The Citizen Petition That Reads Like Legislative History: ROS1/RET Meets the Precision Oncology Modernization Act

Last week, Reps. Jake Auchincloss (D-MA) and Morgan Griffith (R-VA) released the Faster Clinical Trials Act, which is intended to “speed the development of new treatments, invest in clinical research, and propel U.S. leadership in biomedical innovation.”  Deep inside the bill is a process to update cancer drug labels using genomic evidence to help identify patients who may not benefit from certain treatments.  Specifically, Title IV—Precision Oncology Modernization—seeks to establish a process for reviewing and updating the labeling of approved oncology drugs to reflect genetically defined subpopulations.  This bill would require the FDA Oncology Center of Excellence to identify oncology drugs for which there is new scientific evidence available pertaining to one or more actionable genetic alterations that is not reflected in the approved labeling of the drugs and establish a process to encourage voluntary labeling supplements—to be reviewed in 180 days—incorporating genomic exclusion criteria pursuant to the Agency’s section 505(o) authority.  “Genomic exclusion criterion” is defined as a labeling statement specifying that a drug is not indicated for, or should not be used in, patients whose tumors harbor a specific actionable genetic alteration for which an alternative approved targeted oncology therapy exists.

If this idea sounds familiar, you might have read our August 2026 blog post about a new Citizen Petition from Dr. Marc Matrana asking FDA to use its section 505(o)(4) authority to force updated scientific information into product labeling to keep drug labeling in step with science.  Specifically, Dr. Matrana asked FDA to direct a labeling change for a group of immunotherapies used to treat NSCLC and adopt a “Limitation of Use” to exclude patients whose tumors carry ROS1 or RET rearrangements so that these patients are redirected to targeted TKIs.   His theory is that recent NCCN Guidelines revisions reflect newly published clinical evidence not available at the time of the original immunotherapy approvals, demonstrating inferior outcomes and safety risks for ROS1- and RET-positive patients receiving first-line immunotherapy, and therefore qualify as “new safety information” under section 505(o)(4).  FDA has not yet responded to that Petition (granted, it’s only been four months), but this legislation ensures that FDA has the authority to do exactly what Dr. Matrana is asking.

The Matrana petition and Title IV of the Faster Clinical Trials Act are both responses to the same gap: FDA has clear authority to pare approved oncology indications down to the biomarker-defined subpopulations where the drug actually works, and clear precedent for doing so but no mechanism to do so, no standardized definition of a “genomic exclusion criterion,” no expedited supplement pathway, and no public registry.   The ad hoc 505(o)(4) route outlined in the Matrana petition is an unpredictable mechanism for something that will need to happen again and again as precision oncology matures.  In other words, if Title IV were law today, the Matrana petition arguably would not need to exist as a petition at all. It would be a stakeholder submission into the Section 403 Program, reviewed within 180 days of a complete supplement.

But for now, the Matrana petition is doing exactly what Section 403 is designed to institutionalize: identify an actionable genetic alteration, show that an approved targeted therapy exists, assemble mechanistic plus retrospective plus real-world evidence, and ask FDA to use 505(o) to narrow the immunotherapy indication.  It is a working example of what the Precision Oncology Modernization Act contemplates.