FDA Lifts Partial Clinical Hold on Phase 3 Trial Evaluating IFx-2.0 in Advanced Merkel Cell Carcinoma

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The FDA has lifted the partial clinical hold previously placed on a phase 3 trial investigating IFx-2.0 for the treatment of patients with advanced or metastatic Merkel cell carcinoma (MCC), which enables the trial to proceed under the special protocol assessment agreement with the FDA.¹

The study is specifically evaluating the innate immune agonist IFx-2.0 as an adjunctive therapy administered for 3 weeks with concurrent pembrolizumab (Keytruda) at an approved dose compared with pembrolizumab plus placebo for the first-line treatment of patients with advanced or metastatic MCC.

“We are grateful for the collaborative interaction with the reviewers at the Office of Therapeutic Products and the Oncology Center of Excellence, including their quick response time and, importantly, their helpful recommendations going forward,” James Bianco, MD, president and chief executive officer of TuHURA Biosciences, the developer of IFx-2.0, stated in a press release.

In December 2018, the FDA approved pembrolizumab for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic MCC.² The approval was supported by data from the multicenter, nonrandomized, open-label, phase 2 KEYNOTE-017 trial (NCT02267603), which included 50 patients with recurrent locally advanced or metastatic MCC who did not previously receive systemic therapy for advanced disease. Notably, patients were treated with pembrolizumab at 2 mg/kg every 3 weeks.

The phase 3 study is expected to enroll 118 patients with MCC in approximately 20 to 25 sites across the United States.¹ Those enrolled on the study are expected to be randomly assigned 1:1 to receive IFx-2.0 plus pembrolizumab vs pembrolizumab plus placebo for up to 2 years or until disease progression or toxicities related to pembrolizumab.

The primary end point of the study is objective response rate (ORR), and the key secondary end point is progression-free survival (PFS). Other secondary end points include safety, duration of response, and overall survival (OS). Of note, if PFS is achieved without detrimentally affecting OS, the combination of IFx-2.0 and pembrolizumab could be eligible for regular FDA approval without the requirement for a post approval confirmatory trial, which is often typical for most accelerated approval trials.

“The removal of the partial clinical hold allows TuHURA to begin the trial’s initiation and activation of clinical sites for the phase accelerated approval trial of IFx-2.0,” Bianco said in the press release.

Furthermore, in June 2024, a phase 1b trial evaluated IFx-2.0 in patients with advanced or metastatic MCC or cutaneous squamous cell carcinoma (cSCC) who experienced primary resistance to immune checkpoint inhibitors.³ Among patients with advanced MCC who had not previously received ICIs (n = 7), 5 experienced disease progression within 3.8 months following treatment with the single agent anti–PD-1 or anti–PD-L1 therapy.

Notably, patients were rechallenged with an anti–PD-1/anti–PD-L1 therapyafter they were treated with IFx-2.0. Four patients among the 5 who experienced disease progression achieved a durable objective response, which included complete response, partial response (PR), and pathological complete response. Specifically, the durable objective response lasted approximately 25 months, with 2 ongoing responses at 19 and 23 months.

Additionally, after disease progression on the anti–PD-1 therapy, the remaining 2 patients from the patient population were treated with and had disease progression on a combination of anti–PD-1 and anti-CTLA4 treatment before receiving IFx-2.0. Of note, 1 patient achieved a PR after receiving IFx-2.0, which was ongoing at 6 months after rechallenge with single agent anti–PD-1. Data from the phase 1b study served as the rationale for the phase 3 study.

References

1. FDA removes partial clinical hold on TuHURA Biosciences’ phase 3 accelerated approval trial for IFx-2.0 in advanced or metastatic Merkel cell carcinoma. News release. TuHURA Biosciences. June 9, 2025. Accessed June 9, 2025. https://tuhurabio.com/fda-removes-partial-clinical-hold-on-tuhura-biosciences-phase-3-accelerated-approval-trial-for-ifx-2-0-in-advanced-or-metastatic-merkel-cell-carcinoma/
2. FDA approves pembrolizumab for Merkel cell carcinoma. FDA. December 19, 2018. Accessed June 9, 2025. https://www.fda.gov/drugs/fda-approves-pembrolizumab-merkel-cell-carcinoma
3. TuHURA Biosciences and Kintara Therapeutics announce positive results from phase 1b trial of IFx-2.0, a novel personalized cancer vaccine, in checkpoint inhibitor resistant advanced Merkel cell carcinoma (mcc) and cutaneous squamous cell carcinoma (cSCC). News release. TuHURA Biosciences. June 3, 2024. Accessed June 9, 2025. https://tuhurabio.com/tuhura-biosciences-and-kintara-therapeutics-announce-positive-results-from-phase-1b-trial-of-ifx-2-0-a-novel-personalized-cancer-vaccine-in-checkpoint-inhibitor-resistant-advanced-merkel-cell-carcin/