Nonclinical work in oncology

Oncology programmes follow a different nonclinical framework from other therapeutic areas, and a sponsor who applies the general expectations will over-build the package. This article covers what changes, what the guidance says about choosing models, and where patient-derived models can be obtained in the United States.

Why the package is different

A dedicated guidance covers nonclinical evaluation for anticancer pharmaceuticals, and its stated purpose is to assist in designing an appropriate programme of nonclinical studies for these products.^[S1] The reasoning behind having a separate document is that the balance differs when the intended patients have advanced cancer and limited alternatives. Studies that would be required before clinical work for a chronic-use product may instead be required at the marketing application stage, and the extent of characterization expected before first dosing is narrower. Which studies this applies to is set out in the guidance and should be checked against it rather than assumed, because it varies by study type.

Choosing a model

The guidance is unusually direct about model selection. It states that appropriate models should be selected based on the target and the mechanism of action, and that the pharmaceutical need not be studied using the same tumour types intended for clinical evaluation.^[S2] That second clause removes a constraint sponsors often impose on themselves. A model carrying the genetic alteration the drug acts on is more informative than one matching the tumour type in the planned trial, and the guidance says so.

Where patient-derived models come from

Patient-derived xenografts are established by implanting human tumour tissue into immunodeficient mice, and a published review describes them as maintaining genomic characteristics of the original tumour.^[S4] In the United States the National Cancer Institute maintains a Patient-Derived Models Repository developed from human tumour tissues and blood,^[S3] which is a public source with documented provenance for the material. Commercial suppliers also hold collections; this site does not recommend any of them. What these studies measure is tumour growth in the model at a stated exposure. They do not predict how a patient will respond, and this article makes no such claim.

What to settle before placing the work

• {'items': ['Which guidance the study is designed against. For a product intended for patients with advanced cancer this is the oncology-specific document, and using the general framework instead produces a package larger than required.^[S1]', 'Whether the model carries the target. The guidance permits, and the science favours, selecting on mechanism rather than on tumour type.^[S2]', 'The provenance of the model. For patient-derived material, what consent it was collected under, what passage it is at, and what molecular characterization exists.', 'Which studies are exploratory and which support the submission, since efficacy pharmacology is normally conducted outside the good laboratory practice regulation while the safety studies are not.^[S6][S7]']}

Summary

Two things distinguish nonclinical work in this area. The package follows a guidance written for it, which changes when several studies are required rather than whether they are.^[S1] And model selection is explicitly permitted to follow the mechanism rather than the tumour type.^[S2] Both are checkable against the guidance before a study is commissioned.

About this article

This is an independent editorial article for people who commission nonclinical work in the United States. It does not discuss the efficacy of any product, approved or investigational, and it does not recommend any laboratory or model supplier. Guidance describes the agency current thinking and is not binding. Results in animal models describe the model; they do not establish what will happen in patients. Last reviewed: September 3, 2026.

References

1. FDA — ICH S9 Nonclinical Evaluation for Anticancer Pharmaceuticals, Guidance for Industry, March 2010. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/s9-nonclinical-evaluation-anticancer-pharmaceuticals (accessed 2026-09-03)
2. FDA — ICH S9, Section II.A, Pharmacology (description regarding model selection). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/s9-nonclinical-evaluation-anticancer-pharmaceuticals (accessed 2026-09-03)
3. NCI (National Cancer Institute) — Patient-Derived Models Repository (PDMR). https://pdmr.cancer.gov/ (accessed 2026-09-03)
4. Patient-derived xenograft model in cancer: establishment and applications. https://pubmed.ncbi.nlm.nih.gov/ (accessed 2026-09-03)
5. 21 CFR Part 58 — Good Laboratory Practice for Nonclinical Laboratory Studies (§58.1 scope). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-58 (accessed 2026-09-03)
6. 21 CFR 312.23(a)(8) — Requirements for Pharmacological and Toxicological Information to be Included in an IND. https://www.govinfo.gov/content/pkg/CFR-2023-title21-vol5/xml/CFR-2023-title21-vol5-sec312-23.xml (accessed 2026-09-03)