# Replace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholds

Source: https://onco.cc/ideas/idea-tr1-pk-informed-organ-thresholds/  
OnCo record `idea-tr1-pk-informed-organ-thresholds` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Most trials copy the same kidney and liver cut-offs, such as creatinine clearance above 60, regardless of how the drug is cleared. Setting each threshold from the drug's own clearance route and organ-impairment pharmacokinetic studies would let patients with mild organ impairment join safely instead of being excluded.

## Summary

Organ-function eligibility criteria (creatinine clearance, bilirubin, transaminases) would be set per drug from its clearance route and the results of early organ-impairment pharmacokinetic studies, rather than the default 'creatinine clearance above 60 ml/min' copied between protocols. Drugs with negligible renal clearance would have no renal cut-off; drugs with hepatic clearance would have a dose-adjusted cohort instead of an exclusion.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Pharmacology-based thresholds will make at least 10-20 percent more patients eligible in older-skewed cancers without increasing dose-limiting toxicity, and will produce label dosing guidance for organ impairment at the time of approval rather than years later.
- Rationale: Renal impairment is common in patients over 70 and in myeloma, bladder and kidney cancer; many modern agents (monoclonal antibodies, most ADCs) are not renally cleared, so the criterion excludes without protecting. The FDA organ-dysfunction eligibility guidance supports this approach.
- Proposed test: A sponsor applies PK-informed thresholds across its oncology portfolio for two years and reports the eligible fraction, DLT rates and organ-impairment sub-cohort outcomes versus its historical protocols.
- Maturity: speculative
- Actor: industry

## Sources

- FDA: Eligibility Criteria: Patients with Organ Dysfunction or Prior or Concurrent Malignancies: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-patients-organ-dysfunction-or-prior-or-concurrent

## Connected records

- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/)
- bottlenecks: [Older and multimorbid patients are excluded and undertreated](https://onco.cc/bottlenecks/b-aging-comorbidity/), [Trials enrol too few, too slowly](https://onco.cc/bottlenecks/b-trial-enrolment/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)

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