FDA Releases Draft Guidelines for Organizing Uncertain Cancer Drugs

In 2017, Merck's PD-1 inhibitor pembrolizumab was approved for the treatment of microsatellite instable tumors; In 2018, Eli Lilly's TRK inhibitor larotrectinib was approved for the treatment of NTRK fusion tumors
.
These landmark events demonstrate the potential of
tissue-agnostic cancer drugs.
Recently, the FDA issued draft guidance for tissue-inconclusive cancer drugs, which will help approve drugs covering molecular mutations in multiple cancer types
.

The 13-page document released by the FDA details how
tissue uncertain cancer drug development differs from traditional drug development.
Drug developers need to generalize the treatment outcomes observed in some cancers to other tumors with the same molecular mutations, even if subjects with other cancers are not included in the development plan
.
The FDA believes that this outreach can be demonstrated
by a "strong scientific and clinical environment.
"

Key elements in the development process of tissue-uncertain cancer drugs include the biology of the target, the mechanism of action of the drug in different tumor types, the subject population, clinical pharmacology, safety, and efficacy characteristics
.
The draft guidance suggests that there may be cases where tissue-inconclusive cancer-like drugs may be more likely to be approved
.
For example, when a molecular mutation is very rare and expressed in a variety of tumors, uncertain cancer drug development strategies may be more feasible
.
The FDA also believes that if a mutation occurs in a specific or common tumor, sponsors need to first evaluate that it is more effective to develop drugs in this tumor environment (rather than in an uncertain carcinoid setting).

In September, the FDA's latest approved tissue indefinite cancer drug was Eli Lilly's RET inhibitor selpercatinib, which can be used to treat solid tumors
with RET gene fusion.
The drug was first approved in 2020 for the treatment of lung and thyroid cancers
with abnormal RET.
Earlier this year, the FDA also approved a combination of Novartis' BRAF and MEK inhibitors for the treatment of BRAF V600E mutated metastatic solid tumor
.

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