Pertuzumab plus trastuzumab (P+T) in patients (pts) with solid tumors with ERBB2or ERBB3amplification (amp) or mutations (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

Abstract

3142 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pts with advanced solid tumors with ERBB2/3amp or mut treated with P+T 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 performed in CLIA-certified, CAP-accredited site selected labs. Dosing of P was 840 mg IV over 60 minutes (m), then 420 mg IV over 30-60 m Q3 weeks (wks); T was 8 mg/kg IV over 90 m, then 6 mg/kg IV over 30-60 m Q3 wks until disease progression. Low accruing histology-specific cohorts with ERBB2/3amp and/or mut were collapsed into 1 cohort for analysis. Primary endpoint was disease control (DC) per investigator defined as complete (CR) or partial (PR) response per RECIST v. 1.1, or stable disease (SD) of at least 16 wks duration (SD16+). The hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test (α= 0.10; 82% power based on alternative DC rate of 35%). Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response (OR), duration of response (DOR), duration of SD, and safety. DOR is time from documented OR to progressive disease (PD); duration of SD is time from tx start to PD. Results: 28 pts with 11 tumor types with ERBB2/3amp +/- mut (25) or mut only (3) were enrolled. The table shows demographics and outcomes. 2 CR (vagina, ERBB2amp, DOR= 151 wks; sweat gland, ERBB2amp, DOR= 48 wks), 6 PR (esophagus [2], small intestine, urothelial carcinoma [UC], site unspecified [SU], vagina; all with ERBB2amp) and 8 SD16+ (cervix [3], small intestine [2], UC, SU, testis; 6/8 pts had ERBB2 amp only, 1 had ERBB2mut only, 1 had ERBB3amp only) were observed for a DC rate of 57% (1-sided 90% CI: 43 to 100) and OR rate of 29% (95% CI: 13 to 49). The null hypothesis was rejected (p<0.001). Median duration of PR was 30 wks (range, 15-116, n=6). Median duration of SD for 8 pts with SD16+ was 28 wks (range, 18-84). 4/19 pts with KRAStesting performed had KRASalterations. 5 pts had ≥1 grade 3 tx-related adverse event (AE) or grade 2-5 serious AE: anemia, cardiac arrest resulting in death, diarrhea, ejection fraction decrease, pleural effusion, supraventricular tachycardia and vomiting. Conclusions: P+T showed antitumor activity in pts with advanced solid tumors with ERBB2/3amp. Additional study is warranted to confirm the efficacy of P+T in this population. Clinical trial information: NCT02693535 . [Table: see text]