Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    TPST-1495-001
Previous Study | Return to List | Next Study

Phase 1a/1b Study of TPST-1495 in Subjects With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04344795
Recruitment Status : Recruiting
First Posted : April 14, 2020
Last Update Posted : April 22, 2021
Sponsor:
Information provided by (Responsible Party):
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 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 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.

Condition or disease Intervention/treatment Phase
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 Drug: TPST-1495 twice daily Drug: TPST-1495 once daily or on intermittent schedule Phase 1

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 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 administration schedules and determine an RP2D for the selected schedule. The Expansion stage will evaluate the activity of TPST-1495 at the selected schedule and dose in disease-specific cohorts.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 117 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: open-label dose escalation, schedule and dose optimization, and dose expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1a/1b Open Label Dose-escalation and Expansion Study of TPST-1495 as a Single Agent in Subjects With Solid Tumors
Actual Study Start Date : May 6, 2020
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : July 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TPST-1495 monotherapy dose escalation
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 administered orally twice daily

Experimental: TPST-1495 monotherapy dose and schedule optimization
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 administered orally once daily or on intermittent schedule

Experimental: TPST-1495 monotherapy dose expansion
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 administered orally once daily or on intermittent schedule




Primary Outcome Measures :
  1. Determination of maximum tolerated dose and/or recommended Phase 2 dose (RP2D) and optimum dose schedule for TPST-1495 [ Time Frame: 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 based on dose limiting toxicities


Secondary Outcome Measures :
  1. Incidence of adverse events and serious adverse events as assessed by NCI-CTCAE v.5.0 [ Time Frame: 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

  2. Assess pharmacokinetics: maximum serum concentration (Cmax) [ Time Frame: From start of treatment to treatment termination visit, up to 24 months ]
    Maximum serum concentration (Cmax) of TPST-1495

  3. Assess pharmacokinetics: area under the serum concentration-time curve (AUC) [ Time Frame: From start of treatment to treatment termination visit, up to 24 months ]
    Area under the serum concentration-time curve (AUC) of TPST-1495

  4. Assess pharmacokinetics: Clearance (CL) [ Time Frame: From start of treatment to treatment termination visit, up to 24 months ]
    Clearance (CL) of TPST-1495

  5. Assess pharmacokinetics: terminal elimination half-life (t 1/2) [ Time Frame: From start of treatment to treatment termination visit, up to 24 months ]
    Terminal elimination half-life (t 1/2) of TPST-1495

  6. Overall response rate (ORR) using RECIST version 1.1 [ Time Frame: 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

  7. Progression free survival (PFS) [ Time Frame: 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)

  8. Duration of response (DoR) [ Time Frame: 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Subjects must meet all the following inclusion criteria to be eligible:

  1. 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 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.
  2. Subjects must have a tumor that is at least 1 cm in a single dimension and is radiographically apparent on CT or MRI.
  3. Eastern Cooperative Oncology Group performance status of 0 or 1 at treatment initiation.
  4. Life expectancy estimated to be ≥ 12 weeks
  5. 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.

Subjects who meet any of the following exclusion criteria will not be eligible to receive investigational product:

  1. 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.
  2. Received more than 4 doses of nonsteroidal anti-inflammatory drugs or COX-2 inhibitors within 2 weeks prior to study treatment initiation.
  3. History of allergy or hypersensitivity, GI bleed, or ulceration secondary to nonsteroidal anti-inflammatory drugs or COX-2 inhibitors.
  4. 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
  5. History of diverticulitis or any GI bleed within 2 years of treatment initiation.
  6. 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
  7. Subjects with active or untreated central nervous system (CNS) metastases
  8. New York Heart Association Classification II, III or IV.
  9. Baseline QTcF > 470 milliseconds
  10. 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).
  11. 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.
  12. Known human immunodeficiency virus (HIV) infection, active Hepatitis B (HBV), or hepatitis C (HCV). Active HBV is defined as a known positive HBsAg result. Active HCV is defined by a known positive HCV antibody result and known quantitative HCV RNA results greater than the lower limits of detection of the assay. Patients receiving antiviral therapy for Hepatitis B or C also are not eligible
  13. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations including a history of substance abuse that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  14. Subjects who are receiving anti-coagulant therapy or who are considered to be at increased risk of bleeding (i.e bleeding disorder or coagulopathy).
  15. Administration of the following substrates for drug transporters OATP1B1 and OATP1B3 is prohibited while on study or within 7 days of treatment initiation: glyburide, digoxin, docetaxel, paclitaxel, pitavastatin, rosuvastatin, simvastatin or saquinavir

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04344795


Contacts
Layout table for location contacts
Contact: Tempest Clinical Trial Support 415-798-8589 ext 122 1495-Inquiries@tempesttx.com

Locations
Layout table for location information
United States, Michigan
University of Michigan Rogel Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Brandy Slusser    734-936-9499    slusserb@med.umich.edu   
START Midwest Recruiting
Grand Rapids, Michigan, United States, 49546
Contact: Yvette Cole    616-389-1652    yvette.cole@startmidwest.com   
United States, North Carolina
Carolina BioOncology Institute Recruiting
Huntersville, North Carolina, United States, 28078
Contact: Sophia Jean-Francois, BS    980-441-1149    sjean-francois@carolinabiooncology.org   
United States, Oklahoma
SCRI-OK Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Laura Deaver    405-271-8001 ext 30488    Laura-Deaver@ouhsc.edu   
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Sarah Brodeur    412-623-2944    brodeurs@upmc.edu   
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Referrals       DDUreferrals@sarahcannon.com   
United States, Texas
South Texas Accelerated Research Therapeutics (START) Recruiting
San Antonio, Texas, United States, 78229
Contact: Edwin F Blanco-Cepeda, BSN, RN    210-593-2547    Edwin.BlancoCepeda@startsa.com   
Sponsors and Collaborators
Tempest Therapeutics
Investigators
Layout table for investigator information
Study Director: Samuel Whiting, MD PhD Tempest Therapeutics
Layout table for additonal information
Responsible Party: Tempest Therapeutics
ClinicalTrials.gov Identifier: NCT04344795    
Other Study ID Numbers: TPST-1495-001
First Posted: April 14, 2020    Key Record Dates
Last Update Posted: April 22, 2021
Last Verified: April 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tempest Therapeutics:
TPST-1495
EP2 antagonist
EP4 antagonist
prostaglandin E2 (PGE2)
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Adenocarcinoma
Endometrial Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Carcinoma, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Diseases
Head and Neck Neoplasms