FDA issues draft guidance on early-phase IND studies for solid tumors
The US Food and Drug Administration (FDA) has issued draft guidance to assist sponsors in developing early-phase first-in-human (FIH) studies for investigational drugs and biologics aimed at treating solid tumors as part of Operation TrialBlazer.
The draft guidance specifically addresses solid tumors and does not cover protocols for investigational drugs designed to treat hematologic malignancies.
According to a post on FDA’s LinkedIn page, the guidance “supports HHS’ Operation Trialblazer to maintain US leadership in early clinical research and development, along with the FDA Commissioner’s priority to accelerate cures by providing greater clarity to sponsors and investigators.”
Launched in mid-June, Operation TrialBlazer includes a set of initiatives aimed at accelerating the drug development process from the IND stage to late-stage clinical trials. This pilot program seeks to reverse the rising trend of clinical development shifting away from the US. (RELATED: HHS and FDA propose clinical trial reforms to expedite drug development, Regulatory Focus 23 June 2026)
The guidance covers several key aspects of early-phase clinical trials: determining eligibility, designing dose escalation trials, assessing early-phase studies with dose expansion cohorts, and assessing activity in early-phase trials. It also provides information on determining the appropriate dose for Phase 2 studies, Additionally, the guidance addresses the use of companion diagnostic devices that complement treatments, as well as strategies for collecting and analyzing data during the trials.
The guidance cautions that overly restrictive eligibility criteria may impede patient recruitment, limit access to early-phase trials, and result in trial outcomes that are not widely applicable to the patient population expected to use the drug.
Protocols should generally avoid imposing upper age limits. If an upper age limit is proposed, sufficient justification must be provided.
When designing a dose escalation trial, the guidance indicates that the primary objective for a FIH trial should focus on assessing safety and tolerability. Secondary objectives can include dose identification, pharmacokinetics, pharmacodynamics, immunogenicity, biomarker analyses, dose-exposure-response relationships, food effects, drug-drug interactions and preliminary measures of activity, such as response rates.
In early-phase studies that include dose expansion cohorts, the guidance emphasizes the importance of minimizing the number of subjects exposed to potentially ineffective drugs or those associated with significant toxicity. It states that the statistical analysis plan for these expansion cohorts should provide a justification for the maximum sample size.
In considering how to assess activity in early-phase trials, the guidance indicates that “single-arm trials do not adequately characterize endpoints like overall survival or progression-free survival.” In addition, a randomized study is “generally necessary” to evaluate time-to-event endpoints.
When considering companion diagnostic devices, the guidance indicates that it may be necessary to develop and validate an in vitro companion diagnostic device (CDx) if selecting patients based on biomarker assessments is essential for the safe and effective use of a drug. In these situations, it is advisable to consult with the Center for Devices and Radiological Health (CDRH) early in the clinical development process if a CDx needs to be created.
Stakeholders can comment on the guidance www.regulations.gov under docket no. FDA-2026-D-13432 until 11 January 2027.
Guidance, Federal Register notice
