iMATCH Pilot: Immunotherapy Master Protocol

The iMATCH pilot, S2101 (aka the BiCaZo trial, for Biomarker Stratified CaboZantinib and NivOlumab), is rapidly approaching the launch pad and is expected to activate this summer.

The iMATCH master protocol will conduct centralized profiling of all participants using an assay platform that features two tests:

• whole exome sequencing, which will be used to calculate a tumor mutational burden (TMB) score and identify specific variants that may be treatable, and
• gene expression profiling, which will be used to generate a tumor inflammation score (TIS)

Once iMATCH is in high gear, these two tests will be used to prospectively identify which sub-studies screened patients should be enrolled to.

First, however, the team must run a pilot study to confirm that the iMATCH assay platform can be used in real time in this way. “Real time” in this context is defined as no more than 21 days between submission of a patient’s biopsy tissue and the delivery of test results to the patient’s oncologist in the clinic.

The S2101 pilot will also measure the efficacy of the cabozantinib + nivolumab treatment combination in patients with locally advanced or metastatic melanoma or head-and-neck cancer whose disease has progressed on previous checkpoint inhibitor treatment. One of the study’s primary endpoints is objective response rate in each disease cohort, across and within a matrix of four biomarker subgroups based on high or low TMB and TIS scores.

The pilot study will be run in two stages, separated by a temporary hold for a feasibility analysis.

In Stage 1, 60 patients will have their tissue tested for biomarkers, but they will not need to wait for the test results before beginning treatment. These first 60 patients will be assigned to their biomarker cohorts retrospectively.

In Stage 2, tumor tissue will again be analyzed centrally, but patients will be registered to the treatment step only if a slot is available in their biomarker cohort. Each of the four cohorts has a target registration of 30 patients overall.

This S2101 pilot study is chaired by Dr. Siwen Hu-Lieskovan, of Huntsman Cancer Institute at the University of Utah; Dr. Paul Sweicicki, of the University of Michigan; and Dr. Katerina Politi, of Yale Cancer Center. Drs. Hu-Lieskovan and Politi also, of course, chair the immunotherapeutics committee.

As S2101 will treat patients with melanoma or with head and neck cancer, it’s being developed in close cooperation with SWOG’s melanoma committee and (as we don’t have a head and neck cancer committee) our early therapeutics and rare cancers committee.

iMATCH is big news for SWOG. It’s our second master protocol (after Lung-MAP), with our third – MyeloMATCH – set to follow. I like our footprint in this space!