FDA-AACR: Oncology Dose-finding Workshop
FDA-AACR: Oncology Dose-finding Workshop
June 13, 2016 | 8 a.m. - 5 p.m.
Walter E. Washington Convention Center, Washington, D.C.
Co-sponsored by the FDA and the AACR
Registration for this workshop is now
https://www.surveymonkey.com/r/DXLMB37
Since the approval of imatinib in 2001, the FDA has approved 26 small-molecule
kinase inhibitors for the treatment of oncology indications. Given the recent
history of approvals based on the results of early phase trials driven by
extraordinary efficacy data, the incentive for conducting rigorous dose-finding
trials may not be overtly apparent. However, the increasing need for the
development of combination therapy due to resistance to monotherapy and poor
tolerance of approved dosing regimens underscores the need for a more efficient
process of dose selection in the early stages of study design. Furthermore, the
unknown efficacy in light of frequent dose reductions in the post-market
setting begs the question of whether efficacy reported in early phase trials is
accurate when applied to a real-world population.
Objectives of the workshop
1. To identify key "best practices" in the nonclinical evaluation of a
compound, including, but not limited to: selectivity, pharmacology, secondary
pharmacology and toxicology.
2. To identify disease- and mechanism-specific nonclinical models better
able to predict efficacy.
3. To assess whether nonclinical information can be incorporated into the
statistical assumptions of an adaptive dose finding trial.
4. To discuss the "best practices" of integrating human pharmacokinetic and
pharmacometric data, including exposure-response analyses, into dose-finding
studies.
5. To assess how drug exposure can be integrated into the statistical
assumptions of an adaptive dose-finding trial and to assess whether evolving
exposure data can be adapted into an ongoing trial.
6. To shift from conducting a large, single-arm drug trial with the MTD
based on a 28-day window to identifying tolerable, biologically effective doses
for confirmatory trials through prudent search of doses based on safety,
efficacy and patient tolerability.
7. To discuss potential regulatory implications of dose-finding studies,
including but not limited to: product labeling of dose ranges, dose titration
and post-marketing studies.
Register for this https://www.surveymonkey.com/r/DXLMB37
A full agenda will be posted soon.
This workshop is a follow-up to the successful FDA-AACR public workshop:
Dose-finding of Small Molecule Oncology
http://www.aacr.org/AdvocacyPolicy/GovernmentAffairs/Pages/dose-finding-of-small-molecule-oncology-drugs.aspx,
which was held May 18-19, 2015. Full transcripts and select presentations
from that workshop are also available.