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Diffuse Large B Cell LymphomaPhase 1NCT06290622

PD-1, LAG-3 and TIM-3 Checkpoint Blockade in DLBCL

A Phase 1 study testing Retifanlimab, INCAGN02385, INCAGN02390 in people with Diffuse Large B Cell Lymphoma and Lymphoma, B-Cell, run by University of Alabama at Birmingham.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This study is investigating the optimal dose and the advantage in combining investigational immunotherapy drugs known as Retifanlimab, INCAGN02385 and INCAGN02390 to improve the responses to CAR T-cell therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Retifanlimab, INCAGN02385, INCAGN02390
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
30 Aug 2024to 31 Jan 2028
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients who have received CAR T-cell therapy within 120 days as per the United States Food and Drug Agency (USFDA) approved indications for
  • Diffuse large B-cell lymphoma (DLBCL),
  • Primary mediastinal large B-cell lymphoma (PMBCL),
  • High grade B-cell lymphoma,
  • DLBCL arising from indolent lymphoma.
  • Follicular Lymphoma Grade 3B.
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  • Who receieved a CD19 directed CAR T-cell therapy product of any of the following
  • Axicabtagene Ciloleucel (Axi-cel)
  • Tisagenlecleucel (Tisa-cel)
  • Lisocabtagene Ciloleucel (Liso-cel)
  • Patients with persistent or refractory disease with a Deauville score of 4 or 5 as per Lugano Criteria or early relapse within 90 days after CAR T-cell therapy.
  • Adequate organ function as defined below unless attributed to disease involvement.
  • liver function (bilirubin < 2mg/dL, AST and/or ALT <3 x ULN)
  • kidney function (crcl > 30ml/min using Cockroft-Gault, based on actual weight).
  • ANC ≥ 1,000/µL, Hgb > 8, Platelet Count ≥ 50,000/ µL. Transfusions allowed. Growth factor support allowed.
  • TnT or TnI < 2 × Institutional ULN. Participants with TnT or TnI levels between > 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤ 1 × ULN.
  • Patients with HIV can be included if they are on appropriate antiretroviral therapy, a CD4+ T-cell counts ≥ 300 cells/µL and no detectable viral load.
  • Age ≥ 18 years of age.
  • Eastern Cooperative Group performance (ECOG) status of 0 to 2.
  • A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
  • For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 6 months after infusion of study drug.
  • For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
  • Willing and able to participate in all required evaluations and procedures in this study protocol including receiving intravenous administration of investigational product and being admitted, when required, for at least 24 hours during investigational product administration.

Who cannot join

  • Patients who experienced Grade 3 or higher Cytokine release syndrome (CRS) or Immune cell associated neurotoxicity syndrome (ICANS) with CAR T-cell therapy as per ASTCT criteria.
  • Patients with ongoing CRS or ICANS.
  • Patients who experienced hemophagocytic lymphohistiocytosis (HLH) due to CAR T- cell therapy.
  • Prior allogeneic stem cell transplant within 6 months. The patient should not have any active Graft vs. Host disease (GVH) or should be on immune suppressive agents.
  • Prior treatment with PD-(L)1, TIM-3 or LAG-3 blocking therapy.
  • Any active, concurrent, significant illness or disease (other underlying lymphoma) or clinically significant findings including psychiatric and behavioral problems, medical history and/or physical examination findings that would preclude the patient from participation in the study such as:
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  • active infection requiring systemic therapy ≤14 days before the first dose of study drug
  • unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association [NYHA] II, III, IV;), myocardial infarction ≤6 months prior to first study drug, uncontrolled cardiac arrhythmia e.g., atrial fibrillation/flutter, cerebrovascular accidents ≤6 months before first dose of study drug
  • Significant (as defined by study doctor) pulmonary disease or disorder, including interstitial lung disease or history of interstitial lung disease, or active, noninfectious pneumonitis.
  • Severe autoimmune disorder with evidence of significant organ damage from autoimmune disorder as defined by study physician.
  • any severe or uncontrolled other disease or condition which might increase the risk associated with study participation.
  • History of myocarditis as defined by a cardiologist requiring immunosuppressive therapies.
  • Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath) and not related to underlying lymphoma.
  • Vaccination with live, attenuated vaccines within 28 days prior to the first dose of study medication.
  • Patients who develop COVID-19 (SARS-CoV2) infection at any time during screening, should not be enrolled until a negative PCR is confirmed and all clinical symptoms (as applicable) have resolved.
  • Receiving systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents). The use of inhaled corticosteroids is permitted.
  • Corticosteroids ≥ 10 mg of prednisone within 7 days of first dose of study drug.
  • Notes:
  • Physiologic corticosteroid replacement therapy at doses > 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.
  • Participants with a condition (eg, asthma or COPD) that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate.
  • Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate.
  • Brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy) or study treatment-related standard premedication are permitted.
  • Has known active HBV or HCV infection, or risk of reactivation of HBV or HCV, defined as follows (testing must be performed to determine eligibility):
  • Active HBV infection is defined by positive HBsAg and positive total anti-HBc results.
  • Note: When HBsAg is negative AND HBcAb and/or HBsAb is positive, HBV-DNA should be measured. When HBV-DNA is negative, this participant could be enrolled with close monitoring of HBV activities.
  • Active HCV is defined as a positive HCV antibody result and quantitative HCV-RNA results greater than the lower limits of detection of the assay.
  • Note: Participants positive for HCV antibody will be eligible if they are negative for HCV-RNA. Participants who have had definitive treatment for HCV are permitted if HCV RNA is undetectable.
  • Patients with prior solid organ transplant
  • Breastfeeding or pregnant
  • Any other malignancy known to be active, with the exception of
  • 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 PSA level < 0.1 ng/mL
  • Any curable or localized cancer with a CR of > 2 years' duration.
  • Known allergy or hypersensitivity to any component of either retifanlimab, INCAGN02385, or INCAGN02390 study drug formulation (including excipients and additives). Patients with known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures such as antihistamines and/or corticosteroids will also be excluded.

