Vactosertib in Combination with Pembrolizumab in Metastatic Colorectal or Gastric Cancer

NCT03724851 | Completed Phase 1

• 2 other identifiers: MP-VAC-204Mk3475 Keynote 900
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 5

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

Conditions

Metastatic Colorectal Cancer; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose

  Incidence of nature of DLTs

  approximately 2 years

• Safety and Tolerability

  Incidence, nature and severity of adverse events (AEs) graded according to NCI CTCAE v5.0

  approximately 2 years

Secondary Outcomes (3)

• Efficacy 1

  approximately 2 years

• Efficacy 2

  approximately 2 years

• Efficacy 3

  up to 3 years

Study Arms (3)

Dose Expansion (300mg BID)

EXPERIMENTAL

TEW-7197 300mg BID, 5D/W + Pembrolizumab 200mg Q3W (n= 30)

Drug: TEW-7197

Dose Expansion (200mg BID)

EXPERIMENTAL

TEW-7197 200mg BID, 5D/W + Pembrolizumab 200mg Q3W (n= 30)

Drug: TEW-7197

Dose Expansion (200mg QD)

EXPERIMENTAL

TEW-7197 200mg QD, 5D/W + Pembrolizumab 200mg Q3W (n= 30)

Drug: TEW-7197

Interventions

TEW-7197 DRUG

Vactosertib will be administered orally without regard to meals for 5 days per week (5D/W) at the same time in the morning (QD), at the same time in the morning and evening (BID) approximately 12 hours apart. Pembrolizumab will be administered as a dose of 200 mg using a 30-minute IV infusion. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible.

Also known as: vactosertib

Dose Expansion (200mg BID); Dose Expansion (200mg QD); Dose Expansion (300mg BID)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female Age ≥19 years at the time of screening
• Patients must be able to swallow tablets and absorb vactosertib.
• \[Diagnosis/Condition for Entry into the Trial\]
• World Health Organization (WHO) / Eastern Cooperative Oncology Group (ECOG) performance status (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 non microsatellite instability high (MSI-H)/mismatch repair deficiency (dMMR) 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.
• Patients with 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 by investigators at Screening will be used to determine patient eligibility and imaging shows at least 1 lesion that is appropriate for selection as a target lesion per RECIST 1.1 is required prior to patient treatment. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to C1D1.
• All patients enrolled must be ICI-naïve patients defined as no prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
• All patients must be able to provide a newly acquired tumor biopsy during screening (preferred) or provide an available archived tumor sample. Tumor lesions used for newly acquired biopsies should not be target lesions, unless there are no other lesions suitable for biopsy, and in this instance only core needle (not excisional/incisional) biopsy is allowed.
• Patients must provide consent for an additional biopsy on C2D3-6 or C2D10-13. Post-treatment biopsy must be obtained from the same organ site as pre-treatment biopsy, if feasible, to avoid introduction of heterogeneity related to the site of tumor or metastasis. If submitting unstained cut slides, freshly cut slides should be submitted to the testing laboratory within 20 days from when the slides are cut. See Study Manual for an explanation.
• Have adequate organ function as defined in the following Table 3.

You may not qualify if:

• A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 7 days prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
• Prior/Concurrent Clinical Study Experience
• \. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Prior/Concomitant Therapy
• 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 (e.g., CTLA-4, OX 40, CD137) Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not 49 have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• The prohibited medications when using vactosertib are following (Refer to Appendix E). A minimal washout period of 5 half-lives for the following drugs is recommended prior to the first dosing.
• Medical conditions
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, \[additional examples can be added if important to the study such as transitional cell carcinoma of urothelial cancer\], or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known CNS metastases and/or leptomeningeal involvement
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab or vactosertib and/or any of its excipients

Sponsors & Collaborators

• MedPacto, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

National Cancer Center

Goyang, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Yeonsei University Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms

Interventions

vactosertib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases

Study Officials

• Minkyu Heo

  MedPacto, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2018
• First Posted: October 30, 2018
• Study Start: December 20, 2018
• Primary Completion: May 7, 2024
• Study Completion: May 7, 2024
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (5)