425: TuHURA Biosciences Initiates Phase 1b/2a Trial of IFx-Hu2.0 for Metastatic Merkel Cell Carcinoma

TuHURA Biosciences has commenced a Phase 1b/2a clinical trial to evaluate the safety and feasibility of IFx-Hu2.0 in combination with Keytruda for patients with metastatic Merkel Cell Carcinoma of Unknown Primary Origin.

Summary

• TuHURA Biosciences has initiated a Phase 1b/2a trial of IFx-Hu2.0 in combination with Keytruda for first-line treatment of metastatic Merkel Cell Carcinoma of Unknown Primary Origin (MCCUP).
• The trial aims to assess the safety and feasibility of IFx-Hu2.0 when administered via Interventional Radiology (IR) in patients with deep-seated tumors without associated cutaneous tumors.
• The Phase 1b/2a trial will enroll nine non-cutaneous MCC patients with hepatic, pulmonary, or retroperitoneal lesions, with three patients per lesion type.
• Each patient will receive IFx-Hu2.0 (0.1 mg) injected into a single visceral tumor weekly for three weeks, followed by pembrolizumab every three weeks for six months.
• The primary endpoint is safety and feasibility, evaluated 28 days after the last IFx-Hu2.0 dose.
• Secondary endpoints include efficacy per RECIST 1.1 criteria at three and six months.
• Data from the trial is expected by the end of Q4 2025 or early Q1 2026.
• TuHURA is also preparing to initiate a Phase 3 accelerated approval trial of IFx-2.0 with Keytruda versus Keytruda plus placebo in first-line treatment for advanced or metastatic MCC, anticipated to begin in Q2 2025.
• The FDA has agreed to allow the Phase 3 trial to be conducted under the accelerated approval pathway, using Objective Response Rate (ORR) as the primary endpoint.
• The FDA also suggested incorporating Progression Free Survival (PFS) as a key secondary endpoint, which could potentially eliminate the need for a post-approval confirmatory trial.

Sentiment

Score: 7

Explanation: The document presents a positive outlook with the initiation of a clinical trial and plans for a Phase 3 trial. The collaboration with the FDA and the potential for accelerated approval are also positive signals. However, the early stage of the trials and the inherent risks in drug development temper the overall sentiment.

Positives

• The initiation of the Phase 1b/2a trial expands the potential patient population who may benefit from IFx-Hu2.0 to include those with deep-seated tumors.
• The FDA's agreement to the accelerated approval pathway for the Phase 3 trial could expedite the approval process for IFx-2.0.
• The inclusion of Progression Free Survival (PFS) as a key secondary endpoint in the Phase 3 trial could lead to regular approval without a post-approval confirmatory trial.
• The trial design incorporates feedback from the FDA's Oncology Center of Excellence (OCE) and aligns with the FDA's Project Front Runner Initiative.

Risks

• The Phase 1b/2a trial is still in its early stages, and the safety and feasibility of IFx-Hu2.0 in combination with Keytruda for deep-seated tumors is yet to be fully established.
• The Phase 3 trial is subject to a partial clinical hold, which TuHURA believes it will meet the requirements to lift in Q2 2025.
• The success of the Phase 3 trial depends on achieving a statistically significant improvement in Objective Response Rate (ORR) and potentially Progression Free Survival (PFS).
• The development and commercialization of IFx-Hu2.0 are subject to regulatory risks, including the possibility that the FDA may not approve the drug or may require additional clinical trials.

Future Outlook

TuHURA anticipates initiating the Phase 3 registrational trial in Q2 2025 and expects data from the Phase 1b/2a trial by the end of Q4 2025 or early Q1 2026. The company is also focused on developing its Delta Opioid Receptor technology for other cancer therapies.

Management Comments

• James Bianco, M.D., President and Chief Executive Officer of TuHURA Biosciences, stated that the Phase 1b/2a trial may expand the potential number of addressable patients who may benefit from IFx-Hu2.0.
• Dr. Bianco added that if feasibility and safety are demonstrated, they plan to extend enrollment to a variety of non-MCC cancers that respond poorly to CPIs.
• Dr. Bianco believes that the mechanism of how IFx-Hu2.0 overcomes resistance to CPIs should be independent of the type of cancer treated.

Industry Context

This announcement is relevant to the immuno-oncology space, where companies are actively seeking to overcome resistance to checkpoint inhibitors like Keytruda. The trial's focus on patients with deep-seated tumors addresses an unmet need in Merkel Cell Carcinoma treatment. The collaboration with Keytruda (pembrolizumab) is a common strategy in the field to enhance the efficacy of existing therapies.

Comparison to Industry Standards

• The use of pembrolizumab (Keytruda) as a checkpoint inhibitor is a standard treatment in Merkel Cell Carcinoma, similar to approaches taken by companies like Merck, the manufacturer of Keytruda.
• The accelerated approval pathway sought by TuHURA is a common strategy for oncology drugs, mirroring the approaches used by other companies developing novel cancer therapies.
• The focus on overcoming CPI resistance aligns with the research and development efforts of numerous companies in the immuno-oncology field, such as Bristol-Myers Squibb and Roche.
• The trial design, including the use of RECIST 1.1 criteria for efficacy assessment, is consistent with industry standards for clinical trials in oncology.

Stakeholder Impact

• Positive impact on patients with metastatic Merkel Cell Carcinoma of Unknown Primary Origin (MCCUP) by providing a potential new treatment option.
• Potential benefit to shareholders through increased company value if the clinical trials are successful and IFx-Hu2.0 is approved.
• Opportunity for employees to contribute to the development of a novel cancer therapy.
• Collaboration with healthcare providers and research institutions to conduct the clinical trials.

Next Steps

• Enrollment and execution of the Phase 1b/2a clinical trial.
• Meeting requirements to lift the partial clinical hold on the Phase 3 trial in Q2 2025.
• Initiation of the Phase 3 accelerated approval trial in Q2 2025.
• Data analysis and reporting from the Phase 1b/2a trial, expected by the end of Q4 2025 or early Q1 2026.
• Continued development of the Delta Opioid Receptor technology.

Key Dates

Keywords

IFx-Hu2.0, Keytruda, Merkel Cell Carcinoma, MCCUP, Phase 1b/2a trial, Phase 3 trial, Immuno-oncology, TuHURA Biosciences, Checkpoint Inhibitors, FDA, Accelerated Approval, Pembrolizumab