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

NCT04344795 | Completed Phase 1 FDA Drug

• 1 other identifier: TPST-1495-001
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 11

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.

Conditions

Solid Tumor; Colorectal Cancer; Non Small Cell Lung Cancer; Squamous Cell Carcinoma of Head and Neck; Urothelial Carcinoma; Endometrial Cancer; Gastroesophageal Junction Adenocarcinoma; Gastric Adenocarcinoma; Solid Tumors With PIK3Ca Mutation

Keywords

TPST-1495; EP2 antagonist; EP4 antagonist; prostaglandin E2 (PGE2); pembrolizumab; PIK3Ca mutation

Outcome Measures

Primary Outcomes (1)

• 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

  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

  From start of treatment to treatment termination visit, up to 24 months

Secondary Outcomes (8)

• 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

• Assess pharmacokinetics: maximum serum concentration (Cmax)

  From start of treatment to treatment termination visit, up to 24 months

• Assess pharmacokinetics: area under the serum concentration-time curve (AUC)

  From start of treatment to treatment termination visit, up to 24 months

• Assess pharmacokinetics: Clearance (CL)

  From start of treatment to treatment termination visit, up to 24 months

• Assess pharmacokinetics: terminal elimination half-life (t 1/2)

  From start of treatment to treatment termination visit, up to 24 months

Study Arms (5)

TPST-1495 monotherapy dose escalation

EXPERIMENTAL

Subjects will receive escalating doses of TPST-1495 administered orally twice daily until maximum tolerated dose is reached or until disease progression

Drug: TPST-1495 twice daily

TPST-1495 monotherapy dose and schedule optimization

EXPERIMENTAL

Subjects will receive alternative TPST-1495 administration schedules until RP2D for the selected schedule is determined or until disease progression.

Drug: TPST-1495 once daily or on intermittent schedule

TPST-1495 monotherapy dose expansion

EXPERIMENTAL

Subjects will receive selected dose regimen from dose and schedule optimization stage until disease progression

Drug: TPST-1495 once daily or on intermittent schedule

TPST-1495 in combination with pembrolizumab dose and schedule optimization

EXPERIMENTAL

Subjects will receive alternative TPST-1495 administration schedules in combination with pembrolizumab until RP2D for the selected schedule is determined or until disease progression.

Drug: TPST-1495 once daily or on intermittent schedule; Drug: Pembrolizumab

TPST-1495 in combination with pembrolizumab dose expansion

EXPERIMENTAL

Subjects will receive selected dose regimen from dose and schedule optimization stage until disease progression

Drug: TPST-1495 once daily or on intermittent schedule; Drug: Pembrolizumab

Interventions

TPST-1495 twice daily DRUG

TPST-1495 administered orally twice daily

TPST-1495 monotherapy dose escalation

TPST-1495 once daily or on intermittent schedule DRUG

TPST-1495 administered orally once daily or on intermittent schedule

TPST-1495 in combination with pembrolizumab dose and schedule optimization; TPST-1495 in combination with pembrolizumab dose expansion; TPST-1495 monotherapy dose and schedule optimization; TPST-1495 monotherapy dose expansion

Pembrolizumab DRUG

Pembrolizumab dosed per label recommendations

Also known as: Keytruda

TPST-1495 in combination with pembrolizumab dose and schedule optimization; TPST-1495 in combination with pembrolizumab dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a histologically-confirmed malignancy that is metastatic or unresectable for which there is no remaining standard therapy known to confer clinical benefit. While all solid tumor types are eligible for the dose-escalation and dose-finding portions of the study, there is a preference to enroll patients with colorectal cancer, squamous cell carcinoma of the head and neck, urothelial cancer, endometrial cancer, NSCLC, and gastric or gastroesophageal junction adenocarcinoma. The expansion cohorts are limited to the following tumor types: endometrial, SCCHN, CRC, and tumors with an activating mutation in PIK3Ca.
• Subjects must have a tumor that is at least 1 cm in a single dimension and is radiographically apparent on CT or MRI.
• Eastern Cooperative Oncology Group performance status of 0 or 1 at treatment initiation.
• Life expectancy estimated to be ≥ 12 weeks
• Adequate organ and marrow function (subjects must not have received transfusions or growth factor support within 1 month prior to first dose of investigational product) as defined below:
• Albumin ≥ 3.0 g/dL
• Hemoglobin ≥ 10.0 g/dL
• Absolute neutrophil count ≥ 1,000/mm3
• Platelet count ≥ 100,000/mm3
• Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN); for subjects with documented/suspected Gilbert's disease, bilirubin should be ≤ 2 × ULN.
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN; for subjects with liver metastases, AST or ALT ≤ 5 × ULN
• Creatinine ≤ 1.5×ULN OR calculated creatinine clearance (CrCl) ≥ 60 mL/min for subjects with creatinine levels \> 1.5× ULN.

You may not qualify if:

• 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.
• Received more than 4 doses of nonsteroidal anti-inflammatory drugs or COX-2 inhibitors within 2 weeks prior to study treatment initiation.
• History of allergy or hypersensitivity, GI bleed, or ulceration secondary to nonsteroidal anti-inflammatory drugs or COX-2 inhibitors.
• History of GI ulcer within 1 year of treatment initiation or history of untreated helicobacter pylori infection. Subjects with history of treated helicobacter pylori infection with confirmation of eradication are eligible
• History of diverticulitis or any GI bleed within 2 years of treatment initiation.
• Receipt of any anticancer therapy within the following windows:
• Small molecule tyrosine kinase inhibitor (TKI) therapy (including investigational) within 2 weeks or 5 half-lives prior to treatment initiation, whichever is longer
• Any type of anti-cancer antibody or cytotoxic chemotherapy within 4 weeks prior to treatment initiation
• Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before treatment initiation. Patients with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Other investigational therapy within 2 weeks or 5 half-lives prior to dosing, whichever is longer
• Subjects with active or untreated central nervous system (CNS) metastases
• New York Heart Association Classification II, III or IV.
• Baseline QTcF \> 470 milliseconds
• Receipt of live attenuated vaccines within 30 days prior to the first dose of investigational product. (Killed virus or other non-live vaccines are allowed (including most seasonal influenza vaccines, streptococcus pneumonia vaccines, and newly approved COVID-19 vaccines).
• Active autoimmune disease or inflammatory disorders including inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease) requiring systemic treatment (i.e., with use of disease modifying agents, systemic corticosteroids or immunosuppressive drug) within 2 years prior to treatment initiation.

Sponsors & Collaborators

• Tempest Therapeutics: lead

Study Sites (11)

University of Colorado

Aurora, Colorado, 80045, United States

Location

Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine

Baltimore, Maryland, 21287, United States

Location

Baystate Gynecologic Oncology

Springfield, Massachusetts, 01107, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

SCRI-OK Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Wang D, Cabalag CS, Clemons NJ, DuBois RN. Cyclooxygenases and Prostaglandins in Tumor Immunology and Microenvironment of Gastrointestinal Cancer. Gastroenterology. 2021 Dec;161(6):1813-1829. doi: 10.1053/j.gastro.2021.09.059. Epub 2021 Oct 2.

  PMID: 34606846 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Transitional Cell; Endometrial Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Samuel Whiting, MD PhD

  Tempest Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: open-label dose escalation, schedule and dose optimization, and dose expansion

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 14, 2020
• Study Start: May 6, 2020
• Primary Completion: September 25, 2024
• Study Completion: September 25, 2024
• Last Updated: September 12, 2025

Record last verified: 2025-09

Locations

US (11)