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

NCT06290622 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: IRB300012414 (UAB23136)
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Diffuse Large B Cell Lymphoma; Lymphoma, B-Cell; Lymphoma, Follicular

Outcome Measures

Primary Outcomes (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.

  12 and 24 months

Study Arms (1)

Dose Level Assignments

EXPERIMENTAL

Dose 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

Drug: Retifanlimab, INCAGN02385, INCAGN02390

Interventions

Retifanlimab, INCAGN02385, INCAGN02390 DRUG

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.

Dose Level Assignments

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Mayur Narkhede

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 4, 2024
• Study Start: August 30, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): January 31, 2028
• Last Updated: May 6, 2025

Record last verified: 2025-05