Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors: Long-term results of a large phase 1 study with multiple expansion cohorts.

2501 Background: DS-8201a is a HER2-targeted antibody drug conjugate with novel topoisomerase I inhibitor payload and linker technology. Methods: This ongoing phase 1 study (NCT02564900) enrolls subjects (sbj) with HER2+ breast cancer (BC) post T-DM1, HER2+ gastric cancer (GC) post trastuzumab, HER2 low BC (IHC 1+ or 2+, ISH-), and other HER2-expressing solid tumors (IHC ≥1+). Results: Results will be updated for presentation at meeting From Sep 2015–Dec 2017, 212 sbj received ≥1 dose of DS-8201a; 200 at 5.4 or 6.4 mg/kg. Median (mdn) age was 59 y with mdn of 4 prior regimens. At data cutoff, 121/200 (60.5%) sbj remain on treatment (tx). Mdn duration of tx was 10.3 mo (range 0.7+, 21.2+ mo). Overall, RECIST-confirmed overall response rate (ORR) in the evaluable sbj was 81/160 (50.6%) with the highest ORR in HER2+ BC (64.2%). Mdn duration of response was not reached (NR, range 0.03+, 15.2+ mo). 155/181 (85.6%) of sbj with ≥1 postbaseline scan (ps) experienced tumor shrinkage (92.3% of them at 1st ps at 6 weeks). Major reasons for tx discontinuation were progressive disease (PD; 50/200; 25.0%) and adverse event (AE; 18/200; 9.0%); 93/200 (46.5%) experienced a grade ≥3 AE. Common AEs included nausea 73.5% (3.5% grade ≥3), decreased appetite 59.5% (4.5% grade ≥3) and vomiting 39.5% (1.5% grade ≥3). Two grade 5 cases of interstitial lung disease were reported. Conclusions: DS-8201a shows antitumor activity in multiple tumor types with high ORR and durable responses in heavily pretreated sbj. Clinical trial information: NCT02564900. Confirmed ORR (95% CI)* DCR (95% CI) DOR, Mdn (95% CI), mo Duration of FU, Mdn Min, Max, mo PFS, Mdn (95% CI), mo OS, Mdn (95% CI), mo HER2+ BC 43/67, 64.2% (51.5, 75.5) 63/67, 94.0% (85.4, 98.3) 7.6 (NA) 6.0 0.7, 21.2 10.4 (NA) NR HER2+ GC 19/43, 44.2% (29.1, 60.1) 34/43, 79.1% (64.0, 90.0) 7.0 (NA) 5.6 1.2, 17.8 5.8 (3.0, 8.3) NR HER2 low BC 10/26, 38.5% (20.2, 59.4) 23/26, 88.5% (69.8, 97.6) NR 4.9 0.5, 16.1 13.6 (NA) NR Other HER2 expressing solid tumors 8/22, 36.4% (17.2, 59.3) 18/22, 81.8% (59.7, 94.8) NR 8.1 0.7, 15.0 NR NR *Sbj who received 5.4 or 6.4 mg/kg with 2 ps (N=141), or PD prior to 2nd ps (N=19), excluding 40 sbj too early to evaluate. Two low-HER2 GC sbj are not included in the Table; 1 had a confirmed response.