2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Oral Abstract Session
Time: Monday June 3, 8:00 AM to 11:00 AM
Location: Hall B1
Antitumor activity of TAK-788 in NSCLC with EGFR exon 20 insertions.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 9007)
Author(s): Pasi A. Janne, Joel W. Neal, D. Ross Camidge, Alexander I. Spira, Zofia Piotrowska, Leora Horn, Daniel Botelho Costa, Anne S. Tsao, Jyoti D. Patel, Shirish M. Gadgeel, Lyudmila Bazhenova, Viola Weijia Zhu, Howard West, Sylvie Vincent, Jian Zhu, Shuanglian Li, Gregory J. Riely; Dana-Farber Cancer Institute, Boston, MA; Stanford University and Stanford Cancer Institute, Stanford, CA; University of Colorado Cancer Center, Aurora, CO; Virginia Cancer Specialists, Fairfax, VA; Massachusetts General Hospital, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Beth Israel Deaconess Medical Center, Boston, MA; The University of Texas MD Anderson Cancer Center, Houston, TX; The University of Chicago Medical Center, Chicago, IL; University of Michigan, Ann Arbor, MI; University of California San Diego Moores Cancer Center, La Jolla, CA; University of California, Irvine School of Medicine, Orange, CA; Swedish Cancer Institute, Seattle, WA; Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA; Memorial Sloan Kettering Cancer Center, New York, NY
Background: TAK-788 is an oral investigational EGFR/HER2 inhibitor under evaluation in NSCLC patients (pts) with EGFR exon 20 insertions. We report results of a phase 1/2 open-label, multicenter study (NCT02716116). Methods: Pts with advanced, previously treated NSCLC received daily TAK-788 in dose escalation and expansion cohorts based on tumor genotype. Antitumor activity was determined for pts with EGFR exon 20 insertions who received TAK-788 at the RP2D. Safety is reported for all pts across all doses and at 160 mg. Results: As of 14 Sep 2018, 101 pts (median age, 61 y; female, 70%; ≥2 prior anticancer therapies, 76%; brain metastases, 53%) were treated with TAK-788 at 5–180 mg qd. RP2D was determined to be 160 mg. 28 pts with EGFR exon 20 insertions were treated with 160 mg qd during dose escalation or in expansion cohort 1 (median 3.6 mo on treatment; median 3.8 treatment cycles); 24 pts remain on treatment. Antitumor activity in pts with EGFR exon 20 insertions is shown in Table. At data cutoff, 7/14 responses were confirmed with 6 awaiting confirmation and 1 unconfirmed PR at 160 mg qd; median time to response in these 14 pts was 56 days. 23/24 evaluable pts with EGFR exon 20 insertions treated at 160 mg qd had decreased target lesion measurements (median best percent change, -32.6% [-79.1%, 3.8%]). Rate of treatment discontinuation due to AEs was 10.7% in pts treated at 160 mg. Most common TEAEs (≥20%) in pts treated with 160 mg qd: diarrhea (85%), rash (43%), nausea (41%), vomiting (30%), decreased appetite (28%), and stomatitis (22%); gr ≥3 TEAEs (≥5%) were diarrhea (26%) and hypokalemia, nausea, and stomatitis (7% each). Median dose intensity for pts treated with 160 mg qd was 93%. There is no clear trend that response to TAK-788 is enriched in particular EGFR exon 20 insertion variants. Conclusions: In NSCLC pts with EGFR exon 20 insertions, TAK-788 demonstrated antitumor activity and an AE profile consistent with other EGFR TKIs. Clinical trial information: NCT02716116
160 mg qd
n = 26a
|Best response (unconfirmed), n (%)b|
|Objective response, n (%)||14 (54)|
|Disease control, n (%)||23 (89)|
aPts with ≥1 disease assessment or discontinued due to AE. bBy RECIST v1.1. cSD observed ≥6 weeks after first study drug administration.