Atezolizumab (A) plus pertuzumab/trastuzumab/hyaluronidase (PHESGO) in patients (pts) with solid tumors with ERBB2 alterations (alt): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

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. Results of a cohort of pts with solid tumors with alts treated with A+PHESGO are reported. Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no remaining standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited labs. Dosing for A was 1200 mg IV delivered every 3 weeks (wks). PHESGO was dosed every 3 wks, with a loading dose of 1200 mg/600 mg/30,000 units, then 600 mg/600 mg/20,000 units, until progression. Primary endpoint was disease control (DC) per investigator defined as objective response (OR) or stable disease (SD) of at least 16 wks duration (SD16+) per RECIST v.1.1. Simon 2-stage design tested null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2/10 pts in stage 1 had DC, cohort expanded to stage 2; otherwise, the cohort was closed. Cohorts closed prior to reaching the protocol-specified sample size of 28 used alternative thresholds set forth in the protocol to maintain the α level. For n=20, 6 pts had to have DC to reject the null (power = 0.74). Secondary endpoints were OR, progression-free survival (PFS), overall survival (OS), duration of response and SD, and safety. The cohort expanded to stage 2 but closed before reaching the planned sample size. 23 pts with 6 tumor types (colorectal [CRC; 14], gallbladder [GB; 3], stomach [3], breast [1], pancreas [1], small intestine [1]) with amplification (amp; n=16), overexpression (n=2), mutation (mut; n=2), and amp and mut (n=3) were enrolled. 3 pts were not evaluable. 2 partial responses (both GB, amp) and 2 SD16+ (both CRC, amp) were observed for a DC rate of 25% (1-sided 90% CI, 10 to 100) and an OR rate of 10% (95% CI, 1 to 32). The null hypothesis was not rejected (p=0.26). 6 pts had tx-related grade 3 AE/SAEs: acute kidney injury, ALP increase, dehydration, diarrhea, infusion related reaction, lymphopenia, maculo-papular rash, pneumonitis and sepsis. A+PHESGO did not demonstrate sufficient antitumor activity in pts with -altered solid tumors to warrant further study. However, the cohort did not reach its planned accrual, limiting statistical power for demonstrating efficacy. Other tx should be considered for these pts, including tx offered in clinical trials. .

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics