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Vactosertib in Combination With Pembrolizumab in Metastatic Colorectal or Gastric Cancer

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: NCT03724851
Recruitment Status : Recruiting
First Posted : October 30, 2018
Last Update Posted : July 10, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
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 pembrolizumab in patients with metastatic or locally advanced colorectal or gastric/gastroesophageal junction adenocarcinoma

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Gastric Cancer Gastroesophageal Junction Adenocarcinoma 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 pembrolizumab in patients with mCRC including CMS4 or diffuse GC/GEJC with two phases (Dose Finding Phase and Dose Expansion Phase). At screening, CMS4 will be classified by an experienced pathologist in the central lab that will examine the histology of primary surgical tissues. Approximately, 67 total patients are expected to be enrolled in this study. The first phase of the study, the Dose Finding Phase, will determine the MTD of the combination regimen. The second phase, the Dose Expansion Phase, will further evaluate the combination regimen to confirm RP2D.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 67 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2a Study to Assess the Safety, Tolerability, PK, and Antitumor Activity of Vactosertib in Combination With Pembrolizumab in Patients With Metastatic Colorectal or Gastric Gastroesophageal Junction Adenocarcinoma
Actual Study Start Date : November 28, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation of TEW-7197
TEW-7197 will be administered orally for 5 days per week (5D/W) and Pembrolizumab will be administered as a dose of 200 mg every 3weeks.
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.Pembrolizumab will be administered as a dose of 200 mg every 3weeks.
Other Name: vactosertib




Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 3weeks ]
    To define the MTD


Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events assessed by NCI CTCAE v 5.0 [ 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. Efficacy of TEW-7197+Pembrolizumab [ Time Frame: through study completion, an average of 2 years ]
    Objective Response Rate(%)

  3. Pharmacokinetics (PK) of TEW-7197 [ Time Frame: At cycle 1(each cycle is 21days) ]
    Peak Plasma Concentration of TEW-7197

  4. Pharmacodynamics of TEW-7197 [ Time Frame: At cycle 1 ,3 (each cycle is 21days) ]
    pSMAD in peripheral blood mononuclear cell determined by immunohistochemistry



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. WHO / ECOG /PS of 0 or 1 at enrollment
  2. Must have a life expectancy of at least 12 weeks
  3. Patients with histologically or cytologically confirmed advanced or metastatic colorectal cancer who have disease progression after treatment with all available therapies including fluoropyrimidine and oxaliplatin or irinotecan for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment.
  4. Histologically- or cytologically- confirmed, advanced or metastatic diffuse-type adenocarcinoma of the stomach or gastroesophageal (GE) junction who have had disease progression after at least two previous courses of chemotherapy for metastatic disease, which should include fluoropyrimidine and platinum.
  5. Confirmation of measurable disease based on RECIST 1.1
  6. ICI-naïve patients
  7. Adequate organ and marrow function as defined below: Bilirubin≤1.5 ×ULN ,AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for patients with liver metastases) ,INR OR PT ≤1.5 × ULN , ANC ≥1500/µL , Platelets ≥100 000/µL, Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L1, Creatinine ≤1.5 × ULN

Exclusion Criteria:

  1. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
  2. Has received prior radiotherapy within 2 weeks of start of study treatment.
  3. Has received a live vaccine within 30 days prior to the first dose of study drug
  4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
  5. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
  6. Has known CNS metastases and/or leptomeningeal involvement
  7. Judgement by the investigator that the patient should not participate in the study .

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): NCT03724851


Contacts
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Contact: Kyounghee Kim, BSN 82-70-8610-2591 kyounghee.kim@medpacto.com

Locations
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Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Sponsors and Collaborators
MedPacto, Inc.
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Sunjin Hwang, MD MedPacto, Inc.
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Responsible Party: MedPacto, Inc.
ClinicalTrials.gov Identifier: NCT03724851    
Other Study ID Numbers: MP-VAC-204
Mk3475 Keynote 900 ( Other Identifier: MSD )
First Posted: October 30, 2018    Key Record Dates
Last Update Posted: July 10, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases