Abstract
Osimertinib (Osi) plus necitumumab (Neci) in EGFR-mutant NSCLC: An ETCTN California cancer consortium phase I study
Journal of clinical oncology, Vol.37(15_suppl), pp.9057-9057
05/20/2019
DOI: 10.1200/JCO.2019.37.15_suppl.9057
Abstract
Abstract only
9057
Background: Osi (3
rd
gen EGFR TKI) has robust activity in 1
st
line EGFR mutant NSCLC and TKI resistant T790M
pos
NSCLC but progressive disease (PD) occurs and outcomes with Osi alone are poor in T790M
neg
, C797X
pos
and EGFR exon 20 insertion (ins20) disease. This study examined the EGFR monoclonal antibody Neci with Osi in select settings of EGFR TKI resistance. Methods: Using a 3+3 design, Neci was examined in advanced EGFR mutant NSCLC at dose levels (DL) of 600 mg (DL1) & 800 mg (DL2) D1, D8 IV q21 days + Osi 80 mg qd. Four expansion cohorts (ExC; 18 each) included: A) T790M
neg
PD on 1
st
/2
nd
gen TKI as last therapy, B) T790M
neg
PD on 3
rd
gen TKI, C) T790M
pos
PD on 3
rd
gen TKI, D) EGFR ex20ins PD on chemotherapy. Central T790M testing by ddPCR in ExC A-C. Additional studies performed include: NGS panel of > 400 genes, EGFR FISH, plasma for PK and serial EGFR ctDNA by ddPCR as exploratory analyses. Adverse events (AEs) graded (Gr) by CTCAEv5 with ORR and PFS by RECIST 1.1. Results: Dose escalation and ExC B completed accrual. In total 55 pts were evaluable (Table). 1 pt had DLT at DL2, Gr 3 sinus bradycardia. Drug related Gr 3 AEs were seen in 27% (15) of pts, mainly rash (7;13%). ctDNA showed decreased mutant allele frequency with therapy in all pts studied with detected EGFR at baseline, with complete plasma clearance in a pt with detectable C797S. Conclusions: The RP2D (Osi 80 mg qd and Neci 800 mg D1, D8 IV on q21d cycle) is feasible and tolerable. In ExC A,T790M
neg
pts with 1
st
/2
nd
gen EGFR TKI as last treatment, using curtailed sampling, the pre-specified efficacy signal was reached for Osi + Neci comparing favorably to Osi alone in analogous pts from the AURA trial. Clinical activity was also seen in EGFR-dependent resistance (T790M
pos
C797S
pos
) after PD on 3
rd
gen TKI and in EGFR ins 20. Clinical trial information: NCT02496663. [Table: see text]
Details
- Title: Subtitle
- Osimertinib (Osi) plus necitumumab (Neci) in EGFR-mutant NSCLC: An ETCTN California cancer consortium phase I study
- Creators
- Jonathan W. Riess - University of California, DavisSusan G. Groshen - USC Norris Comprehensive Cancer CenterKaren L. Reckamp - City Of Hope National Medical CenterHeather A. Wakelee - Cancer Prevention Institute of CaliforniaGeoffrey R. Oxnard - Dana-Farber Cancer InstituteSukhmani Kaur Padda - Cancer Prevention Institute of CaliforniaMarianna Koczywas - City Of Hope National Medical CenterZofia Piotrowska - Massachusetts General HospitalLynette M. Sholl - Brigham and Women's HospitalCloud P. Paweletz - Dana-Farber Cancer InstituteChristie J. Lau - Dana-Farber Cancer InstituteJill Kolesar - University of KentuckyPhilip C. Mack - University of California, DavisJeffrey Moscow - National Cancer InstitutePasi A. Janne - Dana-Farber Cancer InstitutePrimo Lara - University of California, DavisEdward M. Newman - City Of Hope National Medical CenterDavid R. Gandara - University of California, Davis
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.37(15_suppl), pp.9057-9057
- DOI
- 10.1200/JCO.2019.37.15_suppl.9057
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 05/20/2019
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695785802771
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