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

Running, not enrolling · Phase 2

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT05507541

Run by

Mayo Clinic

People needed

10

Starts

2023-04-19

Expected to finish

2027-07-30

Last updated by the study team

2026-04-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age >= 18 years
• Documented CD20+ mature B-cell neoplasm according to World Health Organization (WHO) classification (Swerdlow et al., 2016) as one of the following:
• Diffuse large B-cell lymphoma not otherwise specified (NOS) including
• Transformed lymphoma
• Richter's transformation
• Germinal center B-cell type
• Activated B-cell type
• High-grade B-cell lymphoma (HGBCL), NOS
• Primary mediastinal (thymic) large B-cell lymphoma
• Patients with "double-hit" or "triple-hit" diffuse large B-cell lymphoma (DLBCL) (technically as HGBCL, with MYC and BCL2 and/or BCL6 rearrangements)
• Follicular lymphoma 3B
• T-cell/histiocyte-rich large B cell lymphoma
• Large B-cell lymphoma with IRF4 rearrangement
• Primary cutaneous DLBCL, leg type
• Epstein-Barr virus (EBV) positive DLBCL, NOS
• DLBCL associated with chronic inflammation
• Intravascular large B-cell lymphoma
• ALK positive large B-cell lymphoma
• Relapsed, progressive and/or refractory disease (Cheson et al., 2007) following treatment with an anti-CD20 monoclonal antibody (e.g., rituximab) in combination with chemotherapy
• Measurable disease as defined below:
• Fluorodeoxyglucose (FDG)-avid lymphomas: Measurable disease with computerized tomography (CT) (or magnetic resonance imaging [MRI]) scan with involvement of 2 or more clearly demarcated lesions/nodes with a long axis > 1.5 cm and short axis > 1.0 cm (or 1 clearly demarcated lesion/node with a long axis > 2.0 cm and short axis >= 1.0 cm) AND FDG positron emission tomography (PET) scan that demonstrates positive lesion(s) compatible with CT (or MRI) defined anatomical tumor sites
• FDG-nonavid lymphomas: Measurable disease with CT (or MRI) scan with involvement of 2 or more clearly demarcated lesions/nodes with a long axis > 1.5 cm and short axis > 1.0 cm or 1 clearly demarcated lesion/node with a long axis > 2.0 cm and short axis >= 1.0 cm.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
• >= 4 weeks from last dose of anti-CD20 targeting therapy
• >= 12 weeks post chimeric antigen receptor (CAR) T-cell therapy

You may not qualify if…

• Primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) and, if clinically indicated, by lumbar puncture
• Known past or current malignancy other than inclusion diagnosis, except for:
• Cervical carcinoma of Stage 1B or less
• Non-invasive basal cell or squamous cell skin carcinoma
• Non-invasive, superficial bladder cancer
• Prostate cancer with a current prostate specific antigen (PSA) level < 0.1 ng/mL
• Any curable cancer with a complete response (CR) of > 2 years duration
• Received < 2 prior systemic anti-cancer therapy including investigational agents =< 4 weeks or =< 5 half-lives, whichever is shorter, prior to registration
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137) =< 4 weeks prior to registration
• Known clinically significant cardiac disease, including:
• Onset of unstable angina pectoris within 6 months of signing informed consent form (ICF)
• Acute myocardial infarction within 6 months of signing ICF
• Congestive heart failure (grade III or IV as classified by the New York Heart Association and/or known decrease ejection fraction of < 45%)
• Chronic ongoing infectious diseases (except hepatitis B or hepatitis C) requiring treatment (excluding prophylactic treatment) at the time of enrollment or =< the previous 2 weeks
• Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy or primary immunodeficiency disorder. Low-dose steroids (=< 10 mg daily of prednisone equivalent) is allowed
• Seizure disorder requiring therapy (such as steroids or anti-epileptics)
• Autologous hematopoietic stem cell transplant (HSCT) =< 100 days prior or any prior allogeneic HSCT or solid organ transplantation
• Known human immunodeficiency virus (HIV) infection
• Exposed to live or live attenuated vaccine =< 4 weeks prior to registration
• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception
• Patient has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Where it is running

• University of Iowa — Iowa City, Iowa, United States
• Mayo Clinic — Rochester, Minnesota, United States

Full record on ClinicalTrials.gov

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