About this study

Official title: PD-1, LAG-3 and TIM-3 Checkpoint Blockade in DLBCL Post Chimeric Antigen Receptor T-cEll Therapy fAilUre (PLATEAU Study)

This study is investigating the optimal dose and the advantage in combining investigational immunotherapy drugs known as Retifanlimab, INCAGN02385 and INCAGN02390 to improve the responses to CAR T-cell therapy. Additionally, the study will investigate that triple checkpoint blockade of PD-1, TIM-3 and LAG-3 molecules will overcome CAR T-cell therapy resistance in patients with suboptimal responses.

Being tested
Retifanlimab, INCAGN02385, INCAGN02390
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Retifanlimab, INCAGN02385, INCAGN02390Drug

    Treatment:

    Retifanlimab -infused over 60 minutes for C1D1 followed by a 60-minute observation period. If no infusion related reactions are observed infusion may be reduced to 30 minutes and no further observation period is needed for future cycles. If there is a reaction continue with 60 minute infusion and observation period for following cycle. Retifanlimab should always be administered first.

    INCAGN02385 and INCAGN02390 -individually administered over 30 minutes one after another. For first infusions of retifanlimab, INCAGN02385 and INCAGN02390, a 4 hour observation period is necessary after completion of all infusion. If no infusion related reactions are observed, for subsequent infusions no further observation period is needed for future cycles.

Study groups in NCT06290622
Study groupRoleWhat they receive
Dose Level AssignmentsExperimentalDose Level 1 Retifanlimab 375mg INCAGN02385 250mg INCAGN02390 200mg Dose Level 2 Retifanlimab 500mg INCAGN02385 250mg INCAGN02390 200mg Dose Level 3 Retifanlimab 750mg INCAGN02385 250mg INCAGN02390 200mg
Receives: Drug: Retifanlimab, INCAGN02385, INCAGN02390

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Identify the optimal biological dose (OBD) for Retifanlimab in combination with INCAGN02385 and INCAGN02390 in relapsed/refractory DLBCL.

    To find the dose at which efficacy and toxicity are balanced to obtain a desirable dose.

    Measured: 12 and 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2024
  2. Study start30 Aug 2024 (estimated)
  3. Primary completion30 Jun 2026 (estimated)
  4. Study completion31 Jan 2028 (estimated)

Why it stopped: Investigator request to no longer pursue this study. Lack of support from drug company. This trial never opened. Withdrew IND.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06290622
Sponsor's protocol ID
IRB300012414 (UAB23136)
Status last verified
May 2025
First submitted
26 Feb 2024
Last updated
6 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Retifanlimab, INCAGN02385, INCAGN02390 in people with Diffuse Large B Cell Lymphoma and Lymphoma, B-Cell, run by University of Alabama at Birmingham.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 6 May 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Identify the optimal biological dose (OBD) for Retifanlimab in combination with INCAGN02385 and INCAGN02390 in relapsed/refractory DLBCL. (time frame: 12 and 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06290622.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2025.

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