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

Learn more about:
Related Clinical Trial
A Study of IMU-201 (PD1-Vaxx), a B-Cell Immunotherapy, in Adults With Non-Small Cell Lung Cancer Adherence to Survivorship Care Guidelines in Health Care Providers for Non-Small Cell Lung Cancer and Colorectal Cancer Survivor Care Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Icotinib for Completed Resected IB NSCLC With EGFR Mutation Circulating Tumor DNA in Patients at High Risk for Lung Cancer Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer Erlotinib and Radiation Therapy Plus Combination Chemotherapy in Treating Patients With Inoperable Stage III Non-Small Cell Lung Cancer Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Advanced, Metastatic, or Recurrent Non-Small Cell Lung Cancer Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer Phase I IGART Study Using Active Breathing Control and Simultaneous Boost for Patients With NSCLC Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery Bevacizumab, Paclitaxel, Carboplatin, and Radiation Therapy to the Chest in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery QUILT-3.017: Study of NEO-201 in Solid Tumors Photodynamic Therapy in Treating Patients With Lung Cancer Vaccine Treatment for Advanced Non-Small Cell Lung Cancer S1300: Pemetrexed Disodium With or Without Crizotinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer That Has Progressed After Crizotinib Single Agent Chemotherapy +/- Nivolumab in Patients With Advanced Squamous or Non-squamous NSCLC With Primary Resistance to Prior PD-1 or PDL-1 Inhibitor Comparison of Different Types of Surgery in Treating Patients With Early-stage Non-small Cell Lung Cancer Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy of NSCLC Patients in China ALK/ROS1/MET Mutations on Plasma ctDNA in Patients With NSCLC The Tracking Molecular Evolution for NSCLC (T-MENC) Study Phase 1a/1b Study of TPST-1495 Alone and With Pembrolizumab in Subjects With Solid Tumors An Integrated Approach to Treating Recurrent Thoracic Carcinomas Resistant to Tyrosine Kinase Inhibitors Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer LMB-100 Followed by Pembrolizumab in the Treatment of Adults With Mesothelin-Expressing Non-Squamous Non-Small Cell Lung Cancer (NSCLC) P2 of RMT in Combo w Durvalumab or Durva + Chemo in Untreated Adenocarcinoma NSCLC Feasibility and Safety of Nintedanib in Combination With Nivolumab in Pretreated Patients With Advanced or Metastatic NSCLC of Adenocarcinoma Histology Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer Combination Nab-paclitaxel (N-P) and Nintedanib or N-P and Placebo in Relapsed NSCLC Adenocarcinoma Prospective Radiological Study of HRCT to Predict Pathological Noninvasiveness in NSCLC To Compare Efficacy and Safety of CT-P16 and EU-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer Hsp90 Inhibitor AUY922 and Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer Impact of Concomitant Genetic Alterations in EGFR Mutated Adenocarcinoma by NGS Analysis: A Multicenter Study Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With Advanced NSCLC Poziotinib in Stage IV Lung Adenocarcinoma With HER2 Mutation (KASTT001) Study of Nivolumab in Combination With GM.CD40L Vaccine in Adenocarcinoma of the Lung Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung Lung Cancer Mutation Consortium Protocol The Detection of EGFR Mutations in Liquid Based Cytology Samples NOV120101 (Poziotinib) for 1st Line Monotherapy in Patients With Lung Adenocarcinoma A Safety and Efficacy Study of Farletuzumab in Subjects With Adenocarcinoma of the Lung Study of Vintafolide (MK-8109, EC145) in Participants With Progressive Adenocarcinoma of the Lung (MK-8109-008, EC-FV-03) Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma The Study of Apatinib Plus CIK as the Third Line Therapy for Advanced Lung Adenocarcinoma Patients With Wild-Type EGFR Telomere Biology in Early Adenocarcinoma of the Lung

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

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.
    

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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Determination of maximum tolerated dose based on dose limiting toxicities

Secondary Outcome

 Incidence of adverse events and serious adverse events as assessed by NCI-CTCAE v.5.0

Condition

Solid Tumor

Intervention

TPST-1495

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

60

Start Date

May 6, 2020

Completion Date

July 31, 2022

Primary Completion Date

August 31, 2021

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Robert Stagg, PharmD, 415-798-8589, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04344795

Organization ID

TPST-1495-001


Responsible Party

Sponsor

Study Sponsor

Tempest Therapeutics


Study Sponsor

Robert Stagg, PharmD, Study Director, Tempest Therapeutics


Verification Date

May 2020