Abstract CT267: Temsirolimus (T) in patients (pts) with solid tumors with AKT1/3 amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study
Authors: Behl Deepti , Rothe Michael , Mangat Pam K. , Garrett-Mayer Elizabeth , Mackler Niklas , Duvivier Herbert L. , Gold Philip J. , Patel Sapna R. , Duffy Regan M. , Mauro Lauren A. , Ahn Eugene R. , Bell Maria , Calfa Carmen J. , Grem Jean L. , Rueter Jens , von Mehren Margaret , Grantham Gina N. , Gregory Abigail , Hinshaw Dominique C. , Halabi Susan , Schilsky Richard L. 
Published: April 2024

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 AKT1/3 amp or mut treated with T are reported.
Methods: Eligible pts had 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 pretreatment, 25 mg T was infused over 30-60 minutes once weekly until disease progression. Low accruing histology-specific cohorts with AKT1/3 amp or mut were collapsed into 1 histology-pooled cohort for analysis. Primary endpoint was disease control (DC) per investigator defined as complete or partial response or stable disease (SD) of at least 16 weeks (wks) duration (SD16+) per RECIST v1.1. 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), objective response (OR), duration of SD, and safety.
Results: 28 pts with solid tumors (14 tumor types; 13 pts had breast, ovarian or endometrial tumors) with AKT1 mut (n=25), AKT1 amp (n=1), both AKT1 amp and mut (n=1), or AKT3 amp (n=1) were enrolled. All pts were evaluable for efficacy. Table shows demographics, outcomes and toxicity. 4 pts with SD16+ (lung, breast, endometrial and ossifying fibromyxoid tumor) were observed for a DC rate of 14% (1-sided 90% CI: 6 to 100) and an OR rate of 0% (95% CI: 0 to 12). The null DC rate was not rejected (p=0.62). All 4 pts with DC had an AKT1 E17K mut. 5 pts had ≥1 grade 3 adverse events (AE) or serious AEs (SAE) at least possibly related to T.
Conclusions: T did not meet TAPUR’s prespecified criteria to declare a signal of activity in pts with solid tumors with AKT1/3 mut or amp.

Table 1. Demographics, Efficacy Outcomes, and Toxicity Outcomes (N=28) Median (Med) age, years (range) 66 (39-83) Female, No. (%) 22 (79) ECOG PS, No. (%) 0 12 (43) 1 12 (43) 2 4 (14) Prior systemic regimens, No. (%) 1 2 (7) 2 6 (21) ≥3 20 (71) DC rate, % (OR and SD16+) (1-sided 90% CI) 14 (6, 100) OR rate, % (95% CI) 0 (0, 12) Med PFS, wks (95% CI) 8 (6, 8) Med OS, wks (95% CI) 25 (14, 31) Med duration SD for patients with SD16+ (range), wks (n=4) 26 (18, 40) Number of pts2 (%) with tx-related AE or SAE (all grade 3) AE3 5 (18) SAE4 3 (11) 1 Percentages may be &gt;100% due to rounding2 Pts may have experienced one or more events3 Lymphocyte count decrease and oral mucositis4 Anorexia, fatigue, pericardial effusion, thromboembolic event
Citation Format: Deepti Behl, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Niklas Mackler, Herbert L. Duvivier, Philip J. Gold, Sapna R. Patel, Regan M. Duffy, Lauren A. Mauro, Eugene R. Ahn, Maria Bell, Carmen J. Calfa, Jean L. Grem, Jens Rueter, Margaret von Mehren, Gina N. Grantham, Abigail Gregory, Dominique C. Hinshaw, Susan Halabi, Richard L. Schilsky. Temsirolimus (T) in patients (pts) with solid tumors with AKT1/3 amplification (amp) or 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 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT267.