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Citius Oncology, Inc., a key player in oncology biopharmaceuticals and a subsidiary of Citius Pharmaceuticals, Inc., recently shared encouraging topline safety and efficacy results from an investigator-initiated Phase 1 trial. This study explored the utility of LYMPHIR™ (E7777, denileukin diftitox?cxdl) when administered as a preparatory treatment before commercial CD19-directed CAR-T cell therapy for patients battling high-risk relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Conducted by leading researchers Dr. Veronika Bachanova at the University of Minnesota and City of Hope, the trial aimed to test a novel immunomodulatory strategy: augmenting the standard lymphodepletion regimen preceding CAR-T infusion. The objective was to potentially boost the anti-tumor effectiveness of the subsequent CAR-T treatment. The full findings were recently presented at the 2026 ASTCT® & CIBMTR® Tandem Meetings.
The Rationale Behind LYMPHIR Pre-treatment
LYMPHIR is an engineered fusion toxin with a known mechanism: it selectively targets and binds to the Interleukin-2 (IL-2) receptor, which is highly expressed on immunosuppressive regulatory T-cells (Tregs). LYMPHIR is already FDA-approved and commercially available for treating relapsed or refractory cutaneous T-cell lymphoma (CTCL) following prior systemic treatment. By transiently depleting these Tregs before CAR-T therapy, researchers hypothesize that the immune system’s ability to recognize and attack cancer cells is significantly improved.
Dr. Myron Czuczman, Executive Vice President and Chief Medical Officer of Citius Oncology and Citius Pharma, highlighted the significance: “Enhancing Treg depletion prior to CAR-T infusion with LYMPHIR represents a promising immunomodulatory strategy in patients with high-risk DLBCL, and these Phase 1 data provide an encouraging signal of the potential to enhance current CAR-T regimens.” He added that these data strongly support the company’s broader focus on exploring LYMPHIR’s modulatory effects in combination with existing treatments to bolster the body’s natural defense against tumors.
Key Phase 1 Results: Safety and Efficacy Signals
The Phase 1, open-label, dose-escalation study (NCT04855253) involved 14 patients who had challenging forms of relapsed or refractory DLBCL, including those with poor prognostic indicators such as double/triple hit genetics, primary refractory disease, or extranodal involvement. Participants received a single dose of LYMPHIR (at 5, 7, or 9 µg/kg) followed by low-dose chemotherapy, leading into their standard commercial CD19-directed CAR-T cell therapy. Patients received one of three established CAR-T products: axicabtagene ciloleucel (Yescarta®), lisocabtagene maraleucel (Breyanzi®), or tisagenlecleucel (Kymriah®).
Crucially, all 14 patients successfully completed the LYMPHIR treatment phase and proceeded to CAR-T infusion.
- Tolerability and Safety: LYMPHIR was reported as well-tolerated across the dose range tested, with no dose-limiting toxicities (DLTs) observed up to 9 µg/kg. No Grade $ge$3 LYMPHIR-related immune adverse events or infusion reactions were noted. Reported side effects were manageable, consisting of Grade 1–2 capillary leak syndrome, fever, and transient liver enzyme elevations. Grade 3 cytopenias observed were consistent with the expected effects of lymphodepletion.
- Pharmacodynamic Effect: Data confirmed effective Treg depletion. A single LYMPHIR dose depleted circulating Tregs in 13 of the 14 patients, with a median reduction of 24 Tregs/µL, peaking at 24 hours post-administration.
- Efficacy Signals (Preliminary): Though the Phase 1 study was not powered for definitive efficacy assessment, encouraging signals were observed at one month: an Overall Response Rate (ORR) of 86%, which comprised a 57% complete response (CR) rate and a 29% partial response (PR) rate. Furthermore, preliminary one-year survival estimates were notably positive: one-year Progression-Free Survival (PFS) reached 77% and one-year Overall Survival (OS) was 84%.
Regarding CAR-T related toxicities, Cytokine Release Syndrome (CRS) occurred in 43% of patients (all Grade 1/2), and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 21% (primarily low grade).
Dr. Veronika Bachanova commented on the findings, stating, “In this high-risk population, LYMPHIR showed a favorable safety profile and promising pharmacodynamic effects when administered prior to CAR-T therapies. This data sets the stage for a larger study to assess its potential to enhance CAR-T efficacy through longer duration of LYMPHIR use.”
Implications for DLBCL Treatment
Diffuse large B-cell lymphoma (DLBCL) remains an aggressive cancer, and while frontline treatments are effective for many, up to 40% of patients face relapse or refractory disease, often with poor outcomes even after CAR-T therapy. The strategy of transiently depleting Tregs to modulate the hostile tumor microenvironment is a critical area of research aimed at improving long-term remission rates in these difficult-to-treat patients.
The investigational use of LYMPHIR in this setting—outside of its current FDA-approved indication—demonstrates its versatility as an immunomodulatory agent. Citius Oncology anticipates that these early positive indicators will support progression to larger studies examining sustained LYMPHIR use to maximize the benefit of modern cell therapies.