Vactosertib in Combination With Pembrolizumab in Metastatic Colorectal or Gastric Cancer
Study Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| 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.
Study Design
Arms and Interventions
| 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 Names:
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Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose [3weeks]
To define the MTD
Secondary Outcome Measures
- Number of participants with treatment-related adverse events assessed by NCI CTCAE v 5.0 [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.
- Efficacy of TEW-7197+Pembrolizumab [through study completion, an average of 2 years]
Objective Response Rate(%)
- Pharmacokinetics (PK) of TEW-7197 [At cycle 1(each cycle is 21days)]
Peak Plasma Concentration of TEW-7197
- Pharmacodynamics of TEW-7197 [At cycle 1 ,3 (each cycle is 21days)]
pSMAD in peripheral blood mononuclear cell determined by immunohistochemistry
Eligibility Criteria
Criteria
Inclusion Criteria:
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WHO / ECOG /PS of 0 or 1 at enrollment
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Must have a life expectancy of at least 12 weeks
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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.
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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.
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Confirmation of measurable disease based on RECIST 1.1
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ICI-naïve patients
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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:
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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
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Has received prior radiotherapy within 2 weeks of start of study treatment.
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Has received a live vaccine within 30 days prior to the first dose of study drug
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Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
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Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
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Has known CNS metastases and/or leptomeningeal involvement
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Judgement by the investigator that the patient should not participate in the study .
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Asan Medical Center | Seoul | Korea, Republic of | 05505 |
Sponsors and Collaborators
- MedPacto, Inc.
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Sunjin Hwang, MD, MedPacto, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MP-VAC-204
- Mk3475 Keynote 900