A Phase 1 Study of AMV564 in Patients With Intermediate or High-Risk Myelodysplastic Syndromes

A Phase 1, Multicenter, Open Label Study of AMV564, a Bispecific CD33/CD3 T-cell Engager, in Patients With Intermediate or High-Risk Myelodysplastic Syndromes

An open label, Phase 1, study of AMV564 as monotherapy to assess the safety and efficacy in patients with Myelodysplastic Syndromes

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome (MDS)
• Intervention / Treatment: Drug: AMV564 14-Day CIV

Detailed Description

A dose-escalation with expansion study of AMV564 (T cell engager) as monotherapy in patients with intermediate-2 or high-risk Myelodysplastic Syndromes

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University, Siteman Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 42310
      • Ohio State University Comprehensive Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 years of age
• Diagnosis of MDS according to WHO 2016 criteria
• ECOG performance status of 0 or 1
• Intermediate-2 or high-risk disease per IPSS
• Fewer than 20% blasts in the bone marrow or peripheral blood
• Disease that is refractory to or relapsed from either a hypomethylating agent (e.g. decitabine or azacitidine) or a standard AML-type intensive regimen
• Adequate organ function
• Prior allogeneic transplant performed ≥ 3 months prior to first dose of AMV564 is allowed provided there is no evidence of active graft-versus-host disease (GVHD) and the patient has been off immunosuppressive therapy for ≥ 4 weeks.

Exclusion Criteria:

• History of, or known, central nervous system (CNS) disease involvement, or prior history of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade ≥ 3 drug-related CNS toxicity
• Prior allogeneic transplant if performed < 3 months prior to first dose of AMV564, if patient has active GVHD, or if patient has not been off immunosuppressive
• Prior treatment with a therapeutic agent targeting CD33 (e.g. gemtuzumab ozogamicin, SGN-CD33A or AMG 330).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (3+3 design); A 3 + 3 design, with dose-escalation of AMV564, up to a Maximum Tolerated Dose (MTD) level. AMV564 will be tested as a 14-Day CIV regimen (14-Day Continuous Intravenous Infusion Regimen).	Drug: AMV564 14-Day CIV; A 14-Day Continuous Intravenous Infusion regimen
Experimental: Dose Expansion; Following determination of the MTD of AMV564, the study will expand at the MTD or a dose level lower than the MTD to obtain initial estimates of response rates and additional information on safety.	Drug: AMV564 14-Day CIV; A 14-Day Continuous Intravenous Infusion regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (Dose Escalation)	Dose limiting toxicity to be measured by AEs and SAEs by dose level	DLTs will be evaluated through 28 days for the 14-Day Continuous Intravenous Infusion Infusion regimen, and 35 days for the Intermittent Intravenous Dosing regimen
Overall Response Rate (Dose Expansion)	Overall response rate (ORR), defined as the proportion of patients who achieve a CR, marrow CR or PR by IWG criteria. Point estimates for ORR, along with the approximate lower 1-sided 90% confidence intervals, will be calculated.	The treatment period will extend from initiation of AMV564 treatment until the Safety Follow Up visit (30 days after the end of infusion), or response assessment of the last induction cycle, whichever occurs later.

Collaborators and Investigators

• Sponsor: Amphivena Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2018
• Primary Completion (Actual): July 31, 2020
• Study Completion (Actual): July 31, 2020

Study Registration Dates

• First Submitted: April 24, 2018
• First Submitted That Met QC Criteria: April 24, 2018
• First Posted (Actual): May 4, 2018

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: AMV564-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No