TuHURA Biosciences, Inc. and Kintara Therapeutics, Inc. announced positive results from the primary analysis of TuHURA's completed Phase 1b trial evaluating IFx-2.0 among patients with advanced or metastatic MCC or cSCC who exhibited primary resistance to immune checkpoint inhibitor (ICIs) therapy. The group that was of most interest were the seven (7) patients with ICI naïve, advanced MCC, who, prior to IFx-2.0 treatment, received no subsequent systemic or investigational therapies that may confound the ability to determine IFx-2.0's contribution to overcoming primary resistance to ICI therapy. Five (5) of these 7 patients progressed within 3.8 months while receiving single agent anti-PD(L)-1 therapy.

IFx-2.0 was administered as the immediate post ICI therapy. Following IFx-2.0 treatment, patients were rechallenged with an anti-PD(L)-1 agent. Four (4) of the 5 patients (80%) achieved a durable objective response (CR, pCR, 2 PRs) lasting, on average, 25 months, with 2 responses ongoing at 19 and 23 months.

The remaining 2 of 7 patients, after progressing on anti-PD-1 therapy, also received and progressed on combination anti-PD1/anti-CTLA4 therapy prior to IFx-2.0 treatment. Following IFx-2.0, 1 patient (50%) achieved a PR, ongoing at 6 months following rechallenge with single agent anti-PD-1 rechallenge. The promising efficacy signal demonstrated in the Phase 1b study showing the potential for IFx-2.0 to overcome primary resistance to anti-PD(L)-1 therapy formed the rationale for TuHURA's planned Phase 3 registration-directed clinical trial.

The Phase 3 trial will examine IFx-2.0 as an adjunctive therapy with Keytruda® (pembrolizumab, an anti-PD-1 agent) to improve tumor overall response rates when compared to Keytruda® plus placebo in first line treatment of ICI naïve patients with advanced or metastatic MCC. This Phase 3 trial is expected to begin enrollment in 2H 2024 under the FDA's Accelerated Approval Pathway. TuHURA's IFx-2.0 personalized cancer vaccine product involves the injection into a patient's tumor of a small amount of pDNA that is designed to encode for an immunogenic bacterial protein that gets expressed on the surface of the patient's tumor so that the surface of the tumor looks like a bacterium.

By making the surface of a tumor look like a bacterium, IFx-2.0 is designed to use each patient's tumor itself as the source of foreign neoantigens to prime and initiate a patient's innate immune response against the tumor irrespective of whether the tumor escaped immune recognition prior to IFx-2.0 administration. In doing so, IFx-2.0 is designed to harness the power of the patient's innate immune response, which has evolved over time to be conserved to detect foreign pathogens like bacterial proteins. The primary objective of the Phase 1b study was to establish safety and feasibility of repeated administrations of IFx-2.0. The study met its primary safety objective: 80% completion of planned study therapy was predefined as a successful feasibility outcome.

Given the proposed potential for immune priming effects of IFx-2.0, researchers performed an unplanned exploratory analysis of post-protocol treatment efficacy to evaluate response to ICI rechallenge. As reported at ASCO, following completion of protocol directed therapy, 11 patients with MCC and 6 patients with cSCC who, prior to study entry, failed anti-PD(L)1 or anti-PD-1/CTLA-4 therapy, were re-treated with anti-PD(L)1 monotherapy or combination therapy as the immediate IFx-2.0 post-protocol therapy: pembrolizumab (7), nivolumab + ipilimumab (2), or avelumab (2) in MCC and cemiplimab (6) in cSCC. The study concluded that IFx-Hu2.0 is safe and well tolerated at weekly dosing repeated up to 3 weeks.

In an exploratory post-hoc analysis, 7 of 11 MCC patients (63%) treated with standard of care ICI agents immediately following protocol therapy experienced durable disease control despite prior failure of this same drug class prior to protocol enrollment, suggesting an "immune priming" effect of study therapy. Based on this promising efficacy signal, a randomized study of pembrolizumab +/- IFx-Hu2.0 is planned in the advanced MCC 1st line setting.