Deepa Arora: US FDA Guidance on Dose Optimization for Oncology Drugs

Deepa Arora, Chief Executive Officer at Clinexel Life Sciences Private Limited, shared on LinkedIn:

“Clinical Pharmacokinetic considerations – US FDA Guidance on Dose Optimization for Oncology Drugs.

In continuation with my previous post on this topic, here’re some of the key clinical pharmacokinetic (PK) considerations for dose selection for clinical trials specifically for Oncology drugs and drug development in general.

Dosages selected for administration in a clinical trial should be adequately supported by the relevant nonclinical and clinical data, e.g. activity against tumor, PK, PD, safety and tolerability.

Dosages selection should be adequately justified on the basis of the dose- and exposure-response relationships, taking utmost care that patients are not exposed to unreasonable and significant risk.

Where feasible, a Phase 1a/ dose finding trial with appropriate PK sampling plan to adequately characterize the PK (e.g., linearity, absorption, distribution, elimination) following the first dose and at steady-state can be particularly helpful for selecting appropriate dosage for efficacy focused trials.

Where a separate Phase 1a study is not feasible or unduly increases the timelines, a Master Protocol including multiple dosages/ drug combinations can be more appropriate.

Dosing strategies, such as a priming dose and intra-patient dose escalation/de-escalation, should also be explored in dose-finding trials when appropriate.

Population PK analyses are particularly important to identify intrinsic and extrinsic factors that can significantly impact the pharmacokinetics of a drug and therefore, dose selection.

Population PK should be initiated early and updated as additional data become available to identify specific populations in which the PK demonstrate clinically meaningful differences in exposure.”

Source: Deepa Arora/LinkedIn