CRANFORD, N.J., June 1, 2026
Citius Oncology has announced encouraging Phase 1 clinical findings evaluating LYMPHIR® (denileukin diftitox-cxdl) in combination with pembrolizumab for the treatment of recurrent or refractory gynecologic malignancies, highlighting the potential of a novel immunomodulatory strategy to address treatment resistance in advanced cancers. The investigator-initiated study, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated durable responses, prolonged disease control, and a manageable safety profile among heavily pre-treated patients who had exhausted multiple prior treatment options. Notably, nearly half of efficacy-evaluable participants achieved meaningful clinical benefit, while patients with relapsed or refractory endometrial cancer experienced particularly encouraging outcomes. The results support continued development of the combination as a potential chemotherapy-free therapeutic approach designed to enhance immune checkpoint inhibitor activity and improve outcomes in difficult-to-treat gynecologic cancers.
LYMPHIR and Pembrolizumab Deliver Durable Clinical Responses
The open-label Phase 1 trial enrolled 25 patients with recurrent or metastatic solid tumors, primarily gynecologic malignancies, including individuals who had received a median of five prior treatment regimens. More than half of participants had previously been treated with anti-PD-1 or PD-L1 immunotherapies, reflecting a particularly challenging patient population. Among the 21 efficacy-evaluable patients, investigators reported an overall response rate (ORR) of 24%, with five patients achieving partial responses.
Importantly, responses appeared highly durable, with 80% of responding patients continuing to experience clinical benefit at the time of analysis. Duration of response ranged from 4.2 months to 35 months, with a median duration of response of 21.1 months. These findings suggest that the combination therapy may help overcome immune resistance mechanisms that often limit the effectiveness of existing checkpoint inhibitor treatments. The study also reported a 33% objective response rate in endometrial cancer patients previously treated with checkpoint inhibitors, including one patient who maintained an ongoing response for more than three years.
Significant Disease Control Observed in Heavily Pretreated Patients
Advertisement
One of the most notable findings from the study was the high level of disease control achieved despite the advanced disease status of enrolled participants. Approximately 48% of efficacy-evaluable patients achieved clinical benefit, defined as complete response, partial response, or durable stable disease lasting at least six months. Among these patients, the median progression-free survival (PFS) reached 20.5 months, substantially exceeding expectations for heavily pretreated recurrent gynecologic malignancies.
Across the entire efficacy-evaluable population, median progression-free survival was 5.8 months, while five patients remained progression-free for more than 20 months, including one patient exceeding 30 months of disease control. Investigators emphasized that recurrent ovarian and endometrial cancers remain among the most difficult gynecologic cancers to manage, particularly after progression following immunotherapy. The encouraging efficacy signals observed with LYMPHIR and pembrolizumab suggest a potential new therapeutic avenue for patients with limited treatment alternatives and poor prognoses.
Novel Immunomodulatory Approach Shows Manageable Safety Profile
LYMPHIR is designed to transiently deplete regulatory T cells (Tregs), which are known to suppress anti-tumor immune responses and contribute to resistance against checkpoint inhibitors. By reducing immunosuppressive activity within the tumor microenvironment, the therapy may enhance the effectiveness of pembrolizumab and improve immune-mediated cancer cell destruction. The safety findings reported at ASCO were generally favorable, with only one reversible Grade 3 case of capillary leak syndrome observed at the highest dose level and no maximum tolerated dose reached during dose escalation.
Although serious adverse events were reported among patients treated at higher doses, investigators noted that no new safety signals emerged and no Grade 3 or higher immune-related adverse events were observed. Based on these encouraging results, ongoing translational research is evaluating biomarkers associated with treatment response, while a planned Phase 2 expansion study will further assess the combination in gynecologic cancer patients, including those previously exposed to immunotherapy. If future studies confirm these findings, LYMPHIR combined with pembrolizumab could emerge as a promising new immunotherapy strategy capable of addressing one of the most pressing unmet needs in gynecologic oncology.
Source: Citius Oncology press release
