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
Clinical activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients (pts) with advanced RET-fusion+ non-small cell lung cancer (NSCLC).
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 9008)
Author(s): Justin F. Gainor, Dae Ho Lee, Giuseppe Curigliano, Robert Charles Doebele, Dong-Wan Kim, Christina S Baik, Daniel Shao-Weng Tan, Gilberto Lopes, Shirish M. Gadgeel, Philippe Alexandre Cassier, Matthew H. Taylor, Stephen V. Liu, Benjamin Besse, Michael Thomas, Viola Weijia Zhu, Hui Zhang, Corinne Clifford, Michael Palmer, Christopher D. Turner, Vivek Subbiah; Massachusetts General Hospital, Boston, MA; University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; University of Milano, European Institute of Oncology, Division of Early Drug Development, Milan, Italy; University of Colorado, Denver, CO; Seoul National University Hospital, Seoul, South Korea; Fred Hutchinson Cancer Research Center, Seattle, WA; National Cancer Center, Singapore, Singapore; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL; University of Michigan/Rogel Cancer Center, Ann Arbor, MI; Centre Léon-Bérard, Lyon, France; Oregon Health & Science University, Portland, OR; Georgetown University Medical Center, Washington, DC; Paris-Sud University, Orsay and Gustave Roussy, Villejuif, France; Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA; Blueprint Medicines Inc, Cambridge, MA; The University of Texas MD Anderson Cancer Center, Houston, TX
Background: RET fusions are targetable oncogenic drivers in up to 2% of NSCLC, yet no selective RET inhibitors are approved. BLU-667 is an investigational highly potent and selective RET inhibitor targeting oncogenic RET alterations, including those that confer resistance to multikinase inhibitors (MKIs). We provide an update on the registration-enabling ARROW study (NCT03037385) of BLU-667 in pts with RET-fusion+ NSCLC. Methods: The global ARROW study includes DE (30-600 mg daily [QD or BID]) and dose expansion (DX) at the recommended phase 2 dose (RP2D; 400 mg QD) in pts with advanced solid tumors. Primary objectives are overall response rate (ORR; RECIST 1.1) and safety. Results: As of 19Dec2018, 79 pts (21 DE, 58 DX) with advanced RET fusion+ NSCLC (44 KIF5B, 16 CCDC6, 19 other/pending) received BLU-667. Median number of prior therapies was 2 (range 0-8) and includes chemotherapy (76%), immunotherapy (41%), and MKI (27%). 39% had baseline brain metastases. ORR among 57 response-evaluable pts with measurable disease and at least one follow-up disease assessment was 56% (95% CI: 42, 69; 32 partial responses (PR), 9 PR pending confirmation, 20 stable disease, 5 progressive disease). 91% (29/32) of responding pts remain on treatment; 6 have achieved response duration ≥ 6 months. Disease control rate (DCR) was 91% (52/57). Among 30 pts at the RP2D previously treated with platinum chemotherapy, ORR was 60% (18 PRs; 7 pending confirmation). Responses occur regardless of prior treatment or RET fusion genotypes. Intracranial activity has been observed with shrinkage of brain metastases. 80% of NSCLC pts treated at RP2D remain on treatment and only 3% discontinued due to related adverse event. In NSCLC patients, treatment-related toxicity (TRT), generally low-grade and reversible (28% had ≥ grade 3 events), included increased AST (22%), hypertension (18%), increased ALT (17%), constipation (17%), fatigue (15%) and decreased neutrophils (15%). Conclusions: BLU-667 demonstrated potent, durable and broad antitumor activity and was well tolerated in pts with advanced RET-fusion+ NSCLC. Enrollment of the expansion is ongoing with registrational intent. Clinical trial information: NCT03037385