Tucatinib + subcutaneous (SC) trastuzumab (Tuc + Trast SC) in patients (pts) with solid tumors with <i>ERBB2</i> alterations (alts): Results from the targeted agent and profiling utilization registry (TAPUR) study.

Abstract

3104 Background: TAPUR is a phase II basket study evaluating the antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alts. Combined results of four cohorts of pts with solid tumors with ERBB2 alts treated with Tuc + Trast SC are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was done in CLIA-certified, CAP-accredited labs. Dosing was 300 mg of Tuc given orally twice daily, 600 mg of Trast and 10,000 units of hyaluronidase SC every 3 weeks (wks), until disease progression. Primary endpoint was disease control (DC) per investigator definition as complete (CR) or partial (PR) response or stable disease (SD) of at least 16 wks duration (SD16+) per RECIST v.1.1. The hypothesized null DC rate of 15% was rejected if the lower limit of a 1-sided 90% CI was &gt;15%. Inferences were based on a beta-binomial model, which accounts for tumor type variance. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response (OR), duration of response, duration of SD (DOSD), and safety. Results: 78 pts (histology-pooled [n=40], lung [n=16], biliary tract [n=11], uterus [n=11]) with 21 tumor types with ERBB2 alts ( ERBB2 amplification [amp], n=38; mutation [mut], n=32; mut and amp, n=6; overexpression [OE], n=2) were enrolled. All cohorts were combined for analysis. 3 pts were not evaluable. Table shows demographics and outcomes. 1 CR (urothelial carcinoma [UC], ERBB2 mut), 6 PR (uterus [2], esophagus [1], lung, neuroendocrine [1], ovary [1], UC [1]; ERBB2 amp [5], mut [1]) and 18 SD16+ (10 tumor types; ERBB2 amp [7], mut [10], OE [1]) were observed for a DC rate of 33% (1-sided 90% CI, 27 to 100) and an OR rate of 9% (95% CI, 4 to 18). The null hypothesis was rejected. Duration of CR in 1 pt was 87 wks. Median (med) duration of PR was 12 wks (range, 6-72). Med DOSD in pts with SD16+ was 28 wks (range, 12-57). 20 pts (26%) had ≥1 grade 3 tx-related AE or SAE. All were consistent with tx label except back pain, cardiac troponin increase, chronic kidney disease, heart failure, hypomagnesemia, hypophosphatemia, pericardial and pleural effusion, peripheral motor and sensory neuropathy, sinus tachycardia, systemic inflammatory response syndrome and UTI. Conclusions: Tuc + Trast SC demonstrated antitumor activity in pts with advanced solid tumors with ERBB2 alts, warranting additional study. Clinical trial information: NCT02693535 . Demographics (N=78) and efficacy outcomes (n=75). Med age, years (range) 67 (39, 88) ECOG PS, No. (%) 0 29 (37) 1 44 (56) 2 5 (6) Prior systemic regimens, No. (%) 0-2 43 (55) ≥3 35 (45) DC (OR plus SD16+) rate, % (1-sided 90% CI), p-value 33 (27, 100) OR rate, % (95% CI) 9 (4, 18) Med PFS, wks (95% CI) 10 (8, 16) Med OS, wks (95% CI) 44 (30, 55)