A combination of two immune-modulating treatments, Lymphir (denileukin diftitox) and Keytruda (pembrolizumab), was well tolerated in an exploratory clinical trial of people with hard-to-treat gynecological cancers.
The Phase 1/2 study (NCT05200559) is sponsored by Alexander Olawaiye, MD, a professor at the University of Pittsburgh. The trial aims to enroll approximately 70 women with various types of solid tumors that have progressed or failed to respond following standard treatments. Recruitment is ongoing at UPMC Hillman Cancer Center in Pittsburgh.
In the Phase 1 portion of the study, 25 women with various types of gynecological cancers were given various doses of Lymphir along with Keytruda at standard doses used for gynecological cancers. The main goal was to evaluate the combination treatment’s safety and identify the optimal dose of denileukin diftitox for further Phase 2 testing.
Keytruda is approved in the U.S. for a wide range of cancer indications, including for uses in several types of gynecological cancer. Lymphir was recently approved in the U.S. for certain patients with cutaneous T-cell lymphoma, a rare cancer caused by the abnormal growth of immune cells in the skin.
Citius Oncology, the company developing Lymphir, said results showed a favorable safety profile. “No unexpected safety signals or serious immune-related adverse events were observed at any dose level,” Citius said in a company press release.
‘We may have a transformational therapy on our hands’
In addition to safety testing, the study also included preliminary efficacy assessments. Of 21 evaluable patients, 24 % had an objective response, meaning their tumors shrank following treatment. Nearly half (48%) of the patients met criteria for clinical benefit, meaning their cancer either shrank or didn’t grow over six months of follow-up.
“The efficacy signal shown by this combination is incredibly exciting considering the minimal impact immuno-oncology has made in ovarian cancer thus far,” Olawaiye said. “If these findings are confirmed in subsequent studies, we may have a transformational therapy on our hands.”
Myron Czuczman, MD, executive vice president and chief medical officer at Citius, said the company is “encouraged by the favorable safety profile and sustained disease control observed in this heavily pretreated patient population.”
Immune cells can kill cancer cells, but tumors often evolve to evade immune destruction. One such mechanism is to express PD-1, a protein that signals killer immune cells not to attack. Another is to increase levels of regulatory T cells (Tregs), which are anti-inflammatory cells that normally help prevent the immune system from accidentally attacking the body’s own tissue, but can be commandeered to defend the tumor (since the tumor is made of the body’s own tissue, just growing abnormally).
Keytruda, sold by Merck, is designed to block PD-1 signaling, thereby disinhibiting killer immune cells to go after the cancer. Lymphir aims to deplete Treg cells, thus leaving tumors more vulnerable to immune attack.
“Evidence from the [Phase 1 clinical trial] suggests augmented anti-tumor activity when [Lymphir] is combined with Keytruda and warrants further exploration in Phase 2 settings,” Czuczman said.
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