TTI-622 in Combination With Pembrolizumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Summary

This phase II trial tests the safety, side effects, and best dose of TTI-621 (closed to enrollment) or TTI-622 in combination with pembrolizumab in treating patients with diffuse large B-cell lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). TTI-621 and TTI-622 are called fusion proteins. A fusion protein includes two specialized proteins that are joined together. In TTI-621 and TTI-622, one of the proteins binds with other proteins found on the surface of certain cells that are part of the immune system. The other protein targets and blocks a protein called CD47. CD47 is present on cancer cells and is used by those cells to hide from the body's immune system. By blocking CD47, TTI-621 and TTI-622 may help the immune system find and destroy cancer cells. Pembrolizumab is a monoclonal antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) that works by helping the body\'s immune system attack the cancer and may interfere with the ability of cancer cells to grow and spread. Giving TTI-621 (closed to enrollment) or TTI-622 in combination with pembrolizumab may kill more cancer cells in patients with relapsed or refractory diffuse large B-cell lymphoma.

Conditions

• Recurrent ALK Positive Large B-Cell Lymphoma
• Recurrent B-Cell Non-Hodgkin Lymphoma
• Recurrent Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation
• Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Recurrent EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Recurrent Grade 3b Follicular Lymphoma
• Recurrent High Grade B-Cell Lymphoma
• Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
• Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
• Recurrent High Grade B-Cell Lymphoma, Not Otherwise Specified
• Recurrent Intravascular Large B-Cell Lymphoma
• Recurrent Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type
• Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma
• Recurrent T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
• Refractory ALK Positive Large B-Cell Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation
• Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Refractory EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Refractory Grade 3b Follicular Lymphoma
• Refractory High Grade B-Cell Lymphoma
• Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
• Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
• Refractory High Grade B-Cell Lymphoma, Not Otherwise Specified
• Refractory Intravascular Large B-Cell Lymphoma
• Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type
• Refractory Primary Mediastinal Large B-Cell Lymphoma
• Refractory T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
• Recurrent Gray Zone Lymphoma

Interventions

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Computed Tomography

Undergo PET/CT or CT scan

DRUG

Ontorpacept

Given IV

BIOLOGICAL

Pembrolizumab

Given IV

PROCEDURE

Positron Emission Tomography

Undergo PET/CT scans

DRUG

Maplirpacept

Given IV

PROCEDURE

Biopsy

Undergo tumor biopsy

Sponsors & Collaborators

• Mayo Clinic

  lead OTHER

Principal Investigators

• Stephen M. Ansell, MD, PhD · Mayo Clinic in Rochester

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-04-19

Primary Completion

2027-07-30

Completion

2027-07-30

FDA Drug

Yes

Countries

• United States

Study Locations