GRACE: A Phase 1/2a Study of VTRU200 in Relapsed/Refractory AML, High-risk MDS, DLBCL Post CART Failure and Advanced Solid Tumors

Summary

About this study

This is the first study of VTRU200 in people. The main purpose of this study is to find a safe dose of VTRU200 and learn how the medicine behaves in the body. Researchers will also look for early signs that it may help treat cancer.

VTRU200 is an experimental immunotherapy. It is designed to help the body's immune system find and destroy cancer cells while limiting effects on healthy cells.

Unlike many cancer treatments that target a single protein, VTRU200 recognizes stress signals that are commonly found on cancer cells. These signals include certain sugars (called glycans) and fats (called phospholipids) that are present on many types of cancer cells but are uncommon on normal healthy cells. VTRU200 also attaches to immune cells called T cells and helps direct them to attack cancer cells.

Because VTRU200 targets features that are shared by many cancers, it may continue to work even if cancer cells lose or change individual proteins that other treatments depend on.

Who can take part?

This study is for people with certain blood cancers that have come back after treatment or have not responded to available treatments. These include:

Acute myeloid leukemia (AML) Higher-risk myelodysplastic syndromes (HR-MDS) Diffuse large B-cell lymphoma (DLBCL) that has returned after CAR T-cell therapy

Later parts of the study may also include adolescents and children with AML.

What will happen during the study?

Participants will receive VTRU200 through a vein (intravenous infusion).

The study will begin by giving small doses to help determine the safest dose for future participants. If those doses are well tolerated, later participants may receive higher doses.

Researchers will:

Monitor participants closely for side effects. Perform blood tests to measure how VTRU200 moves through and leaves the body. Measure how the immune system responds to treatment. Check whether the cancer shrinks, disappears, or remains under control.

Participants may receive multiple treatment cycles if they continue to benefit and do not have unacceptable side effects.

What are the possible benefits?

VTRU200 may or may not help participants. Information learned from this study may help develop new treatments for people with these cancers in the future.

What are the possible risks?

Because VTRU200 is being tested in humans for the first time, not all side effects are known.

Possible risks include reactions related to activation of the immune system, infusion-related reactions, laboratory test changes, and other side effects. Participants will be monitored closely throughout the study, and medical care will be available if side effects occur.

Brief Study Description

This first-in-human, open-label, Phase 1/2a study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of VTRU200 in participants with relapsed or refractory acute myeloid leukemia (AML), higher-risk myelodysplastic syndromes (HR-MDS), or diffuse large B-cell lymphoma (DLBCL) following CAR T-cell therapy. VTRU200 is an investigational trispecific T-cell engager that binds stress-associated glycans, phosphatidylserine, and CD3 to redirect T cells toward cancer cells. The Phase 1 dose-escalation portion will determine the recommended Phase 2 dose (RP2D), followed by disease-specific expansion cohorts to further evaluate safety and preliminary antitumor activity.

Why is this research important?

Many blood cancers eventually stop responding to available treatments. Cancer cells can escape therapy by changing or losing the proteins that many current medicines target.

VTRU200 is designed to recognize stress-related features that many cancer cells share rather than relying on a single protein target. Researchers hope this approach may reduce the chance of treatment resistance while limiting damage to healthy cells. This study will help determine whether VTRU200 can be given safely and whether it shows early signs of helping people with difficult-to-treat blood cancers.

Conditions

• Acute Myeloid Leukemia
• Diffuse Large B Cell Lymphoma (DLBCL)
• High Risk Myelodysplastic Syndrome
• Solid Tumor Malignancies
• Pediatric Acute Myeloid Leukemia

Interventions

BIOLOGICAL

VTRU200

VTRU200 is an investigational humanized trispecific T-cell engager administered by intravenous infusion. It binds CD3 on T cells and tumor associated glycans and lipids to redirect T-cell cytotoxicity toward malignant cells. Multiple dose levels will be evaluated during dose escalation to determine safety and the recommended Phase 2 dose.

Sponsors & Collaborators

• Vitruviae

  lead INDUSTRY

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

6 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-01-31

Primary Completion

2028-01-31

Completion

2029-01-31

FDA Drug

Yes