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

3114 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of solid tumor pts with mTOR mutation (mut) treated with T are reported. Methods: Eligible pts had solid tumors, no standard treatment (tx) options, measurable disease, ECOG Performance Status (PS) 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts matched to T had various solid tumors with mTOR mut. After antihistamine pre-treatment, 25 mg T was infused over 30-60 minutes weekly until disease progression. Primary endpoint was disease control (DC), defined as complete (CR) or partial (PR) response, or stable disease at 16+ weeks (wks) (SD 16+) (RECIST v1.1). Low accruing histology-specific cohorts with the same genomic alteration and tx were collapsed into a single histology-pooled cohort for this analysis. For histology-pooled cohorts with sample size ≤28, the results are evaluated based on a one-sided exact binomial test with a null DC rate of 15% vs. 35% (α = 0.10 and power=0.86 for N = 26) and one-sided 90% confidence interval (CI). Other efficacy endpoint estimates are presented with two-sided 95% CIs. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts with solid tumors (11 histologies) with mTOR mut were enrolled from June 2016 to June 2020. 3 pts were not evaluable (2 pts, no post-baseline tumor eval; 1 pt, no measurable disease) and excluded from efficacy analyses. The Table shows demographics and outcomes. 2 PR and 10 SD16+ were observed for a DC rate of 46% (one-sided 90% CI: 32% to 100%) and an objective response (OR) rate of 8% (95% CI: 1% to 25%); the null hypothesis of a 15% DC rate is rejected (p<0.001). 5/10 pts with SD16+ had CRC or biliary cancer. Of the 2 pts with PR, one had uterine cancer and T1977R mut and the other had head and neck cancer and I1636V mut. The durations of PR were 12.3 and 23.9 wks, respectively, and median duration of SD was 34.5 wks (range: 18.7, 90.0) for pts with SD16+. 8 pts experienced grade 3 or grade 4 AEs or SAEs at least possibly related to T, including acute kidney injury, epistaxis, hyperglycemia, hypertension, hypertriglyceridemia, mucositis, leukopenia, thrombocytopenia, and pneumonitis. Conclusions: Monotherapy T showed evidence of anti-tumor activity in pts with advanced solid tumors with mTOR mut. Additional study is warranted to confirm the efficacy of T in pts with mTOR mut. Clinical trial information: NCT02693535. [Table: see text]