Clinical Trial Feature: IFx-Hu2.0 Followed By Pembrolizumab In Checkpoint Inhibitor Naïve Participants With Advanced MCC

A new Phase 2/3 clinical trial led by TuHURA Biosciences will evaluate the investigational therapy IFx-Hu2.0 (an innate immune stimulator, related to a streptoccal protein) in combination with pembrolizumab in patients with advanced Merkel cell carcinoma (MCC). While PD-(L)1 inhibitors like pembrolizumab have revolutionized treatment for advanced MCC, over half of patients do not experience long-term disease control. This multicenter, randomized, double-blind, placebo-controlled study aims to improve these outcomes by enhancing antitumor immune activity directly within the tumor microenvironment. 

IFx-Hu2.0 is administered intralesionally into cutaneous, subcutaneous, or nodal MCC lesions, where it stimulates innate immune responses that generate tumor-specific B and T cells. When combined with pembrolizumab, this local immune activation may amplify checkpoint inhibition, promoting more durable systemic antitumor effects. Participants randomized to the experimental arm will receive an IFx-Hu2.0 injection weekly for the first 3 weeks, along with pembrolizumab every three weeks, while the placebo group will receive pembrolizumab and a sodium chloride injection rather than IFx-Hu2.0. The study is being conducted under an FDA Special Protocol Assessment, a designation that supports potential regulatory approval if endpoints are met. The trial plans to enroll 118 participants across 25 U.S. sites and will remain open for enrollment until March 2027.

Eligibility Criteria  
Key inclusion criteria include:  

• Adults ≥18 years with advanced or metastatic MCC  

• Histologically confirmed MCC with unresectable Stage III or IV disease  

•  Participants must not have received a checkpoint inhibitor treatment   

• ECOG Performance Status <2  

• At least one injectable MCC lesion ≥3 mm (cutaneous, subcutaneous, or nodal)  

• Must have measurable disease according to RECIST v1.1.  

• Life expectancy ≥6 months  

• Adequate organ function  

• Willingness to provide tumor tissue for biomarker analyses  

Key exclusion criteria include:  

• Active brain metastases (with some treated/stable exceptions)  

• Prior systemic anticancer treatment for advanced or metastatic MCC  

• Active autoimmune disease requiring systemic treatment  

• Uncontrolled illness (e.g., infections, cardiac conditions)  

   

Learn more about the trial here: Study Details | NCT06947928 | Placebo-Controlled Trial of IFx-Hu2.0 Followed By Pembrolizumab In Checkpoint Inhibitor Naïve Participants With Advanced Or Metastatic Merkel Cell Carcinoma | ClinicalTrials.gov