IFx-Hu2.0 plus pembrolizumab for advanced or metastatic Merkel cell carcinoma

IFx-Hu2.0 As An Adjunctive Therapy To Pembrolizumab In Checkpoint Inhibitor Naïve Subjects With Advanced Or Metastatic Merkel Cell Carcinoma

This will test whether injecting IFx-Hu2.0 into a visceral tumor together with pembrolizumab is safe and doable for adults with advanced or metastatic Merkel cell carcinoma who have not had prior immune checkpoint inhibitors.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: TuHURA Biosciences, Inc. (industry)
• Drugs / interventions: Pembrolizumab, avelumab, ipilimumab, nivolumab, chemotherapy, prednisone
• Locations: 2 sites (Tampa, Florida and 1 other locations)
• Trial ID: NCT06940440 on ClinicalTrials.gov

What this trial studies

This Phase 1, multicenter, open-label trial will enroll nine adults with recurrent or unresectable Stage III/IV Merkel cell carcinoma who are checkpoint inhibitor–naïve. Each participant will receive a single intralesional injection of IFx-Hu2.0 into a visceral lesion ≥3 mm followed by systemic pembrolizumab. The primary focus is on safety and feasibility, with imaging to document measurable disease and tumor tissue collection for biomarker analyses. Treatments will be administered at participating US cancer centers with scheduled follow-up for safety and response monitoring.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed recurrent or unresectable Stage III/IV Merkel cell carcinoma who are checkpoint inhibitor–naïve, have at least one visceral injectable lesion ≥3 mm, ECOG performance status <2, life expectancy ≥6 months, and adequate organ function are ideal candidates.

Not a fit: Patients who have received prior checkpoint inhibitor therapy, lack a visceral injectable lesion, have poor performance status, or have a life expectancy under six months are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, adding IFx-Hu2.0 to pembrolizumab could enhance anti-tumor immune responses in visceral MCC lesions and potentially improve response rates.

How similar studies have performed: Combining intratumoral immunotherapies with PD-1 pathway inhibitors has shown promising signals in other cancers, but intralesional IFx-Hu2.0 in Merkel cell carcinoma is early-stage and largely untested.

Eligibility criteria

Inclusion Criteria:

1. At least 18 years of age.
2. Life expectancy equal to or greater than six months.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status \< 2.
4. Active disease measurable by CT or MRI, measurable lesions are lesions that can be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded).
5. Must be recurrent and/or unresectable Stage III or Stage IV American Joint Committee on Cancer (AJCC) (8th edition) and have histologically confirmed Merkel cell carcinoma

   a. Must have at least one visceral injectable lesion equal to or greater than 3 mm
6. Subject should be CPI naïve i.e., no prior therapy with CPI including but not limited to Pembrolizumab, avelumab, ipilimumab, nivolumab.
7. Tumor tissue from an archival core biopsy or resected site of disease must be provided for biomarker analyses. If archival tissue is not available, then a new biopsy should be performed.
8. Adequate hematological, hepatic, and renal function according to laboratory ranges and medical criteria defined within the study protocol.

Exclusion Criteria

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with protocol requirements.
2. Subjects with active brain metastases, with the exception of treated brain metastases that have imaging proving stability at least 4 weeks after treatment, no new metastases, and not requiring steroids.
3. Subjects with recurrent resectable MCC
4. Subjects who have received prior systemic chemotherapy
5. Pregnant or breastfeeding females and females desiring to become pregnant or breastfeed within the timeframe of this study.
6. Active, known, or suspected autoimmune disease. Potential subjects with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. Low grade autoimmune toxicity is NOT an exclusion under this criterion.
7. A condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of IFx-Hu2.0 administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.

Where this trial is running

Tampa, Florida and 1 other locations

• H. Lee Moffitt Cancer Center and Research Institute — Tampa, Florida, United States (RECRUITING)
• University of Wisconsin Carbone Cancer Center — Madison, Wisconsin, United States (RECRUITING)

Study contacts

• Principal investigator: Andrew S Brohl, MD — Collaborator
• Study coordinator: James Bianco, MD

Conditions: Advanced Or Metastatic Merkel Cell Carcinoma, Metastatic, Advanced, Merkel Cell Carcinoma