Citius Oncology, Inc. (Citius Oncology), an oncology-focused biopharmaceutical company and majority-owned subsidiary of Citius Pharmaceuticals, Inc. (Citius Pharma) announced positive topline results from a completed investigator-initiated phase?1 clinical trial conducted by University of Pittsburgh investigators. This study evaluated the direct T-regulatory (Treg) cell depletion activity of Lymphir (denileukin diftitox-cxdl) in combination with the PD-1 immune checkpoint inhibitor pembrolizumab (Keytruda) in patients with recurrent or refractory gynaecologic cancers, including ovarian and endometrial malignancies.
Patients with relapsed or refractory gynecological cancer have poor prognoses and very limited treatment options. This dose-escalation phase 1 non-chemotherapy based clinical study aimed to establish a recommended dose of Lymphir in combination with pembrolizumab for a phase 2 study. In 25 evaluable patients, no unexpected safety signals or serious immune-related adverse events were observed at any dose level.
"We are encouraged by the favourable safety profile and sustained disease control observed in this heavily pretreated patient population. Evidence from the study suggests augmented anti-tumour activity when Lymphir is combined with Keytruda and warrants further exploration in phase?2 settings," stated Dr Myron Czuczman, executive vice president and chief medical officer of Citius Oncology and Citius Pharma.
The trial explored efficacy and demonstrated a 24?% objective response rate (ORR) and a 48?% clinical benefit rate (CBR, defined as complete response, partial response and/or stable disease for six months or greater) among 21 evaluable patients. Full safety and clinical efficacy results are expected to be presented at an international cancer conference later this year.
"The efficacy signal shown by this combination is incredibly exciting considering the minimal impact immuno-oncology has made in ovarian cancer thus far. If these findings are confirmed in subsequent studies, we may have a transformational therapy on our hands," said Dr. Alexander Olawaiye, principal investigator of the study.
This open-label, dose-escalation, investigator-initiated phase?1 study (NCT05200559), led by Dr. Alexander B Olawaiye at UPMC Magee-Women's Hospital, enrolled patients with recurrent or metastatic solid tumours 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.
The use of Lymphir in this study was investigational and outside of its FDA-approved indication. The 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.
Recurrent or metastatic ovarian and endometrial cancers are two of the most common gynaecologic malignancies in the United States. Endometrial cancer is the most frequently diagnosed gynaecologic cancer, with an estimated 70,000 new cases expected in 20261, while ovarian cancer remains the deadliest with approximately 12,700 deaths per year (51.6% 5 year survival) and approximately 20,000 new diagnoses each year2. 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 may enhance anti-tumour immune responses and help overcome immunotherapy resistance in these difficult-to-treat tumours.
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 demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) and antitumor activity through a direct cytocidal action on IL-2R-expressing tumours.
In 2021, 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 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 US in December 2025.
Citius Oncology, Inc. is a platform to develop and commercialize novel targeted oncology therapies. In December 2025, Citius Oncology launched Lymphir, approved by the FDA for the treatment of adults with relapsed or refractory Stage I–III CTCL who had had at least one prior systemic therapy. Management estimates the initial market for Lymphir currently exceeds $400 million, is growing, and is underserved by existing therapies. |