Comment from Massive Bio, Inc

See attached file(s) Re: Docket No. FDA-2026-N-4390, "AI-Enabled Optimization of Early-Phase Clinical Trials Pilot Program; Request for Information" Dear Deputy Chief Medical Officer Mundkur and FDA colleagues: Massive Bio, Inc. appreciates the opportunity to respond to the Food and Drug Administration’s Request for Information on the proposed pilot program for AI-enabled optimization of early-phase clinical trials. We submit this comment one day after FDA’s landmark April 28, 2026 announcement of the Real-Time Clinical Trials (RTCT) initiative, which signals a paradigm shift from static, phased drug development toward continuous, AI-mediated trial learning systems. The convergence of the RTCT announcement, this RFI, and the broader regulatory architecture FDA has built—including the January 2025 draft AI credibility guidance, the NIST AI Risk Management Framework, Project Optimus, ICH E6(R3), and the April 2025 FHIR-for-RWD docket—creates a once-in-a-generation opportunity to redesign early-phase clinical development. Massive Bio is an AI-enabled precision oncology and clinical trial orchestration company focused on expanding equitable access to clinical trials and improving sponsor, site, clinician, and patient workflows. We submit this comment from the perspective of a company that has deployed AI-enabled trial matching, patient navigation, site and sponsor support, and real-world oncology data analytics at scale, while maintaining a human-in-the-loop model of clinician oversight. Our central recommendation is that FDA should design this pilot as a regulatory-grade, human-governed, AI-enabled trial orchestration program—not a narrow model evaluation or a sponsor-only operational experiment. The pilot should evaluate the full chain of early-phase trial performance: protocol parameterization, patient identification, biomarker assessment, site activation, enrollment, retention, safety signal detection, dose and cohort decision support, real-world evidence analytics, and Phase 1-to-Phase 2 evidence synthesis. It should do so in explicit alignment with the RTCT initiative’s vision of continuous, real-time trial data flows and with the April 2025 FHIR-for-RWD docket’s interoperability requirements. We have organized our comments by the categories and question numbers specified in the RFI. We also include a proposed reference architecture, a context-of-use ladder, a trustworthiness dossier, a metrics dictionary, and a new section addressing eight regulatory and operational gaps the RFI does not explicitly address but that the pilot must resolve to succeed. Respectfully submitted, Arturo Loaiza-Bonilla, MD, MSEd, FACP Co-Founder & Chief Medical AI Officer, Massive Bio, Inc. Selin Kurnaz, PhD Co-Founder & Chief Executive Officer, Massive Bio, Inc.