06/03/2026  |   Marisa Wexler  |  Rare Cancer News

https://rarecancernews.com/news/immunotherapy-duo-shows-promise-tough-gynecological-cancers/ 

Lymphir-Keytruda combo benefits nearly half of patients in early trial

A combination of the immune-modulating treatments Lymphir (denileukin diftitox) and Keytruda (pembrolizumab) led to clinical benefit in nearly half of evaluable patients in an exploratory clinical trial testing the combo in people with hard-to-treat gynecological cancers, according to new data announced by Lymphir’s developer Citius Oncology.

“Patients with recurrent gynecologic malignancies who progress following immunotherapy often have limited treatment options. The clinical activity observed with [Lymphir] plus [Keytruda], including durable responses and prolonged disease control in heavily pre-treated patients, is notable,” study sponsor and lead investigator Alexander Olawaiye, MD, a professor of gynecologic oncology at the University of Pittsburgh, said in a press release from Citius.

Immunotherapies are a class of cancer drugs that work by helping the immune system attack and eliminate tumor cells. Keytruda is a checkpoint inhibitor, meaning it works by blocking signals that cancer cells exploit to evade immune destruction. It is sold by Merck and is approved in the U.S. for use in many cancer types, including in some patients with gynecological cancer.

Lymphir, meanwhile, works by depleting regulatory T-cells. These cells normally prevent the immune system from attacking the body’s own tissues, but since cancers are, by definition, the body’s own tissues growing abnormally, T-cells often end up inadvertently protecting tumors. Lymphir is approved only for certain people with cutaneous T-cell lymphoma, a rare cancer marked by the abnormal growth of certain immune cells in the skin.

“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,” said Myron Czuczman, MD, Citius’ chief medical officer.

Focus on 25 women
The new data come from an investigator-initiated Phase 1/2 study (NCT05200559) testing the Lymphir-Keytruda combination in various types of solid tumors that have progressed following prior lines of treatment. The data specifically focused on 25 women with heavily pre-treated cancer, most of whom had gynecological malignancies.

Safety data from evaluable patients showed the therapy has been generally well tolerated. A total of 16 serious safety issues have been documented among seven patients given the highest tested dose of Lymphir, including one serious but reversible case of capillary leak syndrome (a condition where fluid leaks out of blood vessels into the surrounding tissue).

Citius’ announcement didn’t provide further detail on the safety findings, but the company said the safety data have been in line with the known profiles of Lymphir and Keytruda.

“Importantly, the safety profile observed was manageable in this heavily pre-treated population, supporting continued evaluation in larger studies,” Olawaiye said.

As of the latest follow-up, 21 patients were eligible for treatment efficacy evaluation. In all these patients, median progression-free survival (that is, the time without disease worsening or death) was just under six months.

Among the 21 evaluable patients, 10 (48%) showed evidence of clinical benefit: Five had a partial response (meaning the tumor got smaller, but didn’t disappear entirely), and the other five had stable disease (meaning the tumor didn’t shrink but also didn’t grow for at least six months). Among these 10 patients, the median progression-free survival was more than 20 months, with at least one patient showing an ongoing response lasting more than three years.

Citius also noted that, in a subset of patients with endometrial cancer who had previously been treated with checkpoint inhibitors, 33% responded to treatment.

“Given the lack of effective salvage treatments for [people with heavily pre-treated gynecological cancers] especially those that have failed prior immune-checkpoint inhibition, the novel combination of Lymphir plus [Keytruda] provides a potential viable therapeutic option,” Olawaiye said.

Citius said plans are underway for a Phase 2 extension study to test the combo of Lymphir and Keytruda in a wider population of gynecological cancer patients.

“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,” Czuczman said.