TuHURA Biosciences, Kintara Therapeutics: Positive Phase 1b Results for IFx-2.0 Cancer Vaccine in Resistant Merkel, Squamous Cell Carcinomas

TuHURA Biosciences, Inc. and Kintara Therapeutics, Inc. recently shared promising findings from a Phase 1b clinical trial of TuHURA’s lead candidate, IFx-2.0, aimed at addressing resistance to cancer immunotherapy. This announcement was made during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

The Phase 1b trial investigated IFx-2.0 in patients with advanced or metastatic Merkel Cell Carcinoma (MCC) or Cutaneous Squamous Cell Carcinoma (cSCC) who had shown primary resistance to immune checkpoint inhibitor (ICI) therapy. The primary goal was to determine the safety and feasibility of repeated IFx-2.0 administrations. The study met its primary safety endpoint, as more than 80% of participants completed the planned therapy.

Significantly, IFx-2.0 was found to be both safe and well-tolerated with once-weekly dosing over three weeks. Impressively, 80% of ICI-naïve patients with advanced MCC who had not responded to previous treatments like pembrolizumab or avelumab achieved a durable complete response, pathologic complete response, or partial response after undergoing IFx-2.0 therapy followed by rechallenge with an anti-PD(L)-1 checkpoint inhibitor.

Dr. Andrew Brohl from H. Lee Moffitt Cancer Center and Research Institute presented the data, which demonstrated that IFx-2.0 could overcome resistance to ICIs in 63% of patients with advanced MCC. This was particularly notable among patients who had exhausted multiple treatment options, including chemotherapy and investigational drugs, before turning to IFx-2.0.

Of particular interest were seven ICI-naïve advanced MCC patients who had not undergone subsequent systemic or investigational therapies before receiving IFx-2.0. Five of these patients had progressed within 3.8 months on anti-PD(L)-1 therapy. After the IFx-2.0 treatment and rechallenge with an anti-PD(L)-1 agent, four out of five patients achieved a durable objective response lasting an average of 25 months, with two responses ongoing at 19 and 23 months, respectively.

The remaining two patients progressed on both anti-PD-1 therapy and combination anti-PD1/anti-CTLA4 therapy before receiving IFx-2.0. Following the IFx-2.0 treatment, one of these patients achieved a partial response, which was ongoing at six months post-rechallenge with an anti-PD-1 agent.

The promising efficacy results form the basis for TuHURA's planned Phase 3 trial, which aims to evaluate IFx-2.0 as an adjunctive therapy with Keytruda® (pembrolizumab) for ICI-naïve patients with advanced or metastatic MCC. This trial is set to begin enrollment in the latter half of 2024 under the FDA's Accelerated Approval Pathway.

TuHURA's IFx-2.0 is a personalized cancer vaccine that involves injecting a small amount of plasmid DNA (pDNA) into a patient's tumor. This pDNA encodes an immunogenic bacterial protein that is expressed on the tumor surface, making the tumor appear like a bacterium to the immune system. This mechanism is designed to prime the patient’s innate immune response against the tumor, even if the tumor had previously evaded immune detection.

The Phase 1b study's exploratory analysis observed durable disease control in 63% of MCC patients treated with standard ICI agents immediately following IFx-2.0 therapy, suggesting an "immune priming" effect. This promising efficacy supports the planned randomized study of pembrolizumab with or without IFx-2.0 in the first-line treatment of advanced MCC.

TuHURA and Kintara have also entered into a definitive agreement for an all-stock merger, combining their expertise and resources to advance a late-stage oncology pipeline. The merged entity will focus on developing personalized cancer vaccines and first-in-class bi-functional Antibody Drug Conjugates (ADCs). The new company will be named "TuHURA Biosciences, Inc." and will trade on The Nasdaq Capital Market under the ticker "HURA". The merger is expected to conclude in the third quarter of 2024, pending customary closing conditions and stockholder approval.