The 3rd Stat4Onc Annual Symposium
Master protocols and seamless trials
Speaker Biography and Abstract
Nora C. Ku, M.D.
Ku, MD joined Loxo Oncology, Inc in September 2015 where she was responsible
for directing NAVIGATE, the phase 2 adult basket study of the selective TRK
inhibitor larotrectinib in patients with cancers harboring NTRK fusions. The results of this study contributed to FDA
accelerated approval in November 2018 of larotrectinib (Vitrakvi®), the first
drug to receive its initial approval simultaneously in adults and children and
for a tumor agnostic indication of NTRK fusion positive solid tumors. Nora continues as Executive Medical Director
for Loxo Oncology which was acquired in February 2019 by Eli Lilly and
is a native of Southern California and a graduate of the UCLA School of
Medicine. She completed her residency in
internal medicine at UT Southwestern/Parkland Memorial Hospital and her
fellowship in hematology/oncology at UCLA. She is board certified in internal
medicine and medical oncology. Nora has been active as a clinical investigator in private and
academic medical practice of hematology and oncology, overseeing the fellowship
training program and serving briefly as Chief of the Division of Hematology
Oncology at the University of California, Irvine. Just prior to joining Loxo Oncology, she
served as a medical director at Dava Oncology, LP, a group providing consultative services to
large and small pharmaceutical companies in their drug development
Protocols in Practice: Tumor Agnostic Approvals
FDA has granted 2 tumor agnostic approvals, the first in 2017 to Keytruda®
(pembrolizumab) for cancers characterized as MSI-h/dMMR and the second in 2018
to Vitrakvi® (larotrectinib) for cancers harboring a TRK gene fusion. These approvals reflect new approaches in
drug development using basket trial designs.
Clinical considerations in conducting such studies are presented.
Lingyun Liu, Ph.D.
Lingyun Liu got her Ph.D. in statistics from Northwestern University. She is
now a director in the strategic consulting team at Cytel. She has provided
consultation over 100 studies on clinical development plan, innovative trial
designs, regulatory interactions across different therapeutical areas including
oncology, immuno-oncology, diabetes, CNS, infectious diseases, cardiovascular
and rare disease and orphan drugs. She also supports DMC meetings with multiple
studies and provided instrumental guidance for interim decision making. Her
research interest includes multiple comparison, innovative design, rare
disease. She also provides technical inputs to the module development in the
commercial software EAST, StatXact.
Multi-Arm Multi-Stage Design
development of new therapies has been challenging due to high cost and failure
rate. More efficient trial design can save the time to market and achieve the
same objectives with less patients. There has been a shift from the traditional
clinical development paradigm to platform trials with the broad goal of finding
the best treatment for a disease by simultaneously investigating multiple
treatments in a seamless trial. This talk will discuss a commonly used platform
trial design--Multi-Arm Multi-Stage (MAMS) designs in the confirmatory setting.
Trials with MAMS designs are to compare several treatment arms to a common
control arm in multiple interim looks at which arms can be terminated either
for futility or overwhelming efficacy. This talk will present two approaches
for constructing such designs for preserving the familywise error rate (FWER).
Pairwise error rate control (PWER) and the context of its application will also
be discussed in contrast to FWER control. We will compare their operating
characteristics of the two approaches in various settings. We will also discuss
the challenges of designing such trials in the oncology setting.
Yihua (Mary) Zhao, Ph.D.
is currently Senior Principal Statistician at Boehringer Ingelheim. She has
extensive experience working as lead statistician in phase I through phase III
trials in oncology, respiratory and CNS. She was also the lead statistician for
several successful world-wide NDA submissions in oncology and respiratory and
participated in FDA advisory committee meetings to support the final approval
of NDA submissions. Her current research interests include master protocols,
Bayesian methods in clinical development, statistical challenges in pediatric
drug development and statistical methods for rare diseases.