Placebo-Controlled Trial of IFx-Hu2.0 Followed By Pembrolizumab In Checkpoint Inhibitor Naïve Patients With Advanced Or Metastatic Merkel Cell Carcinoma

Phase 2

Not yet recruiting

• Conditions: Advanced Or Metastatic Merkel Cell Carcinoma
• Interventions: Drug: IFx-Hu2.0; Drug: Placebo; Drug: Pembrolizumab

• Registration Number: NCT06947928
• Lead Sponsor: TuHURA Biosciences, Inc.

Brief Summary

This Phase 2/3, multicenter, randomized, double-blind, placebo-controlled trial will evaluate Objective Response Rate (ORR) of IFx-Hu2.0 as an adjunctive therapy to pembrolizumab in adult patients (≥18 years) with advanced or metastatic Merkel Cell Carcinoma. A total of 118 participants will be randomized to receive either IFx-Hu2.0 or placebo intralesional injection in a single lesion, followed by pembrolizumab.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-14
• Study First Submitted QC: 2025-04-24
• Last Update Submitted: 2025-04-24
• Study First Posted: 2025-04-27
• Last Update Posted: 2025-04-27
• Study Start: 2025-06-30
• Primary Completion: 2027-03-31
• Study Completion: 2032-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 118

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. 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

   1. Must have at least one injectable lesion equal to or greater than 3 mm.
   2. Must have measurable disease as defined by RECIST v1.1.

5. Subject should be CPI naïve i.e., no prior therapy with CPI including but not limited to Pembrolizumab, avelumab, ipilimumab, nivolumab.

6. 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.

7. 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 with 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 randomization. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm	IFx-Hu2.0	Subjects randomized to the treatment arm will receive IFx-Hu2.0 (0.1 mg) intralesional injection in a single lesion once per week for three consecutive weeks. KEYTRUDA® (pembrolizumab) (200 mg) will be administered intravenously (IV) on Visit 1, then every three weeks until disease progression, unacceptable immune-related toxicities, or 2 years.
Treatment Arm	Pembrolizumab	Subjects randomized to the treatment arm will receive IFx-Hu2.0 (0.1 mg) intralesional injection in a single lesion once per week for three consecutive weeks. KEYTRUDA® (pembrolizumab) (200 mg) will be administered intravenously (IV) on Visit 1, then every three weeks until disease progression, unacceptable immune-related toxicities, or 2 years.
Control Arm	Placebo	Subjects randomized to the control arm will receive placebo intralesional injection in a single lesion once per week for three consecutive weeks. KEYTRUDA® (pembrolizumab) (200 mg) will be administered intravenously (IV) on Visit 1, then every three weeks until disease progression, unacceptable immune-related toxicities, or 2 years.
Control Arm	Pembrolizumab	Subjects randomized to the control arm will receive placebo intralesional injection in a single lesion once per week for three consecutive weeks. KEYTRUDA® (pembrolizumab) (200 mg) will be administered intravenously (IV) on Visit 1, then every three weeks until disease progression, unacceptable immune-related toxicities, or 2 years.

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	12 weeks post-treatment initiation and confirmed on a second response assessment at least 28 days after the initial response assessment	ORR is defined as proportion of subjects who achieve confirmed complete response (CR) or partial response (PR) at approximately 24 weeks assessed by blinded independent central review (BICR) following RECIST v1.1. Tumor response assessments will be performed at baseline and every 3 months for the first 24 months, thereafter every 6 months for up to 5 years.

Secondary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	up to 5 years	PFS is defined as the time (months) from the date of randomization to the date of the documented disease progression based on BICR assessment according to RECIST v1.1, or death, whichever occurs first. Subjects without progression or death will be censored on the date of last disease assessment.