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2503 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. Amp SNV Fusion Total PR 0 0 2 2 SD 10 6 5 21 PD 7 9 2 18 Not Evaluable 4 5 0 9 Total 21 20 9 50
Chae et al. (Sun,) studied this question.