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Characterizing, Collecting, and Reporting Immune-Mediated Adverse Reactions in Cancer Immunotherapeutic Clinical Trials Draft Guidance for Industry; Availability October 2022

Draft Level 1 Guidance

Not for implementation. Contains non-binding recommendations.

Docket Number:
Issued by:
Guidance Issuing Office
Oncology Center of Excellence
Center for Biologics Evaluation and Research
Center for Drug Evaluation and Research

Cancer immunotherapeutic drugs and biological products (hereafter referred to as cancer immunotherapeutic drugs) can modulate (i.e., stimulate or suppress) the endogenous immune system to produce an anticancer effect. Adverse events that are consistent with an autoimmune etiology should be evaluated as potential immune-mediated adverse reactions (imAR) to guide patient management and inform the drug labeling or investigator brochure, as applicable.

For the purpose of this guidance, the term imAR refers to adverse reactions that occurred in the context of exposure to a cancer immunotherapeutic drug and are consistent with the development of an autoimmune reaction, and are not attributable to another cause (e.g., infection, trauma, other drugs). While corticosteroids and other immunosuppressive drugs are regularly used to manage imARs in cancer clinical trials, the absence of a history of immunosuppressive treatment for an adverse reaction does not preclude its characterization as an imAR, especially for low-grade imARs that result in dose interruption.

This guidance is intended for sponsors of cancer immunotherapeutic drugs that modulate the endogenous immune system and may disrupt immunologic tolerance to normal organs and tissues. Examples of such cancer immunotherapeutic drugs include monoclonal antibodies, anticancer vaccines, and cytokines. Adoptively transferred cell-based cancer immunotherapeutics that target a tumor-associated antigen (TAA) and directly exert an anticancer effect (e.g., a TAA-directed genetically modified T-cell immunotherapy) are outside the scope of this guidance.

This guidance provides recommendations regarding the data that should be collected and evaluated to assess whether adverse events qualify as imARs and the data on imARs that should be included in a new drug application (NDA) or biologics license application (BLA) for a cancer immunotherapeutic drug.

Submit Comments

You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))

If unable to submit comments online, please mail written comments to:

Dockets Management
Food and Drug Administration
5630 Fishers Lane, Rm 1061
Rockville, MD 20852

All written comments should be identified with this document's docket number: FDA-2022-D-1744.

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