Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Vactosertib in Combination With Durvalumab in Advanced NSCLC

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: NCT03732274
Recruitment Status : Recruiting
First Posted : November 6, 2018
Last Update Posted : January 18, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
MedPacto, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Metastatic Drug: TEW-7197 Phase 1 Phase 2

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)

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 21, 2018
Estimated Primary Completion Date : October 1, 2022
Estimated Study Completion Date : December 30, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Dose Escalation of TEW-7197
TEW-7197 will be administered orally for 5 days per week (5D/W) and Durvalumab administration.
Drug: TEW-7197
TEW-7197 will be administered orally for 5 days per week (5D/W) at the same time in the morning and evening (BID) approximately 12 hours apart. Durvalumab will be administered as a dose of 1500 mg every 4weeks.
Other Name: vactosetib




Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 4 weeks ]
    To define the MTD


Secondary Outcome Measures :
  1. 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 ]
    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

  2. 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 ]
    ORR of TEW-7197 in combination with durvalumab by RECIST v1.1

  3. Pharmacokinetics (PK) of TEW-7197 [ Time Frame: At cycle 1 (each cycle is 28 days) ]
    Peak Plasma Concentration of TEW-7197

  4. Pharmadynamics of TEW-7197 [ Time Frame: At cycle 1 ,3 (each cycle is 28days) ]
    Circulating cytokines including TGF-β1, PAI-1



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:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT03732274


Contacts
Layout table for location contacts
Contact: Kyounghee Kim, BSN 82-70-8610-2591 kyounghee.kim@medpacto.com
Contact: Sunjin Hwang, MD 82-70-8610-2597 sunjin.hwang@medpacto.com

Locations
Layout table for location information
Korea, Republic of
Yeonsei University Hospotal Recruiting
Seoul, Korea, Republic of
Contact: Byoung Chul Cho, PHD    82-10-5212-8867    CBC1971@yuhs.ac   
Sponsors and Collaborators
MedPacto, Inc.
AstraZeneca
Investigators
Layout table for investigator information
Study Director: Sunjin Hwang, MD MedPacto, Inc.
Layout table for additonal information
Responsible Party: MedPacto, Inc.
ClinicalTrials.gov Identifier: NCT03732274    
Other Study ID Numbers: MP-VAC-203
First Posted: November 6, 2018    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms