Clinical Trials /

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

NCT04344795

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 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.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1a/1b Study of TPST-1495 Alone and With Pembrolizumab in Subjects With Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: TPST-1495-001
  • NCT ID: NCT04344795

Conditions

  • 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

Interventions

DrugSynonymsArms
TPST-1495TPST-1495 in combination with pembrolizumab dose escalation
PembrolizumabKeytrudaTPST-1495 in combination with pembrolizumab dose escalation

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
TPST-1495 monotherapy dose escalationExperimentalSubjects will receive escalating doses of TPST-1495 administered orally twice daily until maximum tolerated dose is reached or until disease progression
  • TPST-1495
TPST-1495 in combination with pembrolizumab dose escalationExperimentalSubjects 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
  • TPST-1495
  • Pembrolizumab
TPST-1495 monotherapy dose expansionExperimentalSubjects will receive selected dose of TPST-1495 administered orally twice daily until disease progression
  • TPST-1495
TPST-1495 in combination with pembrolizumab dose expansionExperimentalSubjects will receive selected dose of TPST-1495 administered orally twice daily in combination with pembrolizumab administered by IV infusion until disease progression
  • TPST-1495
  • Pembrolizumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determination of maximum tolerated dose based on dose limiting toxicities
Time Frame:From start of treatment to treatment termination visit, up to 24 months
Safety Issue:
Description:Determination of maximum tolerated dose of TPST-1495 based on dose limiting toxicities

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tempest Therapeutics

Trial Keywords

  • TPST-1495
  • EP2 antagonist
  • EP4 antagonist
  • prostaglandin E2 (PGE2)

Last Updated

April 13, 2020