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Trial record 1 of 1 for:    tpst1495
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Phase 1a/1b Study of TPST-1495 Alone and With Pembrolizumab in Subjects With Solid Tumors

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ClinicalTrials.gov Identifier: NCT04344795
Recruitment Status : Recruiting
First Posted : April 14, 2020
Last Update Posted : May 15, 2020
Sponsor:
Information provided by (Responsible Party):
Tempest Therapeutics

Brief Summary:
This is a first-in-human Phase 1a/1b, multicenter, open-label, dose-escalation and expansion study of TPST-1495 administered as a single agent and in combination with pembrolizumab to determine its maximum tolerated dose (MTD), 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 microsatellite-stable colorectal cancer (MSS CRC), adenocarcinoma of the lung, squamous cell carcinoma of the head and neck (SCCHN), bladder cancer, triple negative breast cancer (TNBC) and gastric cancer.

Condition or disease Intervention/treatment Phase
Solid Tumor Microsatellite-stable Colorectal Cancer (MSS CRC) Adenocarcinoma of the Lung Squamous Cell Carcinoma of Head and Neck Bladder Cancer Triple Negative Breast Cancer Gastric Cancer Drug: TPST-1495 Drug: Pembrolizumab Phase 1

Detailed Description:
This is a first-in-human Phase 1a/1b, multicenter, open-label, dose-escalation and expansion study of TPST-1495 administered 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 microsatellite-stable colorectal cancer (MSS CRC), adenocarcinoma of the lung, squamous cell carcinoma of the head and neck (SCCHN), bladder cancer, triple negative breast cancer (TNBC) and gastric cancer. To be eligible, subjects must have no remaining standard known to confer clinical benefit. This trial is composed of dose escalation and dose expansion cohorts.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: open-label dose escalation 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 and in Combination With Pembrolizumab 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
TPST-1495 administered orally twice daily

Experimental: TPST-1495 in combination with pembrolizumab dose escalation
Subjects will receive escalating doses of TPST-1495 administered orally twice daily in combination with pembrolizumab administered by IV infusion until maximum tolerated dose is reached or until disease progression
Drug: TPST-1495
TPST-1495 administered orally twice daily

Drug: Pembrolizumab
Pembrolizumab administered intravenously once every 3 weeks
Other Name: Keytruda

Experimental: TPST-1495 monotherapy dose expansion
Subjects will receive selected dose of TPST-1495 administered orally twice daily until disease progression
Drug: TPST-1495
TPST-1495 administered orally twice daily

Experimental: TPST-1495 in combination with pembrolizumab dose expansion
Subjects will receive selected dose of TPST-1495 administered orally twice daily in combination with pembrolizumab administered by IV infusion until disease progression
Drug: TPST-1495
TPST-1495 administered orally twice daily

Drug: Pembrolizumab
Pembrolizumab administered intravenously once every 3 weeks
Other Name: Keytruda




Primary Outcome Measures :
  1. Determination of maximum tolerated dose based on dose limiting toxicities [ Time Frame: From start of treatment to treatment termination visit, up to 24 months ]
    Determination of maximum tolerated dose of 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 as a single agent and in combination with pembrolizumab

  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

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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 MSS colorectal cancer, squamous cell carcinoma of the head and neck, bladder cancer and triple negative breast cancer and gastric cancer. Prior anti PD-1 or PDL-1 is permitted provided that the subject did not discontinue prior therapies due to immune-related adverse events.
  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 enrollment
  4. Life expectancy ≥ 12 weeks
  5. Subjects must have received their last chemotherapy, biologic therapy or investigational therapy at least 4 weeks prior to enrollment.
  6. Adequate organ and marrow function (subjects must not have received transfusions or growth factor support within 14 days prior to first dose of investigational product) as defined below:

    • 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× institutional 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. The use of an investigational device or agent must be stopped at least 4 weeks prior to enrollment.
  2. Chronic use (i.e., daily for 7 days or more) of nonsteroidal anti-inflammatory drugs or COX-2 inhibitors within 2 weeks of enrollment.
  3. Gastrointestinal ulcer or active colitis within 28 days of enrollment.
  4. New York Heart Association Classification II, III or IV.
  5. Baseline QTcF > 470 milliseconds
  6. Receipt of live attenuated vaccines within 30 days prior to the first dose of investigational product
  7. Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease (e.g., colitis or Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)
  8. Active infection requiring therapy (including tuberculosis) or positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C antibody test and hepatitis C (HCV) ribonucleic acid (RNA) test1. The HCV RNA test will be performed only for patients who have positive HCV antibody test. Patients with a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening are eligible for the study.
  9. 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.
  10. Administration of the following drugs is prohibited while taking TPST 1495: glyburide, cefaclor, cefonicid, cefoxitin, cephradine, cidofovir, zidovudine, 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
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Contact: Tempest Clinical Trial Support 415-798-8589 ext 122 1495-Inquiries@tempesttx.com

Locations
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United States, Michigan
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, 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
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Study Director: Robert Stagg, PharmD Tempest Therapeutics
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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: May 15, 2020
Last Verified: May 2020

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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:
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Adenocarcinoma
Triple Negative Breast Neoplasms
Adenocarcinoma of Lung
Squamous Cell Carcinoma of Head and Neck
Neoplasms
Neoplasms by Site
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Breast Neoplasms
Breast Diseases
Skin Diseases
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Head and Neck Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents