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Intravenous infusion of AVID200 over 1 hour administered every three weeks. Starting dose for dose escalation.

Intravenous infusion of AVID200 over 1 hour administered every three weeks.

Intravenous infusion of AVID200 over 1.5 hours administered every three weeks.

A TGFβ receptor ectodomain-IgG Fc fusion protein inhibitor of TGFβ

AVID200

Paul I Nadler, MD

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.

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.

Evaluation of the safety, tolerability, and dose-limiting toxicities (DLTs), to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of AVID200 when administered once every 3 weeks (Q3W) by IV infusion to patient cohorts (3)

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

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

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Formation Biologics

Symptoms and General Pathology

Blood and Lymph Conditions

Neoplasms

Heart and Blood Diseases

Fibrosis

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Splenomegaly

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

intravenous in dose cohorts of 70mg/m2 or 180 mg/m2

John Mascarenhas, MD

Ruben Mesa, MD

Ronald Hoffman, MD

Increased levels of TGF-β1 were detected in serum, plasma and BM and positively correlated with both grade of BMF and extent of leukemic cell infiltration in the marrow. TGF-β likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. AVID200 is a drug that targets TGF-β1 and TGF-β3. The study team hypothesizes that inhibiting the TGF-β signaling pathway in MF will decrease the fibrogenic stimuli leading to myelofibrosis and concomitantly interrupt myeloproliferation and restore normal hematopoiesis.

This is a first in human, open-label, multicenter, Phase I/Ib trial of AVID200. Patients must have intermediate-2 or higher primary myelofibrosis (PMF), post-essential thrombocythemia or polycythemia-vera related MF (Post ET/PV MF). This study will enroll up to 24 patients. AVID200 is delivered by IV infusion on day 1 of each 3 week cycle.

This is a first in human, open-label, multicenter, Phase I/Ib trial of AVID200. To date, there is no therapy for MF evaluated in the clinic that clearly demonstrates the ability to target the malignant HSC and result in effective and reproducible bone marrow morphologic, cytogenetic and molecular responses. Medicinal therapies that result in disease course modification are urgently needed in this chronic and progressive myeloid malignancy. TGF-β likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. The study team proposes that inhibiting the TGF-β signaling pathway in MF will decrease the fibrogenic stimuli leading to myelofibrosis and concomitantly interrupt myeloproliferation and restore normal hematopoiesis. AVID200 is a fusion protein containing TGF-β receptor ectodomains fused to a human Fc IgG domain. AVID200 is a potent TGFβ trap with antibody-like properties which has pM potency against two of the three TGFβ ligands, TGFβ1 and β3.

MPN-RC 118 AVID200 in Myelofibrosis

Phase I Study of AVID200 in Patients With Myelofibrosis (Myeloproliferative Neoplasms Research Consortium [MPN-RC] 118)

Cohorts of 3 patients with a maximum evaluable sample size of 12 patients and a target toxicity rate of 30% to estimate the MTD. Each cycle is 21 days.

Subjects attaining at least a CI (clinical improvement) by IWG/ELN criteria, or a decrease in bone marrow fibrosis by ≥1 grade with otherwise stable disease, will be allowed to continue AVID200 in the extension phase of the trial.

response by IWG/ELN criteria at the end of Cycle 6 and Cycle 12. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission

bone marrow fibrosis grade at the end of Cycle 6 and 12. Bone marrow fibrosis (MF) is graded as MF-0 to MF-3, with higher number indicating more disease.

MF-SAFv4.0,each of the items are scored 0 to 10, with total summation from 0 to 100, with higher score indicating more symptoms.

EORTC QLQ-C30, 28 item scored from 1 (not at all) to 4 (very much), and 2 items scored 1 (very poor) to 7 (excellent). Total score from 28 - 126, with higher score indicating poorer health

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Trial of AVID200, a Transforming Growth Factor β (TGFβ) Inhibitor, in Patients Malignancies	NCT03834662	Malignant Solid...	AVID200	18 Years -	Formation Biologics
MPN-RC 118 AVID200 in Myelofibrosis	NCT03895112	Primary Myelofi... Post-essential ... Post-polycythem... Post ET MF Post PV MF	AVID200	18 Years -	Icahn School of Medicine at Mount Sinai
A Trial of AVID200, a Transforming Growth Factor β (TGFβ) Inhibitor, in Patients Malignancies	NCT03834662	Malignant Solid...	AVID200	18 Years -	Formation Biologics

Spots Global Cancer Trial Database for avid200

Every month we try and update this database with for avid200 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for avid200

Every month we try and update this database with for avid200 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for avid200 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.