On September 14-15, 2021, the College of American Pathologists (CAP) and the American Society of Clinical Oncology (ASCO) hosted a virtual Immune Checkpoint Inhibition (ICI) Predictive Factor Summit. Thought leaders from key stakeholder segments participated, including the U.S. Food and Drug Administration (FDA), Centers for Medicare and Medicaid Services (CMS), National Institutes of Health (NIH), health insurance organizations, pharmaceutical companies, in vitro diagnostics manufacturers, and patient advocate organizations.

Aimed at addressing common issues of interest, the Summit provided an overview of current biomarkers for FDA-approved immunotherapies – Programmed Death-Ligand 1 (PD-L1) Immunohistochemistry (IHC), Microsatellite Instability/Mismatch Repair deficient (MSI/dMMR), and Tumor Mutation Burden (TMB) – and defined challenges in assay execution, interpretation, and clinical application.

Background

Advancement in ICI therapy for cancer is due greatly to the works of Drs. James P. Allison, PhD, MDACC, and Tasuku Honjo, MD, PhD, who were both awarded the Nobel Prize Award in 2018, as well as many other laboratories and clinical investigators whose tireless and innovative research has rapidly pushed the field forward. The clinical deployment of predictive factors for ICI therapy, including assessment of PD-L1 expression by immunohistochemistry (IHC) and determination of the likelihood of neoantigen expression using assays for mutational genotype (microsatellite instability) or tumor mutational burden, has been challenging for oncologists and pathologists alike. This circumstance has led to much confusion regarding ICI biomarker application, including the selection of specific assays and regulatory and reimbursement issues.

Objectives

• Examine the current state of FDA-approved biomarkers for selecting patients to receive immune checkpoint inhibitor therapy.
• Identify challenges and opportunities for improved access, clarity, and deployment of predictive factors for immune checkpoint inhibitors, especially those directed against the PD-1 and PD-L1 pathways.
• Discuss learnings that can facilitate the development of next-generation ICI biomarkers.
• Develop action plans for moving forward.

Highlights

• Sixty-eight people registered with 64 attendees on both days.
• Stakeholders from various perspectives gained insight into the analytical, clinical, and regulatory issues faced by these critical diagnostics.

Outcomes

• A joint ASCO/CAP manuscript will be developed from the proceedings
• Multiple working groups will consider recommendations for improving both the analytical validity of assays for these markers as well as revision of policies regarding their approval and reimbursement can be determined.

Watch recordings and presentations from the Summit on the CAP website. Scroll to the bottom of the page to see all videos and slides.