TuHURA Biosciences Starts Phase 1b/2a Trial of IFx-Hu2.0 with Keytruda for Metastatic MCCUP

TuHURA Biosciences, Inc., a company specializing in immune-oncology, has recently begun a Phase 1b/2a trial for its leading innate immune agonist, IFx-Hu2.0. This trial is focused on treating patients suffering from MCCUP, who are not eligible for the upcoming Phase 3 trial set to start later in 2025. The aim of IFx-Hu2.0 is to address primary resistance to checkpoint inhibitors, such as Keytruda®, and it has shown promising systemic anti-tumor specific immune responses in previous trials with melanoma and advanced or metastatic Merkel cell carcinoma.

Similar to the forthcoming Phase 3 trial, this Phase 1b/2a study will assess IFx-Hu2.0's potential to improve the anti-tumor response when used in conjunction with Keytruda® for first-line treatment of metastatic MCC. Unlike the Phase 3 trial, this study targets patients who do not have cutaneous tumors but instead have metastatic deep-seated tumors located in the liver, lungs, or retroperitoneum. This demographic comprises a significant portion of MCC patients who present without primary skin lesions. Thus, the trial aims not only to gather data on safety, feasibility, and effectiveness, but also to widen the pool of patients that could benefit from IFx-Hu2.0.

Dr. James Bianco, President and CEO of TuHURA Biosciences, conveyed that if the trial demonstrates the safety and feasibility of IFx-Hu2.0 when administered radiologically to deep-seated tumors, the company plans to broaden the study to encompass various non-MCC cancers known for their poor response to CPIs. The rationale is that the biological mechanisms causing CPI resistance are largely consistent, so the method by which IFx-Hu2.0 overcomes this issue should be applicable to other cancer types. IFx-Hu2.0 has already shown success in overcoming CPI resistance in melanoma, squamous cell, and Merkel cell carcinoma.

The Phase 1b/2a trial will be conducted as an open-label, multicenter study assessing the safety and feasibility of using IFx-Hu2.0 alongside pembrolizumab in adults with non-cutaneous MCC. A total of nine patients will be enrolled, each with hepatic, pulmonary, or retroperitoneal lesions. IFx-Hu2.0 will be administered once a week for three weeks, followed by pembrolizumab within 48 hours of the initial IFx-Hu2.0 injection and subsequently every three weeks for six months. The primary endpoint of the study is to evaluate the safety and feasibility of IFx-Hu2.0 as an adjuvant therapy 28 days after the last dose. Secondary endpoints will assess efficacy according to RECIST 1.1 criteria at three and six months, with results expected by the end of 2025 or early 2026.

In parallel, TuHURA is preparing for a Phase 3 trial that will compare the efficacy of IFx-2.0 as an adjunctive therapy to Keytruda® against Keytruda® plus placebo in treating patients with advanced or metastatic MCC who have not previously received checkpoint inhibitors. The trial's primary endpoint is the overall response rate at approximately 24 weeks, with a secondary focus on progression-free survival. The FDA has provided guidance under its accelerated approval pathway, agreeing to the use of Objective Response Rate as the primary endpoint. Additionally, if progression-free survival is achieved favorably, the company may not be required to conduct a post-approval confirmatory trial. TuHURA expects to initiate this Phase 3 trial in the second quarter of 2025.