FDA Lifts Partial Clinical Hold on IFx-2.0 Phase 3 Trial for Merkel Cell Carcinoma
TuHURA Biosciences advances its phase 3 trial of IFx-2.0 for Merkel cell carcinoma, aiming to enhance immune response alongside pembrolizumab.
Histologic image of skin cancer
- The FDA has lifted a partial clinical hold related to manufacturing, allowing TuHURA Biosciences to proceed with site activation and initiation of its phase 3 trial of IFx-2.0 (NCT06947928) in advanced/metastatic Merkel cell carcinoma (MCC).
- IFx-2.0 is an intralesional innate immune agonist that induces expression of a bacterial antigen on tumor cells to stimulate immune response.
- The study will evaluate IFx-2.0 plus pembrolizumab (Keytruda) vs placebo plus pembrolizumab.
The FDA has removed a manufacturing-related partial clinical hold on TuHURA Biosciences' phase 3 accelerated approval trial of IFx-2.0 in advanced or metastatic MCC. This regulatory action allows the company to proceed with the initiation and activation of clinical sites for the pivotal study.1
The trial, designated to operate under a Special Protocol Assessment (SPA) Agreement with the FDA, will investigate IFx-2.0 as an adjunctive therapy to pembrolizumab for the first-line treatment of advanced and metastatic MCC. Patients enrolled in the study will be randomized 1:1 to receive either IFx-2.0 plus pembrolizumab or placebo plus pembrolizumab.
The primary end point for the trial is overall response rate (ORR), with progression-free survival (PFS) as a key secondary end point. If achieved without a detrimental effect on overall survival, a successful PFS outcome could potentially satisfy the requirements for regular approval, bypassing the need for a post approval confirmatory trial, which is often a condition of accelerated approvals.
“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,” stated James Bianco, MD president and chief executive officer of TuHURA Biosciences, in a press release.
“The removal of the partial clinical hold allows TuHURA to begin the trial’s initiation and activation of clinical sites for the phase 3 accelerated approval trial of IFx-2.0,” continued Bianco in the press release.
MCC is a rare yet aggressive neuroendocrine skin cancer. While immune checkpoint inhibitors like pembrolizumab have significantly improved outcomes for these patients, a notable subset experiences primary resistance or disease progression.
IFx-2.0 is an innate immune agonist designed to overcome primary resistance to checkpoint inhibitors by enhancing the immune response against tumor cells. It is theorized to achieve this by inducing the expression of an immunogenic bacterial protein (streptococcal Emm55) on the surface of tumor cells, thereby activating innate immune cells and promoting the generation of tumor-specific T and B cells. Preclinical and phase 1b data have suggested that IFx-2.0 can "prime" the immune system, making tumors more susceptible to subsequent or concurrent immune checkpoint blockade.
“[IFx-2.0] is an intralesional product injected directly into 1 or more of the tumors that the patient has. It is designed to have a bacterial antigen from streptococcus bacteria and the transfection agent. When this gets in proximity to the cancer cells, the bacterial antigen starts expressing it on the cell surface. This should elicit an immune response from the body since it is a strong antigen. This draws the immune system in towards the tumor and, ideally, sparks an immune response,” said Andrew Brohl, MD, medical oncologist and physician-scientist at Moffitt Cancer Center, in an interview with Targeted OncologyTM.
The phase 3 trial is anticipated to enroll approximately 118 patients across 22 to 25 clinical sites in the US. Treatment with IFx-2.0 will involve weekly administration for 3 consecutive weeks, concurrent with the approved dosing schedule for pembrolizumab. Patients in both arms will receive pembrolizumab for up to 2 years or until disease progression or unacceptable toxicities.1,2 Clinical site activation and patient enrollment are expected to commence following this regulatory clearance.1
