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

• ClinicalTrials.gov Identifier: NCT03829436
• Recruitment Status: Completed
• First Posted: February 4, 2019
• Last Update Posted: July 3, 2023
• Sponsor: Tempest Therapeutics
• Information provided by (Responsible Party): Tempest Therapeutics

Tracking Information

• First Submitted Date: January 30, 2019
• First Posted Date: February 4, 2019
• Last Update Posted Date: July 3, 2023
• Actual Study Start Date: March 20, 2019
• Actual Primary Completion Date: September 7, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 22, 2020)

• 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.
• 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.
• 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.

Original Primary Outcome Measures (submitted: February 1, 2019)

• Incidence of dose limiting toxicities (DLTs) of TPST-1120 as a single agent and in combination with nivolumab, in combination with docetaxel and in combination with cetuximab. [ 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, in combination with docetaxel and in combination with cetuximab.
• Incidence of treatment-emergent adverse events as assessed by NCI-CTCAE v5.0 of TSPT-1120 as a single agent and in combination with nivolumab, in combination with docetaxel and in combination with cetuximab. [ 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 TSPT-1120 as a single agent and in combination with nivolumab, in combination with docetaxel and in combination with cetuximab.
• 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, in combination with docetaxel and in combination with cetuximab.

Current Secondary Outcome Measures (submitted: June 22, 2020)

• 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
• 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
• 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.

Original Secondary Outcome Measures (submitted: February 1, 2019)

• Assess pharmacokinetics: Area under the curve (AUC) [ 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) ]
  Area under the curve (AUC) of TSPT-1120
• 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 TSPT-1120
• 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 TSPT-1120 as a single agent and in combination with nivolumab, in combination with docetaxel and in combination with cetuximab.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

• 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 Name: Experimental
• Drug: Part 2 TPST-1120 + nivolumab
  Subjects will receive escalating doses of TPST-1120 administered orally twice daily
  Other Name: Experimental + Opdivo
• Drug: Part 3 TPST-1120
  Selected dose of TPST-1120 administered orally twice daily until disease progression
  Other Name: Experimental
• 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 Name: Experimental + Opdivo

Study Arms

• 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
  Intervention: Drug: Part 1 TPST-1120
• 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.
  Intervention: Drug: Part 2 TPST-1120 + nivolumab
• Experimental: Part 3 TPST-1120
  Selected dose of TPST-1120 administered orally twice daily until disease progression
  Intervention: Drug: Part 3 TPST-1120
• 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
  Intervention: Drug: Part 4 TPST-1120 + nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 28, 2023): 38
• Original Estimated Enrollment (submitted: February 1, 2019): 338
• Actual Study Completion Date: September 7, 2022
• Actual Primary Completion Date: September 7, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03829436
• Other Study ID Numbers: TPST-1120-001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Tempest Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Tempest Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Robert Stagg, PharmD; Tempest Therapeutics

• PRS Account: Tempest Therapeutics
• Verification Date: June 2023