Advanced Or Metastatic Merkel Cell Carcinoma
Conditions
Keywords
Merkel Cell Carcinoma, Advanced, Metastatic, MCC, pembrolizumab, Innate Immune Agonist, Skin Cancer, X-Mark, X Mark, Rare Skin Cancers
Brief summary
This Phase 2/3, multicenter, randomized, double-blind, placebo-controlled trial will evaluate the Objective Response Rate (ORR) of IFx-Hu2.0 as an adjunctive therapy to pembrolizumab in adult participants (≥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 via intralesional injection in a single lesion, followed by pembrolizumab.
Interventions
DRUGIFx-Hu2.0
Therapeutic Classification: • Innate immune agonist Route of Administration: • Intralesional
DRUGPlacebo
Route of Administration: • Intralesional
DRUGPembrolizumab
Therapeutic Classification: • Immunotherapy (Immune checkpoint inhibitor) Route of administration: • Intravenous (IV) infusion
Sponsors
TuHURA Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. Participants 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. Participants with known active brain metastases with the exception of treated brain metastases that have imaging proving stability at least 4 weeks prior to the start of study treatment, no new metastases, and not requiring steroids. 3. Participants with recurrent resectable MCC 4. Participants 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 Participants 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) at 12 weeks and confirmed on a second response assessment at least 28 days after the initial response assessment, in the treatment arm based on BICR assessment according to RECIST v1.1. Confirmed response persisting at the time of response assessment, at approximately 24 weeks will constitute the data utilized for the endpoint analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 PD based on BICR assessment according to RECIST v1.1, or death, whichever occurs first. Participants without progression or death will be censored on the date of last disease assessment. |
Countries
United States
Contacts
CONTACTAmit Pande, MD
PRINCIPAL_INVESTIGATORAndrew S Brohl, MD
Collaborator
Outcome results
None listed