Malignant Solid Tumor
Conditions
Keywords
Solid tumors
Brief summary
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.
Interventions
DRUGAVID200
A TGFβ receptor ectodomain-IgG Fc fusion protein inhibitor of TGFβ
Sponsors
Formation Biologics
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | 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 | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
Countries
Canada, United States
Outcome results
None listed