On June 3, 2024 TuHURA Biosciences, Inc. ("TuHURA"), a Phase 3 registration-stage immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy and Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported 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 (Press release, Kintara Therapeutics, JUN 3, 2024, View Source [SID1234644016]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The abstract titled, "Phase 1b trial of IFx-Hu2.0, a novel in situ cancer vaccine, in checkpoint inhibitor-resistant Merkel Cell Carcinoma (MCC) and Cutaneous Squamous Cell Carcinoma (cSCC)," was presented by Andrew Brohl, MD, H. Lee Moffitt Cancer Center and Research Institute, in a poster presentation as part of the Melanoma/Skin Cancers session held at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.
"It is encouraging that IFx-2.0 demonstrated the ability to overcome resistance to ICI in 63% of patients with advanced MCC, even in patients who progressed on both anti-PD1 therapy followed by anti-PD1/CTLA-4 combination therapy, many of whom also received chemotherapy and several investigational agents post ICI failure and prior to IFx-2.0 treatment," commented Dr. James Bianco, Chief Executive Officer of TuHURA.
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 (Free ASCO Whitepaper), 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.
For more information about TuHURA’s Phase 1b IFx-2.0 study, visit clinicaltrials.gov and reference identifier: NCT04160065.
As previously announced, TuHURA entered into a definitive agreement for an all-stock transaction with Kintara to form a company combining expertise and resources to advance a risk diversified late-stage oncology pipeline. In conjunction with the execution of the definitive agreement, TuHURA entered into subscription agreements for a $31 million financing. The combined company will focus on advancing TuHURA’s personalized cancer vaccine(s) and first-in-class bi-functional Antibody Drug Conjugates ("ADCs"), two technologies that seek to overcome the major obstacles that limit the effectiveness of current immunotherapies in treating cancer. The combined company is expected to operate under the name "TuHURA Biosciences, Inc." and to trade on The Nasdaq Capital Market under the ticker "HURA". The transaction is subject to customary closing conditions, including stockholder approval of both companies, and is expected to close in the third quarter of 2024.