Clinical Trials /

A Trial of AVID200, a Transforming Growth Factor β (TGFβ) Inhibitor, in Patients Malignancies

NCT03834662

Description:

TGFβ has profound local immunosuppressive and immunoexclusion effects in the tumor microenvironment that are integrally involved in the failure of immune checkpoint inhibitors in some tumors. Preclinical data in a variety of models strongly support the study of AVID200 in patients with treatment-refractory advanced and metastatic malignancies as an approach to reducing immunosuppression/exclusion and increasing the activity of immune checkpoint inhibitors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Trial of AVID200, a Transforming Growth Factor β (TGFβ) Inhibitor, in Patients Malignancies
  • Official Title: A Phase 1 Cohort Dose-Escalation Trial of AVID200, a Transforming Growth Factor β (TGFβ) Inhibitor, in Patients With Advanced or Metastatic Solid Tumor Malignancies

Clinical Trial IDs

  • ORG STUDY ID: AVID200-03
  • NCT ID: NCT03834662

Conditions

  • Malignant Solid Tumor

Interventions

DrugSynonymsArms
AVID200TGFβ receptor ectodomain-IgG Fc fusion proteinDose Level 1: 180 mg/m2 of AVID200

Purpose

TGFβ has profound local immunosuppressive and immunoexclusion effects in the tumor microenvironment that are integrally involved in the failure of immune checkpoint inhibitors in some tumors. Preclinical data in a variety of models strongly support the study of AVID200 in patients with treatment-refractory advanced and metastatic malignancies as an approach to reducing immunosuppression/exclusion and increasing the activity of immune checkpoint inhibitors.

Detailed Description

      TGFβ inhibits local anti-tumor immunity in the tumor microenvironment (TME) and also promotes
      the epithelial to mesenchymal transition (EMT) that enhances the metastatic potential of
      tumor cells. Cancer-associated fibroblasts (CAFs) are a critical constituent of the TME. As
      is the case for fibrosis in other settings, these cells are myofibroblast-like, and respond
      to and are activated by tumor-derived TGFβ. CAFs play a critical role in promoting EMT
      resulting in increased tumor cell migration and invasion as well as maintaining the TME to
      support tumor cell survival. The immunosuppressive role of TGFβ in the TME has been clearly
      demonstrated with the activation of CAFs being an important mechanism underlying immune cell
      exclusion. Exclusion of immune cells from tumors and local immunosuppression can both be
      reversed by AVID200 therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Level 1: 180 mg/m2 of AVID200ExperimentalIntravenous infusion of AVID200 over 1 hour administered every three weeks. Starting dose for dose escalation.
  • AVID200
Dose Level 2: 550 mg/m2 of AVID200ExperimentalIntravenous infusion of AVID200 over 1 hour administered every three weeks.
  • AVID200
Dose Level 3: 1100 mg/m2ExperimentalIntravenous infusion of AVID200 over 1.5 hours administered every three weeks.
  • AVID200

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with a documented (histologically or cytologically proven) solid tumor
             malignancy that is locally advanced or metastatic

          -  Patients with a malignancy that is currently not amenable to surgical intervention due
             to either medical contraindications or non-resectability of the tumor

          -  Patients with a malignancy that is either refractory to, or the patient is intolerant
             of existing therapy(ies) known to provide clinical benefit, or for which no standard
             therapy is available

          -  Patients with measurable or non-measurable disease according to RECIST, v1.1

          -  Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of
             0 or 1 (or equivalent Karnofsky PS), and anticipated life expectancy of ≥ 3 months

          -  Patients and their partners who are either not of childbearing potential or who agree
             to use a highly effective, non-hormonal, method of contraception during the study and
             continuing until 4 months after the last dose of study drug); male patients agreeing
             to refrain from sperm donation during this period.

          -  Patients with the ability to understand and give written informed consent for
             participation

        Exclusion Criteria:

          -  Patients with an active second malignancy or history of another malignancy within the
             last 2 years with the exception of:

               -  Treated non-melanoma skin cancers

               -  Treated carcinoma in situ (CIS) of the breast, cervix, bladder, colon,
                  endometrium, skin (melanoma) provided complete response (CR) was achieved at
                  least 2 years prior to study and no additional therapy is ongoing or required
                  during study period with the exception of anti-estrogen/androgen therapy or
                  bisphosphonates

               -  Controlled, superficial carcinoma of the bladder

               -  T1a carcinoma of the prostate comprising < 5% of resected tissue and prostate
                  specific antigen (PSA) within normal limits (WNL) since resection

          -  Any antineoplastic agent for the primary malignancy (standard or investigational),
             without delayed toxicity, within 4 weeks or 5 plasma half-lives, whichever is
             shortest, prior to C1/D1 and during study with the exception of:

             -Nitrosoureas and mitomycin C within 6 weeks prior to C1/D1 and during study

          -  Any other investigational treatments within 4 weeks prior to and during study;
             includes participation in any medical device or supportive care therapeutic
             intervention trials

          -  Radiotherapy for target lesions within 4 weeks prior to C1/D1 and during study;
             radiotherapy for non-target lesions within 2 weeks prior to C1/D1

          -  Radiotherapy within 2 weeks prior to C1/D1 and during study. Patients must have
             recovered from all radiation-related toxicities, not require corticosteroids, and not
             have had radiation pneumonitis.

          -  Use of live vaccines against infectious diseases 4 weeks prior to C1/D1 and during
             study

          -  Immunosuppressive or systemic hormonal therapy (> 10 mg daily prednisone or
             equivalent) within 2 weeks prior to C1/D1 and during study

          -  Prophylactic use of hematopoietic growth factors within 2 weeks prior to C1/D1 and
             during Cycle 1 of study; thereafter prophylactic use of growth factors is allowed as
             clinically indicated
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, for up to 24 months
Safety Issue:
Description:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Formation Biologics

Trial Keywords

  • Solid tumors

Last Updated

August 28, 2019