Clinical Holds in Early Oncology Drug Development

Clinical holds in oncology are necessary to safeguard patients. Researchers are alerted to holds by news sources, but a systematic evaluation of clinical holds in early oncology drug development is lacking. Analysis of publicly disclosed clinical holds in oncology from 2016-2021 identified 39 holds. The majority (n=29) were for toxicity-related reasons, with fewer for chemistry, manufacturing and controls (CMC) (n=7) or other reasons (n=3). Toxicity-related holds took a median of 74 days till resolution, whereas chemistry, manufacturing and controls (CMC)-related holds took a median of 108 days to resolve. Acknowledging the limited sample size and scope of stock market conditions, toxicity-related clinical holds impacted the market value of small/medium sized biotechs by a median of -15%, which is far more than large biopharma (median 0%). These data suggest that toxicity-related clinical holds are common in early oncology and can have a more detrimental impact on small/medium sized biotech sponsors, the latter of which could have substantial financial repercussions, particularly in “biotech bear markets” where public investing in the sector has fallen out of favor (as in 2021-2022). ### Competing Interest Statement AS is an employee of Two River, Inc and owns shares in Allogene Therapeutics and Merck & Co., Inc., Rahway, NJ, USA. PSH is an employee of Foundation Medicine, Inc and owns shares in Roche, Bolt Therapeutics and TCR2. DD is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and owns shares in Merck & Co., Inc., Rahway, NJ, USA. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript.