; Sarcoma; Squamous Cell Carcinoma of Head and Neck; Non-small Cell Lung Cancer; Hepatocellular Carcinoma; GastroEsophageal Cancer; Renal Cell Carcinoma; Pancreatic Cancer; Colorectal Cancer

Treatments: Drug: Part 3 TPST-1120; Drug: Part 1 TPST-1120; Drug: Part 4 TPST-1120 + nivolumab; Drug: Part 2 TPST-1120 + nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03829436

TPST-1120-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 38 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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38 participants in 4 patient groups

Part 1 TPST-1120

Experimental group

Description:

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

Treatment:

Drug: Part 1 TPST-1120

Part 2 TPST-1120 + nivolumab

Experimental group

Description:

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.

Treatment:

Drug: Part 2 TPST-1120 + nivolumab

Part 3 TPST-1120

Experimental group

Description:

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

Treatment:

Drug: Part 3 TPST-1120

Part 4 TPST-1120 + nivolumab

Experimental group

Description:

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

Treatment:

Drug: Part 4 TPST-1120 + nivolumab