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Vactosertib in Combination With Pembrolizumab in Metastatic Colorectal or Gastric Cancer

Primary Purpose

Metastatic Colorectal Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma

Status

Unknown status

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

TEW-7197

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

WHO / ECOG /PS of 0 or 1 at enrollment
Must have a life expectancy of at least 12 weeks
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.
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.
Confirmation of measurable disease based on RECIST 1.1
ICI-naïve patients
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:

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
Has received prior radiotherapy within 2 weeks of start of study treatment.
Has received a live vaccine within 30 days prior to the first dose of study drug
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Has known CNS metastases and/or leptomeningeal involvement
Judgement by the investigator that the patient should not participate in the study .

Sites / Locations

Asan Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose Escalation of TEW-7197

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose

To define the MTD

Secondary Outcome Measures

Number of participants with treatment-related adverse events assessed by NCI CTCAE v 5.0

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.

Efficacy of TEW-7197+Pembrolizumab

Objective Response Rate(%)

Pharmacokinetics (PK) of TEW-7197

Peak Plasma Concentration of TEW-7197

Pharmacodynamics of TEW-7197

pSMAD in peripheral blood mononuclear cell determined by immunohistochemistry

Full Information

NCT ID

NCT03724851

First Posted

October 10, 2018

Last Updated

September 22, 2021

Sponsor

MedPacto, Inc.

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT03724851

Brief Title

Vactosertib in Combination With Pembrolizumab in Metastatic Colorectal or Gastric Cancer

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Unknown status

Study Start Date

November 28, 2018 (Actual)

Primary Completion Date

June 10, 2021 (Actual)

Study Completion Date

August 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MedPacto, Inc.

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Colorectal Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

67 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dose Escalation of TEW-7197

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

TEW-7197

Other Intervention Name(s)

vactosertib

Intervention Description

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.

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose

Description

To define the MTD

Time Frame

3weeks

Secondary Outcome Measure Information:

Title

Number of participants with treatment-related adverse events assessed by NCI CTCAE v 5.0

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.

Time Frame

From screening through study completion (up to 28 days after the last dose of Investigational Drug)

Title

Efficacy of TEW-7197+Pembrolizumab

Description

Objective Response Rate(%)

Time Frame

through study completion, an average of 2 years

Title

Pharmacokinetics (PK) of TEW-7197

Description

Peak Plasma Concentration of TEW-7197

Time Frame

At cycle 1(each cycle is 21days)

Title

Pharmacodynamics of TEW-7197

Description

pSMAD in peripheral blood mononuclear cell determined by immunohistochemistry

Time Frame

At cycle 1 ,3 (each cycle is 21days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: WHO / ECOG /PS of 0 or 1 at enrollment Must have a life expectancy of at least 12 weeks 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. 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. Confirmation of measurable disease based on RECIST 1.1 ICI-naïve patients 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: 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 Has received prior radiotherapy within 2 weeks of start of study treatment. Has received a live vaccine within 30 days prior to the first dose of study drug Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Has known CNS metastases and/or leptomeningeal involvement Judgement by the investigator that the patient should not participate in the study .

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sunjin Hwang, MD

Organizational Affiliation

MedPacto, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Asan Medical Center

City

Seoul

ZIP/Postal Code

05505

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Vactosertib in Combination With Pembrolizumab in Metastatic Colorectal or Gastric Cancer

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