IFx-Hu2.0 Enters Clinical Trials for Merkel Cell Carcinoma
Trials of IFx-Hu2.0 are initiating, looking to overcome checkpoint inhibitor resistance in Merkel cell carcinoma.
Concept illustration of skin cancer
A phase 1b/2a clinical trial (NCT06940440) evaluating the innate immune agonist IFx-Hu2.0 in patients with noncutaneous Merkel cell carcinoma (MCC) of unknown primary has begun.1
This patient cohort is distinct from those eligible for TuHURA Biosciences, Inc’s upcoming phase 3 registrational trial (NCT06947928), which is expected to begin enrollment later in the second quarter of 2025.
IFx-Hu2.0 is designed to address primary resistance to checkpoint inhibitors (CPIs) like pembrolizumab (Keytruda). In previous phase 1 and 1b studies involving melanoma and metastatic MCC, IFx-Hu2.0 demonstrated a systemic antitumor immune response when administered intratumorally into cutaneous, subcutaneous, or nodal lesions.
"Like our planned phase 3 accelerated approval trial, this phase 1b/2a trial will also investigate the ability of IFx-Hu2.0 to increase the antitumor response rate when used alongside [pembrolizumab] in first line treatment of CPI-naive, metastatic MCC. However, unlike the planned phase 3 study, these are patients without skin lesions who present with metastatic deep-seated tumors in the liver, lungs or retroperitoneum (abdomen),” said James Bianco, MD, president and chief executive officer of TuHURA Biosciences, in a press release.
“Up to 30% of patients with MCC present without primary lesions in the skin, so this trial will not only provide safety, feasibility, and efficacy data, but may also expand the potential number of addressable patients who may benefit from IFx-Hu2.0,” he continued.
Phase 1b/2a Trial Overview
This newly initiated multicenter, open-label study plans to evaluate the safety and feasibility of IFx-Hu2.0 as an adjunct to pembrolizumab for the treatment of adult patients with visceral MCC lesions. The trial will enroll 9 patients across 3 visceral lesion sites, including hepatic, pulmonary, and retroperitoneal, with 3 patients per cohort.2
Patients will receive a weekly intratumoral injection of IFx-Hu2.0 (0.1 mg) for 3 weeks. Pembrolizumab will be given to patients within 48 hours of the first IFx-Hu2.0 dose and continued every 3 weeks for 6 months.
The primary end points of the trial are safety and feasibility at day 49 (28 days post final IFx-Hu2.0 dose), and the secondary end points are efficacy based on RECIST 1.1 at 3 and 6 months.
Initial data are expected in late 2025 or early 2026.
"If feasibility and safety is demonstrated for IFx-Hu2.0 and [pembrolizumab] when radiologically administered to deep-seated tumors, we plan to extend enrollment to a variety of non-MCC cancers that are known not to respond or respond poorly to CPIs. Since the underlying biology of why tumors don't respond to CPIs is for the most part the same, then the mechanism of how IFx-Hu2.0 overcomes that resistance to CPIs should be independent of the type of cancer treated. We have previously demonstrated that IFx-Hu2.0 can overcome CPI resistance in melanoma, squamous cell, and Merkel cell carcinoma, 3 unrelated types of skin cancers. If successful, this trial could expand the potential benefit of IFx-Hu2.0 to a wide variety of cancers," added Bianco in the press release.
Preparations for Phase 3 Accelerated Approval Trial
In addition to this study, the company is preparing to initiate a randomized, placebo-controlled, phase 3 trial of IFx-Hu2.0 combined with pembrolizumab vs pembrolizumab plus placebo in checkpoint inhibitor-naive patients with advanced or metastatic MCC.3
In the experimental arm of the study, patients will receive IFx-Hu2.0 at a dose of 0.1 mg via intralesional injection in a single lesion once per week for 3 consecutive weeks. Pembrolizumab at a dose of 200 mg will also be administered intravenously (IV) on visit 1, then every 3 weeks until disease progression, unacceptable immune-related toxicities, or 2 years.
In the control arm, patients will receive a placebo intralesional injection in a single lesion once per week for 3 consecutive weeks. Pembrolizumab at the same dose used in the experimental arm will be given to patients via IV infusion on visit 1, then every 3 weeks until disease progression, unacceptable immune-related toxicities, or 2 years.
Enrollment is open to patients aged 18 years or older with an ECOG performance status of ≤ 2; a life expectancy of at least 6 months; adequate hematologic, hepatic, and renal organ function; and recurrent and/or unresectable stage III or stage IV MCC per the American Joint Committee on Cancer (8th edition). Patients must also have at least 1 injectable lesion equal to or greater than 3 mm, measurable disease as defined by RECIST 1.1, and should be CPI naive.
The primary end point of the study is objective response rate at 24 weeks. The study’s secondary end point is progression-free survival per RECIST 1.1.
Further, the FDA has agreed to lift a partial clinical hold previously placed on the trial, contingent on TuHURA fulfilling certain criteria in the second quarter of 2025.1
