Abstract CT226: Crizotinib (C) in patients (pts) with solid tumors with MET amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

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 and MET amp or mut treated with C are reported.Methods: Eligible pts had no standard treatment (tx) options, had measurable disease, ECOG performance status (PS) 0-2, and adequate organ function. Pts with non-small cell lung cancer were excluded. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received C at 250 mg orally BID until disease progression. Low accruing histology-specific cohorts with MET amp or mut were collapsed into 1 histology-pooled cohort for analysis. Primary end point was disease control (DC) per investigator, 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 α= 0.10. Other end points were progression-free survival (PFS), overall survival (OS), duration of response and SD, and safety.Results: 31 pts with solid tumors (12 tumor types) and MET mut only (n=10), amp only (n=19), or mut and amp (n=1) were enrolled; 1 pt with overexpression was ineligible. 3 additional pts were unevaluable for efficacy. Table shows demographics and outcomes. 2 PR (both esophageal adenocarcinoma with MET amp) and 4 SD16+ (2 renal cell carcinoma, 1 with mut, 1 with amp; colorectal with amp; small intestine with amp) were observed for DC rate of 21% (1-sided 90% CI: 12%, 100%) and objective response rate of 7% (95% CI: 1%, 24%). The null DC rate was not rejected. 5 pts had ≥1 grade 3 tx-related adverse or serious adverse event.Conclusions: C did not meet prespecified criteria to declare a signal of activity in pts with solid tumors with MET amp or mut.Table: Baseline Characteristics (N=31); Efficacy Outcomes (n=28); Toxicity Outcomes (N=31) Median (Med) age, years (range) 61 (30, 82) Female, % 16 (52) ECOG PS, % 0 15 (48) 1 12 (39) 2 4 (13) Prior systemic regimens, % 1 3 (10) 2 5 (16) ≥3 23 (74) DC rate, % (OR and SD16+) (1-sided 90% CI) 21 (12, 100) Objective response rate, % (95% CI) 7 (1, 24) Med PFS, wks (95% CI) 8 (8, 13) Med OS, wks (95% CI) 37 (26, 68) Duration of response, wks (n=2) 14 and 20 Med duration SD, wks (n=4) 27 (26, 28) Number of pts1 with tx-related grade 3 adverse or any grade serious adverse event AE2 5 (16) SAE3 3 (10) 1Pts may have experienced one or more events 2ALT increase, diarrhea and all SAEs 3Acute kidney injury, ALT increase, AST increase, blood bilirubin increase, creatinine increase, dehydration, fatigue, GGT increase, hyperkalemia, nausea, sinus bradycardiaCitation Format: Kathryn F. Mileham, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Herbert L. Duvivier, Carmen J. Calfa, Carrie L. Dul, Alissa S. Marr, Eugene R. Ahn, Deepti Behl, Michael J. Hall, Inderjit Mehmi, Anu Gaba, Rom Leidner, Mark M. Zalupski, Gina N. Grantham, Abigail Gregory, Susan Halabi, Richard L. Schilsky. Crizotinib (C) in patients (pts) with solid tumors with MET 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 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 CT226.

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics