The immunoMATCH (iMATCH) pilot study, also known as the BiCaZO trial (S2101), is a phase II clinical trial investigating the combination of two immunotherapies—cabozantinib and nivolumab—in patients with advanced melanoma or squamous cell carcinoma of the head and neck (HNSCC), particularly those whose disease has progressed after prior checkpoint inhibitor therapy12345678.
Study Design and Objectives
• Combination Therapy:
o Cabozantinib is a tyrosine kinase inhibitor that blocks enzymes essential for tumor cell growth and angiogenesis.
o Nivolumab is a monoclonal antibody (immune checkpoint inhibitor) that helps the immune system recognize and attack cancer cells36.
• Patient Population:
o Adults with locally advanced or metastatic melanoma or HNSCC, including those who have not responded to previous immunotherapy236.
• Treatment Protocol:
o Nivolumab is given intravenously every 28 days, and cabozantinib is taken orally daily, for up to two years or until disease progression or unacceptable toxicity6.
• Biomarker Stratification:
o The study uses centralized molecular profiling of tumor tissue to classify patients based on two key biomarkers:
Tumor Mutational Burden (TMB): Measures the number of mutations within tumor DNA.
Tumor Inflammation Signature (TIS): Assesses the gene expression profile related to immune activity in the tumor microenvironment238.
o Patients are grouped into four cohorts based on high or low TMB and TIS scores.
Study Stages
• Stage 1:
o 60 patients receive treatment while their tissue is retrospectively analyzed for biomarker status.
• Stage 2:
o Patients are prospectively assigned to biomarker cohorts before starting treatment, with each cohort targeting 30 patients2.
• Feasibility Endpoint:
o The study aims to demonstrate that molecular profiling (TMB and TIS) can be completed and results delivered to clinicians within 21 days of biopsy submission28.
Primary and Secondary Endpoints
• Primary Endpoint:
o Objective response rate (ORR) in each disease and biomarker cohort (measured by tumor shrinkage or stabilization)28.
• Secondary Endpoints:
o Safety and tolerability of the combination therapy.
o Feasibility of real-time biomarker stratification.
o Correlation between biomarker status and treatment response238.
Significance
This trial is among the first to use a precision immunotherapy master protocol for advanced melanoma and HNSCC, integrating real-time molecular profiling to guide treatment. The results may help determine if specific biomarker-defined subgroups benefit more from the cabozantinib and nivolumab combination, potentially leading to more personalized and effective cancer therapy238.
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