On June 1, 2026 Citius Oncology, Inc. ("Citius Oncology") (Nasdaq: CTOR), an oncology‑focused biopharmaceutical company and majority‑owned subsidiary of Citius Pharmaceuticals, Inc. ("Citius Pharma") (Nasdaq: CTXR), reported Phase 1 clinical data presented May 30, 2026, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting evaluating LYMPHIR (denileukin diftitox-cxdl) in combination with pembrolizumab in patients with recurrent or refractory gynecologic malignancies. The poster presentation (Abstract #2564) was presented by investigators from the University of Pittsburgh Medical Center (UPMC) Magee-Womens Hospital.
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"LYMPHIR’s ability to transiently deplete immunosuppressive regulatory T-cells may help address immune resistance in the tumor microenvironment and enhance the effect of checkpoint inhibitors. The encouraging clinical signals and tolerability profile observed in this study support continued clinical evaluation of this "chemo-free" immunomodulatory approach, especially in tumors where resistance to checkpoint inhibitors remains a significant challenge," said Dr. Myron S. Czuczman, Chief Medical Officer of Citius Oncology.
The open-label Phase 1 study evaluated LYMPHIR in combination with pembrolizumab in 25 heavily pre-treated patients (21 evaluable for efficacy) with recurrent or metastatic solid tumors, primarily gynecologic malignancies. Enrolled patients had received a median of five prior therapies, and more than half had previously received anti-PD-1 or PD-L1 therapy.
Key Efficacy and Safety findings presented at ASCO (Free ASCO Whitepaper) included:
24% Overall Response Rate (ORR) among the 21 efficacy-evaluable patients (5 partial responses).
Median duration of response (mDOR) had not yet been reached because only 1 of the 5 partial responders had progressed at the time of analysis (80% of PRs were continuing to experience clinical benefit). The current duration of response times (time since PR was achieved) were 4.2-35 months with a median of 21.1 months.
33% ORR in endometrial cancer patients previously treated with checkpoint inhibitors, including one patient with an ongoing response greater than three years.
48% of efficacy-evaluable patients (10 of 21) achieved clinical benefit, defined as complete response (CR), partial response (PR), or durable stable disease lasting at least six months:
Median progression-free survival (mPFS) of 20.5 months (95% CI: 6.5 – NA) among the 10 patients who achieved clinical benefit; overall mPFS across all 21 efficacy-evaluable patients was 5.8 months (95% CI: 2.2 – NA);
5 patients had a PFS of > 20 months including 1 patient with > 30 months PFS;
Of the 24/25 pts evaluable for dose limiting toxicities (DLTs), only 1 case of reversible Gr 3 capillary leak syndrome (CLS) was observed at the highest dose level. A maximum tolerated dose was not achieved.
16 serious adverse events were observed in seven patients treated at the highest dose level. No new safety signals or grade 3 or greater immune-related adverse events were observed.
Dr. Alexander Olawaiye, a professor and one of the gynecologic cancer researchers at UPMC Magee-Womens Hospital and lead investigator of the study, added, "Patients with recurrent gynecologic malignancies who progress following immunotherapy often have limited treatment options. The clinical activity observed with denileukin diftitox-cxdl plus pembrolizumab, including durable responses and prolonged disease control in heavily pre-treated patients, is notable. Given the lack of effective salvage treatments for these patients, especially those that have failed prior immune-checkpoint inhibition, the novel combination of LYMPHIR plus pembrolizumab provides a potential viable therapeutic option. Importantly, the safety profile observed was manageable in this heavily pre-treated population, supporting continued evaluation in larger studies."
Ongoing translational studies are evaluating the impact of the combination on regulatory T-cells, immune effector cells, and the tumor microenvironment to help identify potential biomarkers in order to optimize future development strategies. A Phase 2 expansion study is being planned to further evaluate the combination in gynecologic cancers, including less heavily pre-treated and prior immunotherapy-exposed patient populations.
About the Study
This open‑label, dose‑escalation, investigator‑initiated Phase 1 study (NCT05200559), led by Dr. Alexander B Olawaiye at UPMC Magee‑Womens Hospital, enrolled 25 patients with recurrent or metastatic solid tumors who had received at least one prior line of therapy. LYMPHIR was administered intravenously on Days 1–3 of each 21‑day cycle at escalating doses (3, 6, 9, and 12 mcg/kg), along with pembrolizumab (200 mg IV) on Day 1. Patients who completed eight cycles of combination therapy were continued on pembrolizumab monotherapy until disease progression. Citius Oncology provided study drug and financial support to the investigator-initiated study; the study was designed, conducted, and analyzed by the UPMC investigators.
Important note on investigational use: The use of LYMPHIR in this study was investigational and outside of its FDA-approved indication of relapsed or refractory Stage I–III cutaneous T-cell lymphoma. LYMPHIR is not approved by the FDA for the treatment of gynecologic malignancies or any solid tumor, and the safety and efficacy of LYMPHIR in this setting have not been established. This Phase 1 study was not designed or powered to evaluate clinical efficacy, and no conclusions can be drawn regarding comparative effectiveness or long-term outcomes. Early-stage clinical data may not be predictive of results from larger or later-stage studies.
About Gynecologic Cancers
Recurrent or metastatic ovarian and endometrial cancers are two of the most common gynecologic malignancies in the United States. Endometrial cancer is the most frequently diagnosed gynecologic cancer, with an estimated 70,000 new endometrial cancer cases expected in the United States in 20261, while ovarian cancer remains the deadliest with approximately 12,700 deaths per year (51.6%) and approximately 20,000 new diagnoses each year in the United States2. These cancers are often detected at advanced stages, and although many patients initially respond to platinum‑based chemotherapy, most experience relapse and develop resistance. Survival rates in the recurrent setting remain poor, and responses to current immunotherapies such as PD‑1 inhibitors are limited, highlighting a significant unmet need for novel treatment approaches. LYMPHIR’s transient depletion of regulatory T‑cells in combination with anti-PD-1 checkpoint inhibition may potentially enhance host anti‑tumor immune responses and help overcome immunotherapy resistance in these difficult‑to‑treat tumors.
About LYMPHIR (denileukin diftitox‑cxdl)
LYMPHIR is a targeted immune therapy for relapsed or refractory cutaneous T-cell lymphoma (CTCL) indicated for use in Stage I-III disease after at least one prior systemic therapy. It is a recombinant fusion protein that combines the IL-2 receptor binding domain with diphtheria toxin (DT) fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Denileukin diftitox-cxdl-associated anti-tumor activity is achieved via a direct cytocidal action on IL-2R-expressing tumors and depletion of host immunosuppressive regulatory T lymphocytes (Tregs).
In 2021, reformulated denileukin diftitox received regulatory approval in Japan for the treatment of relapsed or refractory CTCL and peripheral T-cell lymphoma (PTCL). Subsequently, in 2021, Citius acquired an exclusive license with rights to develop and commercialize reformulated denileukin diftitox in all markets except for India, Japan and certain parts of Asia. LYMPHIR (denileukin diftitox-cxdl) was approved by the FDA and subsequently launched in the U.S. in December 2025.
(Press release, Citius Oncology, JUN 1, 2026, View Source [SID1234666334])