Clinical Trials /

Study of Vactosertib in Combination With Durvalumab in Advanced NSCLC

NCT03732274

Description:

This is an open -label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib in Combination with durvalumab in patients advanced NSCLC who progressed following platinum-based chemotherapy.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Vactosertib in Combination With Durvalumab in Advanced NSCLC
  • Official Title: Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib in Combination With Durvalumab in Patients With Advanced Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: MP-VAC-203
  • NCT ID: NCT03732274

Conditions

  • Non-Small Cell Lung Cancer Metastatic

Interventions

DrugSynonymsArms
TEW-7197vactosetibDose Escalation of TEW-7197

Purpose

This is an open -label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib in Combination with durvalumab in patients advanced NSCLC who progressed following platinum-based chemotherapy.

Detailed Description

      This is Phase 1b/2a, open label, multi-center study to assess safety, tolerability,
      pharmacokinetics and anti-tumor activity of vactosertib in combination with durvalumab in
      patients advanced NSCLC. This study has been designed to allow for an investigation of the
      optimal dose of vactosertib in combination with durvalumab. There are two parts to this
      study: Phase 1b, vactosertib dose-escalation study to determine the recommended phase 2 dose
      (RP2D) and Phase 2a, non-randomized parallel dose expansion study to confirm RP2D.

      In the current dose-escalation (Phase 1b) study to determine RP2D, vactosertib dosing will
      begin at 100 mg BID for 5 days per week in combination with durvalumab 1500 mg, Q4W.
      According to the following dose escalation rule, 200 mg BID oral dose as maximum administered
      dose (MAD) will be administered in combination with durvalumab.

      This phase 2a study is a study designed to evaluate the anti-tumor effects of vactosertib in
      combination with durvalumab in a total of 45 patients with PD-L1 positive advanced NSCLC who
      progressed following platinum-based chemotherapy (no prior immunotherapy)
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation of TEW-7197ExperimentalTEW-7197 will be administered orally for 5 days per week (5D/W) and Durvalumab administration.
  • TEW-7197

Eligibility Criteria

        Inclusion Criteria:

          1. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at
             enrollment

          2. Histological or cytological confirmation of advanced NSCLC who progressed following
             platinum-based chemotherapy.

          3. Confirmation of measurable disease based on RECIST 1.1 by investigators

          4. No prior exposure to immune-mediated therapy .

          5. In dose escalation phase, 6 DLT evaluable patients whose tumor cell PD-L1 expression
             less than 25% will be enrolled in each cohort. In dose expansion phase, 45 patients
             with confirmed PD-L1-positive NSCLC by the Ventana SP263 IHC assay will be enrolled

          6. All patients must be able to provide an available tumor sample taken ≤3 years prior to
             screening

          7. Adequate organ and marrow function

          8. Must have a life expectancy of at least 12 weeks

          9. Body weight >30 kg

        Exclusion Criteria:

          1. History of allogeneic organ transplantation.

          2. Active or prior documented autoimmune or inflammatory disorders

          3. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
             infection, symptomatic congestive heart failure .

          4. History of another primary malignancy

          5. History of active primary immunodeficiency

          6. Brain metastases or spinal cord compression.

          7. QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥450 ms in male
             and ≥470 ms in female

          8. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
             excipients

          9. Receipt of the last dose of anticancer therapy (chemotherapy, endocrine therapy,
             targeted therapy, biologic therapy, tumor embolization, or monoclonal antibodies) ≤ 3
             weeks prior to the first dose of study drug

         10. Radiotherapy with a limited field of radiation for palliation within 1 week of the
             first dose of study treatment

         11. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.

         12. Major surgical procedure

         13. Current or prior use of immunosuppressive medication within 14 days.

         14. The prohibited medications

         15. Participation in another clinical study with an investigational product administered
             in the last 30 days

         16. Judgment by the Investigator that the patient should not participate in the study if
             the patient is unlikely to comply with study procedures, restrictions, and
             requirements.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:4 weeks
Safety Issue:
Description:To define the MTD

Secondary Outcome Measures

Measure:Number of participants with treatment -related adverse events
Time Frame:From screening through study completion (up to 28 days after the last dose of Investigational Drug
Safety Issue:
Description:To evaluate safety profile of TEW-7197 with regards to frequency, type,grade and seriousness and causality of treatment-related clinical and laboratory adverse events
Measure:Objective Response Rate (%)
Time Frame:every 2 cycles (each cycle is 28 days) and end of treatment (EOT) time point ,EOT is defined as within 30 days from the last dose of study medication by the protocol
Safety Issue:
Description:ORR of TEW-7197 in combination with durvalumab by RECIST v1.1
Measure:Pharmacokinetics (PK) of TEW-7197
Time Frame:At cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Peak Plasma Concentration of TEW-7197
Measure:Pharmadynamics of TEW-7197
Time Frame:At cycle 1 ,3 (each cycle is 28days)
Safety Issue:
Description:Circulating cytokines including TGF-β1, PAI-1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MedPacto, Inc.

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