FDA Lifts Hold on IFx-2.0 in Advanced/Metastatic Merkel Cell Carcinoma

Pembrolizumab was previously granted FDA accelerated approval as a monotherapy for adult and pediatric patients with recurrent locally advanced or metastatic MCC in December 2018.

The FDA has lifted a manufacturing-related partial clinical hold on a phase 3 accelerated approval trial for the immune agonist IFx-2.0 for the treatment of patients with advanced or metastatic Merkel cell carcinoma (MCC), according to a news release from the drug’s developer, TuHURA Biosciences, Inc.1

The phase 3 trial will evaluate IFx-2.0 as an adjunctive therapy vs placebo, with pembrolizumab (Keytruda) in the frontline setting for this patient group conducted under Special Protocol Agreement with the FDA and is planned for later in June 2025.

“We are grateful for the collaborative interaction with the reviewers at the Office of Therapeutic Products (OTP) and the Oncology Center of Excellence (OCE), including their quick response time and, importantly, their helpful recommendations going forward,” James Bianco, MD, president and chief executive officer of TuHURA Biosciences, said in the news release.1 “The removal of the partial clinical hold allows [the developers] to begin the trial’s initiation and activation of clinical sites for the phase 3 accelerated approval trial of IFx-2.0.”

Patients in the phase 3 study will be randomly assigned 1:1 to receive pembrolizumab and either IFx-2.0 or placebo. The trial is expected to enroll approximately 118 patients across 22 to 25 US sites. IFx-2.0 will be administered via intralesional injection weekly for 3 weeks concurrent with 200 mg of pembrolizumab given intravenously every 3 weeks vs matching placebo-pembrolizumab.2 Treatment will be administered for a maximum of 2 years, or until disease progression or unacceptable pembrolizumab-related toxicities.

The primary end point of the trial is objective response rate (ORR). A key secondary end point is progression-free survival (PFS). Other secondary end points include safety, duration of response, and overall survival (OS). Accelerated approval is based on the successful attainment of the ORR primary end point, and a regular approval could be satisfied if the PFS key secondary end point is met, provided no detrimental effects are observed for OS.

Pembrolizumab was previously granted FDA accelerated approval as a monotherapy for adult and pediatric patients with recurrent locally advanced or metastatic MCC in December 2018.3 The approval was based on results from the phase 2 KEYNOTE-017 trial (NCT022676603).

Efficacy data from the trial revealed that, of 50 patients who were treatment-naïve for advanced disease who received 2 mg/kg of pembrolizumab every 3 weeks, the ORR per blinded independent central review was 56% (95% CI, 41%-70%), with a complete response rate of 24%. Additionally, among responders (n = 28), 96% had a response duration greater than 6 months and 54% had responses greater than 12 months.

According to extended follow-up data from the phase 2 trial published in the Journal for ImmunoTherapy of Cancer, treatment-related adverse effects (TRAEs) occurred in 98% of patients treated with single-agent pembrolizumab, 30% of whom experienced grade 3 or higher TRAEs.4 A total of 16% of patients discontinued treatment due to TRAEs, and a single treatment-related death occurred. Additionally, immune-mediated TRAEs and infusion-site reactions occurred in 32% of patients.

Patients 18 years and older in the phase 2/3 trial evaluating IFx-2.0 were eligible for enrollment if they had: a life expectancy of at least 6 months; an ECOG performance score of 0 to 2; recurrent and/or resectable stage III or IV disease based on American Joint Committee on Cancer criteria and histologically confirmed MCC; and not received previous checkpoint inhibition. Those eligible for enrollment must also be willing to provide tumor tissue from an archival core biopsy or resected site of disease for biomarker analyses, as well as adequate hematologic, hepatic, and renal function.

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, Inc. June 9, 2025. Accessed June 9, 2025. https://tinyurl.com/5hbxdd99
2. Placebo-controlled trial of IFx-Hu2.0 followed by pembrolizumab in checkpoint inhibitor naïve patients with advanced or metastatic Merkel cell carcinoma. ClinicalTrials.gov. Updated April 27, 2025. Accessed June 9, 2025. https://tinyurl.com/3yhkzsxw
3. FDA approves pembrolizumab for Merkel cell carcinoma. News release. FDA. December 19, 2018. Accessed June 9, 2025. https://tinyurl.com/57pvtd7z
4. Nghiem P, Bhatia S, Lipson EJ, et al. Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. J Immunother Cancer. 2021;9:e002478. doi:10.1136/jitc-2021-002478