2018 ASCO Annual Meeting!
Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
Type: Oral Abstract Session
Time: Friday June 1, 2:45 PM to 5:45 PM
Molecular analysis for therapy choice (MATCH) arm W: Phase II study of AZD4547 in patients with tumors with aberrations in the FGFR pathway.
Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 2503)
Author(s): Young Kwang Chae, Christos Vaklavas, Heather H. Cheng, Fangxin Hong, Lyndsay Harris, Edith P. Mitchell, James A. Zwiebel, Lisa McShane, Robert James Gray, Shuli Li, S. Percy Ivy, Sherry Singer Ansher, Stanley R. Hamilton, Paul M. Williams, James V. Tricoli, Carlos L. Arteaga, Barbara A. Conley, Peter J. O'Dwyer, Alice P. Chen, Keith Flaherty; Northwestern University, Chicago, IL; University of Alabama, Birmingham, AL; University of Washington, Seattle, WA; Biostatistical Core, Harvard University, Boston, MA; Cancer Diagnosis Program, National Cancer Institute, Rockville, MD; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA; Cancer Therapy Evaluation Program, Bethesda, MD; National Cancer Institute, Bethesda, MD; Dana-Farber Cancer Institute, Boston, MA; National Cancer Institute at the National Institutes of Health, Rockville, MD; Regulatory Affairs Branch, CTEP, DCTD, NCI, Bethesda, MD; The University of Texas MD Anderson Cancer Center, Houston, TX; Frederick National Laboratory for Cancer Research, Frederick, MD; National Cancer Institute, Rockville, MD; Vanderbilt University Ingram Cancer Center, Nashville, TN; University of Pennsylvania Abramson Cancer Center, Philadelphia, PA; Early Clinical Trials Development Program, DCTD, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Massachusetts General Hospital, Boston, MA
Background: MATCH is a histology-agnostic signal finding trial targeting pathways in cancer. AZD4547 is a selective inhibitor of the fibroblast growth factor receptor (FGFR) 1-3 kinases. Methods: Patients (Pts) were screened by NGS for FGFR aberrations including amplification (≥7x), mutation, and fusion. 70/5558 (1.3%) of pts who underwent successful NGS evaluation were assigned to arm W. 52/689 (7.5%) of total pts enrolled in all treatment arms were in arm W (July 2016 to June 2017). 50 pts received treatment with AZD4547 80mg PO twice a day until progression of disease (PD) or drug intolerance. Results: 39/50 (78%) were female, 45/50 (90%) were Caucasian with a median age of 62 years (range: 22-80). 25/50 pts (50%) had received more than three prior lines of treatment. The most common histologies were breast (n = 16), urothelial (n = 7), and endometrial cancer (n = 4). Pts were divided into three groups: amplification (Amp) (n = 21), single nucleotide variant (SNV) (n = 20), or fusion (n = 9). Best confirmed response for the three groups are shown in the table below. Of 41 evaluable pts, the objective response rate was 5% (all partial response, PR), 51% stable disease (SD), and 44% PD. All pts with PR had tumors harboring FGFR fusions; one with urothelial transitional cell carcinoma (FGFR3-TACC3 F17T8) and the other with squamous cell carcinoma of cervix (FGFR3-TACC3 F17T11). Six cases [2 PR and 4 SD (2 SNV, 1 Amp, 1 fusion)] out of 41 achieved a duration of response greater than 24 weeks (disease control rate, 15%). The 6-month progression-free survival rate is 17% (90% CI: 8.6-34%): Amp 15% (90% CI: 4-58%), SNV 8% (90% CI: 2-38%), and fusion 42% (90% CI: 19-94%). Of 49 pts evaluable for adverse events (AEs), 39 experienced any AEs (80%) with 19 having grade 3/4 AEs (49%). Common AEs were fatigue, anorexia, dry mouth, nausea/vomiting, diarrhea, constipation, oral mucositis, anemia and liver function tests abnormality. Conclusions: AZD4547 demonstrated modest activity across various solid tumors with aberrations in FGFR pathway with acceptable toxicities. Further trials are warranted in tumors harboring FGFR fusions. Clinical trial information: NCT02465060