abstracts - Annals of Oncology

Annals of Oncology 25 (Supplement 4): iv511–iv516, 2014
doi:10.1093/annonc/mdu355.11
1473P
PHASE 1B TRIAL OF ANTI-NOTCH 2/3 ANTIBODY OMP-59R5
IN COMBINATION WITH ETOPOSIDE AND CISPLATIN (EP) IN
PATIENTS (PTS) WITH UNTREATED EXTENSIVE-STAGE
SMALL-CELL LUNG CANCER (ED-SCLC): THE PINNACLE
STUDY
M.C. Pietanza1, A. Spira2, R. Jotte3, S. Gadgeel4, A. Mita5, S. Liu6, W.L. Gluck7, G.
P. Kalemkerian8, A. Chiang9, L. Hart10, A. Kapoun11, L. Xu11, D. Hill11, L. Zhou11,
J. Dupont11, D.R. Spigel12
1
Medicine/thoracic Oncology, Memorial Sloan Kettering Cancer Center, New York,
NY, USA
2
Medical Oncology, Virginia Cancer Specialists, PC, Fairfax, VA, USA
3
Thoracic Oncology, Denver Divison, Rocky Mountain Cancer Centers, LLP,
Denver, CO, USA
4
Medical Oncology, Karmanos Cancer Center, Detroit, MI, USA
5
Oncology/Hematology, Cedars Sinai Medical Center, Los Angeles, CA, USA
6
Division of Hematology/oncology, Lombardi Comprehensive Cancer Center,
Georgetown University Medical Center, Washington, DC, USA
7
Clinical Trials Unit, Greenville Hospital System, Greenville, SC, USA
8
Division of Hematology/oncology, University of Michigan Medical School, Ann
Arbor, MI, USA
9
Medicine/medical Oncology, Yale University School of Medicine, New Haven, CT,
USA
10
Research Department, Florida Cancer Specialists, Fort Myers, FL, USA
11
Clinical Research, OncoMed Pharmaceutical, Redwood City, CA, USA
12
Sarah Cannon Research Institute, Tennessee Oncology PLLC, Nashville, TN,
USA
Aim: The Notch pathway plays a central role in embryonic development, the regulation
of stem and progenitor cells, and is implicated centrally in many human cancers,
including SCLC. OMP-59R5, a fully human IgG2 antibody, inhibits signaling of
Notch2 and 3 receptors. Anti-tumor activity was noted in 7 of 9 pt-derived SCLC
xenografts expressing Notch 2 and 3 with OMP-59R5 treatment. The maximum
tolerated dose (MTD) of single agent OMP-59R5 was 7.5mg/kg IV every 3 weeks
(Smith, EORTC 2012); the main dose-limiting toxicity (DLT) was Grade 3 diarrhea.
This study is to determine the MTD, pharmacokinetics (PK), pharmacodynamics
(PD), and preliminary efficacy of OMP-59R5 in combination with EP in ED-SCLC.
Methods: Cohorts of 3 to 6 pts were treated at each dose level of OMP-59R5.
OMP-59R5 was given IV on Day 1 of each 21 day cycle along with etoposide 100 mg/
m2 on Days 1, 2, and 3 and cisplatin 80 mg/m2 on Day 1. After 6 cycles, pts continued
OMP-59R5 alone every 21 days in the absence of disease progression or unacceptable
toxicities.
Results: By April 4, 2014, 11 pts were treated. One DLT of Grade 3 nausea was reported
from a subject in the 10 mg/kg dose cohort that lasted more than 48 hours despite daily
IV fluids and antiemetics. Frequently reported (≥30%) adverse events (all grades)
regardless of relationship were: fatigue (81.8%), nausea (72.7%), anemia (63.6%),
diarrhea (63.6%), decreased appetite (54.5%), weight loss (54.4%), hypomagnesemia
(45.5%), peripheral edema (45.5%), dehydration (36.4%), neutropenia (36.4%),
thrombocytopenia (36.4%), vomiting (36.4%) and elevated creatinine (36.4%). Of
these, fatigue (54.5%), anemia (36.4%), diarrhea (36.4%) and nausea (36.4%) were
considered related to OMP-59R5. The events were mostly Grade 1 or 2, and managed
with supportive care. Additional data are below:
Table: 1473P
OMP-59R5 Dose (mg/kg)
5 (n=3)
7.5 (n=3)
10 (n=5)
Etoposide (mg/m2)
Cisplatin (mg/m2)
DLT evaluable
incidence
RECIST 1.1 evaluable
Best Response/ Partial Response
Stable Disease
Progressive Disease
pts still on treatment
100
80
3
3
3
-
3
3
2
1
2
5
1
4
4
4
Conclusions: OMP-59R5 with EP is well tolerated. The MTD has not been reached.
Encouraging anti-tumor activity is observed. Updated safety, PK/PD, and efficacy data
will be presented. The Phase 2 part of PINNACLE will start in 2014.
Disclosure: A. Kapoun: Employed by OncoMed Pharmaceuticals (Sponsor), receive
salary and stocks; L. Xu: Employed by OncoMed Pharmaceuticals (Sponsor),
receive salary and stocks; D. Hill: Employed by OncoMed Pharmaceuticals (Sponsor),
receive salary and stocks; L. Zhou: Paid consultant for OncoMed Pharmaceuticals
(sponsor); J. Dupont: Employed by OncoMed Pharmaceuticals (Sponsor), receive
salary and stocks. All other authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
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abstracts
SCLC

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