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

NCT03834662 | Completed Phase 1 FDA Drug

• 1 other identifier: AVID200-03
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 3

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.

Conditions

Malignant Solid Tumor

Keywords

Solid tumors

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

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

  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

Study Arms (3)

Dose Level 1: 180 mg/m2 of AVID200

EXPERIMENTAL

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

Drug: AVID200

Dose Level 2: 550 mg/m2 of AVID200

EXPERIMENTAL

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

Drug: AVID200

Dose Level 3: 1100 mg/m2

EXPERIMENTAL

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

Drug: AVID200

Interventions

AVID200 DRUG

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

Also known as: TGFβ receptor ectodomain-IgG Fc fusion protein

Dose Level 1: 180 mg/m2 of AVID200; Dose Level 2: 550 mg/m2 of AVID200; Dose Level 3: 1100 mg/m2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Formation Biologics: collaborator

Study Sites (3)

START Midwest Clinic

Grand Rapids, Michigan, 49546, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Princess Margaret Cancer Centre

Toronto, M5G 1Z5, Canada

Location

Study Officials

• Paul I Nadler, MD

  Forbius (Formation Biologics)

  STUDY DIRECTOR

Study Design

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

Model Details: 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)

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: February 8, 2019
• Study Start: January 7, 2019
• Primary Completion: February 19, 2020
• Study Completion: February 19, 2020
• Last Updated: November 19, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); CA (1)