Researchers Discuss Regulatory Considerations for Tissue-Agnostic Cancer Drugs

Posted 01 June 2017 By Michael Mezher

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In a paper set to be presented at the American Society of Clinical Oncology's annual meeting next week, three oncologists discuss some of the regulatory and scientific considerations for developing "tissue-agnostic" cancer treatments.

The paper, Tissue-Agnostic Drug Development, authored by oncologists Keith Flaherty from Massachusetts General Hospital's Cancer Center, Dung Le from the Sidney Kimmel Cancer Center at Johns Hopkins and Steven Lemery, a lead medical officer at the US Food and Drug Administration's (FDA) Office of Hematology and Oncology Products, comes just after FDA approved Merck's Keytruda (pembrolizumab) as the first tissue-agnostic cancer treatment in patients with solid tumors that have a specific biomarker.

Prior to this approval, FDA had only approved cancer drugs to treat tumors based on their location in the body, rather than solely based on a biomarker.

However, recent scientific and technological advances have shown there are numerous genetic mutations that are common in multiple cancer types, raising the possibility of developing drugs targeting those mutations irrespective of their location in the body.

"As the tools to unravel the molecular biology of cancer have enabled complete characterization of the hundreds of cases of all common cancers and many uncommon ones, it is clear that cancers arise from common somatic genetic building blocks," the authors write.

However, the authors caution that treatments targeting a specific mutation may perform differently against different tumor types.

"In the case of HER-2 [human epidermal growth factor receptor 2] amplified and BRAF mutant tumors, it has become clear that the spectrum of efficacy observed in one tumor type can vary substantially when comparing various cancer types harboring a specific genetic alteration," the authors write.

Accordingly, the authors say the decision to develop a tissue-agnostic cancer treatment should be backed by scientific rationale and made keeping the patient context in mind.

"For example, if a drug is most effective in combination regimens, tissue-agnostic development may not be appropriate given the differences in standard therapies administered to patients across tumor types," they write.

But if a drug-target combination appears to show "very high" or "breakthrough-like" activity across multiple tumor sites and can easily be demonstrated, the authors say that tissue-agnostic development may be appropriate.

The authors also say that sponsors will need to consider differences in the natural histories of patients with different cancers and how their studies will enroll a sufficient number of patients with different tumors.

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