Temsirolimus (T) in patients (pts) with solid tumors with PIK3CA mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

3117 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 cohorts of pts with breast cancer (BC) and other solid tumors with PIK3CA mut treated with T are reported. Methods: Eligible pts had BC or other solid tumors, 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. After antihistamine pre-tx, 25 mg of T was infused over 30-60 minutes once weekly until disease progression. Primary endpoint was disease control (DC), defined as complete or partial (PR) response, or stable disease of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. For the BC cohort, Simon’s optimal 2-stage design with null DC rate of 15% vs. 35% (power=0.85, α=0.10) was used with stage 1 (n=10) stopping for futility if < 2/10 pts had DC. Low accruing histology-specific cohorts with PIK3CA and T tx were collapsed into 1 histology-pooled (HP) cohort. For the HP cohort, the hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test with α=0.10. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: 12 pts with PIK3CA mut with BC and 29 pts with PIK3CA mut in other solid tumors (across 9 tumor types) were enrolled. 2 pts (1 in each cohort) were found to be ineligible after enrolling and were not included in efficacy analyses. Demographics and outcomes for each cohort are shown. At the end of stage 1 in the BC cohort, 1 PR was observed for DC and OR rates of 9%; the cohort was closed for futility (p=0.83). For the HP cohort, 3 PR and 5 SD16+ were observed for DC rate of 29% (p=0.049) and OR rate of 11%; the null hypothesis was rejected. Cancer types in pts with OR or SD16+ included cervical, ovarian and head/neck; most common muts were H1047R/L (3), E545K (2) and E542K (2). 1 pt with ovarian and H1047R has ongoing PR at 86 wks. 11/41 pts had ≥1 tx-related grade 3-4 adverse or serious adverse event, including anemia, headache, hyperglycemia, hypertension, hypertriglyceridemia, mucositis oral, lymphocyte, neutrophil or platelet count decrease, pneumonitis, and sepsis. Conclusions: Although T does not appear to have antitumor activity in pts with BC with PIK3CA mut, it does show antitumor activity in pts with other solid tumors with PIK3CA mut and warrants further study. Clinical trial information: NCT02693535 . [Table: see text]

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics