FDA grants fast track designation for new drug IK-175 in combination with nivolumab for advanced uroepithelial carcinoma, with preliminary trial data showing encouraging, durable antitumor activity and a favorable safety profile
The US Food and Drug Administration (FDA) has granted Fast Track designation for the novel aryl hydrocarbon receptor (AHR) antagonist IK-175 in combination with nabumab (Nivolumab) for the treatment of patients with advanced uroepithelial carcinoma whose disease progresses within three months of receiving a dose of the immune checkpoint inhibitor assay.
Fast Track designation: refers to an incentive initiative established to facilitate the treatment of major diseases or diseases where there is an urgent need for more promising drugs to be developed. Drugs in development that are fast-tracked will receive additional opportunities to communicate with the FDA, access to FDA guidance and the right to be included in priority or accelerated approvals, which can be very beneficial for future approval to market.
Patients with urothelial carcinoma generally have a range of standard treatments including surgery, chemotherapy, radiotherapy and immunotherapy (including immune checkpoint inhibitors).
The anti-cancer target of IK-175 is called AHR, a protein that modulates the body's immune system, plays a key role in immunosuppression (making it difficult for immune cells to kill cancer cells) in the tumour microenvironment, and is highly expressed in a variety of cancers including lung, colorectal, head and neck cancers.
A Phase 1 IK-175-001 trial (NCT04200963) is currently evaluating the efficacy of IK-175 as monotherapy and in combination with Nivolumab in the treatment of patients with locally advanced or metastatic solid tumours, including urothelial carcinoma.
Preliminary clinical data from the trial were presented at the Society for Immunotherapy of Cancer (SITC) annual meeting in 2022. The results of the trial showed that IK-175 demonstrated encouraging and durable anti-tumour activity both as a single agent and in combination in patients with uroepithelial carcinoma.
Trial details
In the dose-escalation portion of the trial, 15 patients with advanced solid tumours were recruited to receive IK-175 monotherapy and 5 patients received IK-175 in combination with Nivolumab.
The trial results showed that three patients in the monotherapy arm maintained stable disease for 16 weeks and two patients in the combination arm maintained stable disease for 74 weeks.
During the dose expansion phase of the trial, 10 patients with uroepithelial carcinoma were recruited to receive IK-175 monotherapy and 10 patients received the combination of IK-175 and Nivolumab.
The results of the trial showed that one person in the monotherapy group and two in the combination treatment group had significant tumour shrinkage in the monotherapy group and two in the combination group. In addition, one tumour remained stable in the monotherapy group and two tumours remained stable in the combination group. Overall, the disease control rates were 20% and 40% in the monotherapy and combination groups respectively.
The trial is still recruiting patients. The dose escalation arm of the trial is focused on patients with locally advanced or metastatic tumours. The dose escalation arm of the trial is focused on patients with unresectable locally recurrent or metastatic uroepithelial cancer who have failed all standard treatments and the expansion cohort includes patients with high levels of AHR by immunohistochemistry.
In terms of safety, no dose-limiting toxicity was observed in either arm and the maximum tolerated dose was not reached.
In the combination treatment arm, two serious treatment-related adverse events (AEs) were reported, grade 3 generalised weakness and grade 3 immune-mediated arthritis. Suspected immune-related adverse events included rash, proteinuria, generalised weakness, immune-mediated arthritis, and adrenocortical insufficiency.
"Many patients with uroepithelial carcinoma often have no other treatment options after disease progression on immune checkpoint inhibitors, and there is an urgent need for new treatment options. the fast track designation of IK-175 by the FDA demonstrates the great potential of AHR antagonists to overcome checkpoint inhibitor resistance, and we will continue to expand IK-175 in combination with Nivolumab in combination with locally advanced or metastatic solid tumours, beyond just uroepithelial cancer, so that hopefully more cancer patients will benefit from this therapy." Dr. Sergio Santillana, Chief Medical Officer of Ikena Oncology, the company that manufactures IK-175, said in a press release.
