Abstract
Abstract Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors with PTEN mut treated with T are reported. Methods: Eligible pts had 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. After antihistamine pre-tx, 25 mg T was infused over 30-60 minutes once weekly until disease progression. Low accruing histology-specific cohorts with PTEN mut were collapsed into 1 histology-pooled cohort for analysis. Primary end point was disease control (DC), defined as complete or partial response (PR) or stable disease (SD) of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. The primary end point was summarized as a proportion and the hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test with alpha 0.10. Other end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), duration of SD and safety. DOR is defined as time from pt’s first documented objective response (OR) until progressive disease (PD). Duration of SD is defined as time from tx start to PD. Results: 34 pts with solid tumors (10 tumor types; 20/34 pts had prostate, soft tissue sarcoma [STS] or lung) with PTEN mut were enrolled. 6 pts were unevaluable for efficacy, 1 was ineligible. Table shows demographics, outcomes and toxicity. 2 pts obtained PR (prostate and STS) and 5 had SD16+ (lung, head and neck, breast, uterine, and site unspecified) for DC rate of 26% (1-sided 90% CI: 15.1%, 100%) and OR rate of 7% (95% CI: 1%, 24%). The null DC rate was rejected. Median PFS was 10 wks and median OS was 32 wks. Conclusions: T met prespecified criteria to declare a signal of activity in pts with solid tumors with PTEN mut. Table: Baseline Characteristics (N=34); Efficacy Outcomes (n=27); Toxicity Outcomes (N=34) Median (Med) age, years (range) 65 (42, 84) Female, % 14 (41) ECOG PS, % 0 13 (38) 1 18 (53) 2 3 (9) Prior systemic regimens, % 1 3 (9) 2 5 (15) ≥3 26 (77) DC rate, % (OR and SD16+) (1-sided 90% CI) 26 (15.1, 100) OR rate, % (95% CI) 7 (1, 24) Med PFS, wks (95% CI) 10 (7, 17) Med OS, wks (95% CI) 32 (13, 42) DOR, wks (n=2) 11 and 55 Med duration SD, wks (n=5) 27 (24, 36) Number of pts1 with tx-related grade 3-4 AE or SAE AE2 12 (35) SAE3 6 (18) 1Pts may have experienced one or more events 2alkaline phosphatase increase, anemia, chronic kidney disease, diarrhea, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, lung infection, oral pain and all SAEs 3acute kidney injury, dyspnea, generalized muscle weakness, hypophosphatemia, lung infection, oral mucositis, pericardial effusion Citation Format: Kristopher Wentzel, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Li Ding, Evan Pisick, Mridula Krishnan, Deepti Behl, Olatunji B. Alese, Carmen J. Calfa, Kathrine A. Cooper, Herbert L. Duvivier, Raghava Reddy Induru, Janet C. Ruzich, Song Zhao, Gina N. Grantham, Abigail Gregory, Susan Halabi, Richard L. Schilsky. Temsirolimus (T) in patients (pts) with solid tumors with PTEN mutation (mut): results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT231.
