TTI-622 in Combination With Pembrolizumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Phase 2 Study With Safety run-in of PD-1 Inhibitor and IgG4 SIRPα-Fc Fusion Protein (TTI-622) in Relapsed Diffuse Large B-Cell Lymphoma (DLBCL)
2 other identifiers
interventional
10
1 country
2
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Apr 2023
Typical duration for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 17, 2022
CompletedFirst Posted
Study publicly available on registry
August 19, 2022
CompletedStudy Start
First participant enrolled
April 19, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 30, 2027
April 22, 2026
April 1, 2026
4.3 years
August 17, 2022
April 20, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Recommended phase 2 dose of maplirpacept (TTI-622) when given in combination with pembrolizumab (Safety run-in)
Defined as the highest dose for which at most 1 out of 6 subjects experience significant toxicity during the 6-week safety assessment period. Toxicity will be measured per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5. Significant toxicity is defined as an adverse event occurring during the first cycle of treatment that is possibly, probably, or definitely related to study treatment.
Up to 6 weeks
Overall response (Phase 2)
A success is defined as an objective status of partial metabolic response (PMR) or complete metabolic response (CMR) by positron emission tomography-computed tomography (PET-CT) based criteria at any time. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Note: For patients where PET/CT scan was not available due to insurance coverage and who received a CT scan only, they will still be considered evaluable for the primary endpoint and will be included in the denominator for estimating overall response rate. In these patients, the CT-based responses will be reported descriptively.
Up to 2 years
Secondary Outcomes (4)
Duration of response (DOR) (Phase 2)
Up to 2 years
Incidence of adverse events (AEs) (Phase 2)
Up to 2 years
Overall survival (OS) (Phase 2)
up to 2 years
Progression-free survival (PFS) (Phase 2)
Up to 2 years
Study Arms (2)
Arm A (pembrolizumab, TTI-621) -- CLOSED TO ACCRUAL 8/16/2024
EXPERIMENTALPatients receive pembrolizumab IV over 30 minutes on day 1 of each cycle and TTI-621 IV over 60-120 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT scans or CT scans of the chest, abdomen, and pelvis prior to cycle 3 and every 4 cycles thereafter. If no disease progression after cycle 12, patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle and TTI-621 IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 23 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and/or CT and blood sample collection throughout the study. Patients may undergo biopsy on study.
Arm B (pembrolizumab, TTI-622)
EXPERIMENTALPatients receive pembrolizumab IV over 30 minutes on day 1 of each cycle and TTI-622 IV over 60-90 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT scans or CT scans of the chest, abdomen, and pelvis prior to cycle 3 and every 4 cycles thereafter. If no disease progression after cycle 12, patients then receive pembrolizumab IV over 30 minutes on days 1 of each cycle and TTI-622 IV over 60-90 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 23 cycles in the absence of disease progression or unacceptable toxicity.
Interventions
Undergo blood sample collection
Undergo PET/CT or CT scan
Given IV
Given IV
Undergo PET/CT scans
Given IV
Undergo tumor biopsy
Eligibility Criteria
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
- +26 more criteria
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
- 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)
- +32 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (2)
University of Iowa
Iowa City, Iowa, 52242, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Stephen M. Ansell, MD, PhD
Mayo Clinic in Rochester
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 17, 2022
First Posted
August 19, 2022
Study Start
April 19, 2023
Primary Completion (Estimated)
July 30, 2027
Study Completion (Estimated)
July 30, 2027
Last Updated
April 22, 2026
Record last verified: 2026-04