Phase 1a/1b Study of TPST-1495 as a Single Agent and in Combination With Pembrolizumab in Subjects With Solid Tumors

Phase 1

Completed

• Conditions: Endometrial Cancer; Gastric Adenocarcinoma; Solid Tumor; Colorectal Cancer; Squamous Cell Carcinoma of Head and Neck; Non Small Cell Lung Cancer; Urothelial Carcinoma; Solid Tumors With PIK3Ca Mutation; Gastroesophageal Junction Adenocarcinoma
• Interventions: Drug: TPST-1495 once daily or on intermittent schedule; Drug: TPST-1495 twice daily; Drug: Pembrolizumab

• Registration Number: NCT04344795
• Lead Sponsor: Tempest Therapeutics

Brief Summary

This is a first-in-human Phase 1a/1b, multicenter, open-label, dose-escalation, dose and schedule optimization, and expansion study of TPST-1495 as a single agent and in combination with pembrolizumab to determine its maximum tolerated dose (MTD) and or recommended Phase 2 dose (RP2D), safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity in subjects with advanced solid tumors. Subjects with all histologic types of solid tumors are eligible for the escalation and dose-finding portions of the study. However, the preferred tumor types for enrollment are colorectal cancer (CRC), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial cancer, endometrial cancer, and gastroesophageal junction (GEJ) or gastric adenocarcinoma. Enrollment in the expansion cohorts is limited to the following tumor types: endometrial, SCCHN, CRC, and a basket cohort in subjects selected for an activating mutation in PIK3Ca.

Detailed Description

This is a first-in-human Phase 1a/1b, multicenter, open-label, dose-escalation, dose and schedule optimization, and expansion study of TPST-1495 as a single agent and in combination with pembrolizumab to determine its MTD, safety, tolerability, pharmacokinetics (PD), pharmacodynamics (PK) and preliminary anti-tumor activity in subjects with advanced solid tumors. Subjects with all histologic types of solid tumors are eligible for the study. However, the preferred tumor types for enrollment are colorectal cancer (CRC), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial cancer, endometrial cancer, and gastroesophageal junction (GEJ) or gastric adenocarcinoma. Tumor prostaglandin production and downstream signaling in both tumor cells and other cell types, including immune suppressive cell population in the tumor microenvironment, is thought to be a principal driver of progression in each of these selected malignancies. To be eligible, subjects must have no remaining standard therapy known to confer clinical benefit.

The study is composed of 3 stages. The Dose-Escalation stage will determine the MTD of single-agent TPST-1495 administered twice a day (BID). The Schedule and Dose Optimization stage will evaluate alternative TPST-1495 single-agent administration schedules and determine an RP2D for the selected schedule. This arm will also evaluate TPST-1495 in combination with pembrolizumab. The Expansion stage will evaluate the activity of TPST-1495 as a single agent and in combination with pembrolizumab at the selected schedule and dose in disease-specific cohorts and in a basket cohort in subjects selected for an activating mutation in PIK3Ca.

Study Timeline

• Study First Submitted: 2020-04-07
• Study First Submitted QC: 2020-04-09
• Study First Posted: 2020-04-14
• Study Start: 2020-05-06
• Primary Completion: 2024-09-25
• Study Completion: 2024-09-25
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-05
• Last Update Posted: 2025-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 89

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
TPST-1495 monotherapy dose and schedule optimization	TPST-1495 once daily or on intermittent schedule	Subjects will receive alternative TPST-1495 administration schedules until RP2D for the selected schedule is determined or until disease progression.
TPST-1495 monotherapy dose escalation	TPST-1495 twice daily	Subjects will receive escalating doses of TPST-1495 administered orally twice daily until maximum tolerated dose is reached or until disease progression
TPST-1495 monotherapy dose expansion	TPST-1495 once daily or on intermittent schedule	Subjects will receive selected dose regimen from dose and schedule optimization stage until disease progression
TPST-1495 in combination with pembrolizumab dose expansion	TPST-1495 once daily or on intermittent schedule	Subjects will receive selected dose regimen from dose and schedule optimization stage until disease progression
TPST-1495 in combination with pembrolizumab dose and schedule optimization	TPST-1495 once daily or on intermittent schedule	Subjects will receive alternative TPST-1495 administration schedules in combination with pembrolizumab until RP2D for the selected schedule is determined or until disease progression.
TPST-1495 in combination with pembrolizumab dose and schedule optimization	Pembrolizumab	Subjects will receive alternative TPST-1495 administration schedules in combination with pembrolizumab until RP2D for the selected schedule is determined or until disease progression.
TPST-1495 in combination with pembrolizumab dose expansion	Pembrolizumab	Subjects will receive selected dose regimen from dose and schedule optimization stage until disease progression

Primary Outcome Measures

Name	Time	Method
Determination of maximum tolerated dose and/or recommended Phase 2 dose (RP2D) and optimum dose schedule for TPST-1495 as a single agent and in combination with pembrolizumab	From start of treatment to treatment termination visit, up to 24 months	Determination of maximum tolerated dose and/or recommended Phase 2 dose (RP2D) and optimum dose schedule for TPST-1495 as a single agent and in combination with pembrolizumab based on dose limiting toxicities

Secondary Outcome Measures

Name	Time	Method
Assess pharmacokinetics: terminal elimination half-life (t 1/2)	From start of treatment to treatment termination visit, up to 24 months	Terminal elimination half-life (t 1/2) of TPST-1495
Overall response rate (ORR) using RECIST version 1.1	From start of treatment to treatment termination visit, up to 24 months	Preliminary efficacy of TPST-1495 as a single agent and in combination with pembrolizumab as assessed by overall response rate (ORR) using RECIST version 1.1
Progression free survival (PFS)	From start of treatment to treatment termination visit, up to 24 months	Preliminary efficacy of TPST-1495 as a single agent and in combination with pembrolizumab as assessed by progression free survival (PFS)
Incidence of adverse events and serious adverse events as assessed by NCI-CTCAE v.5.0	From start of treatment to treatment termination visit, up to 24 months	Incidence of treatment-emergent adverse events and serious adverse events for TPST-1495
Assess pharmacokinetics: maximum serum concentration (Cmax)	From start of treatment to treatment termination visit, up to 24 months	Maximum serum concentration (Cmax) of TPST-1495
Assess pharmacokinetics: area under the serum concentration-time curve (AUC)	From start of treatment to treatment termination visit, up to 24 months	Area under the serum concentration-time curve (AUC) of TPST-1495
Assess pharmacokinetics: Clearance (CL)	From start of treatment to treatment termination visit, up to 24 months	Clearance (CL) of TPST-1495
Duration of response (DoR)	From start of treatment to treatment termination visit, up to 24 months	Preliminary efficacy of TPST-1495 as a single agent and in combination with pembrolizumab as assessed by duration of response (DoR)

Trial Locations

Locations (11)

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Baystate Gynecologic Oncology; 🇺🇸 Springfield, Massachusetts, United States

University of Michigan Rogel Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Carolina BioOncology Institute; 🇺🇸 Huntersville, North Carolina, United States

SCRI-OK Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

University of Pennsylvania Perelman School of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

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