Abstract CT268: Palbociclib (P) in patients (pts) with solid tumors with CCND1 amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

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 CCND1 amp or mut treated with P are reported. Methods: Eligible pts had 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. Recommended dosing was one 125 mg capsule taken orally once daily for 21 days followed by 7 days off, until disease progression. Low accruing histology-specific cohorts with CCND1 amp or mut were collapsed into a histology-pooled cohort for analysis. Primary endpoint was disease control (DC) per investigator defined as complete (CR) or partial response (PR) or stable disease (SD) of at least 16 weeks (wks) duration (SD16+) per RECIST v1.1. The hypothesized null DC rate of 15% was rejected if the lower limit of a 1-sided 90% CI was >15%. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response (OR), duration of response (DOR) and SD, and safety. Results: 38 pts with 16 tumor types with CCND1 amp (n=36), mut (n=1) or both (n=1) were enrolled. 2 pts left before the 8-wk post-baseline tumor evaluation and were unevaluable for efficacy. Table shows demographics, outcomes and toxicity. 1 pt with CR (melanoma, PTEN Y155fs comutation, DOR= 111 wks), 1 with PR (melanoma, DOR= 9 wks) and 4 with SD16+ (prostate [2], bladder, bile duct) were observed for DC rate of 17% (1-sided 90% CI: 9 to 100) and OR rate of 6% (95% CI: <1 to 19). The null DC rate was not rejected. All pts with DC had CCND1 amp. 14 pts had ≥1 grade 3-4 tx-related adverse event (AE) or serious AE (SAE). Conclusions: P did not meet prespecified criteria for demonstrating activity in pts with solid tumors with CCND1 amp or mut. Table 1. Demographics (N=38); Efficacy Outcomes (n=36); Toxicity Outcomes (N=38) Median (Med) age, years (range) 66 (38-83) Female, No. (%) 15 (40) ECOG PS, No. (%) 0 9 (24) 1 23 (61) 2 6 (16) Prior systemic regimens, No. (%) 1 3 (8) 2 11 (29) ≥3 24 (63) Most common tumor types, No. (%) Head and neck 7 (18) Melanoma 5 (13) Esophageal 4 (11) Prostate 4 (11) Endometrial 4 (11) DC rate, % (OR and SD16+) (1-sided 90% CI) 17 (9, 100) OR rate, % (95% CI) 6 (<1, 19) Med PFS, wks (95% CI) 8 (6, 8) Med OS, wks (95% CI) 20 (15, 31) Med DOR (range), wks, n=2 9 and 111 Med duration of SD for pts with SD16+ (range), wks, n=4 33 (28, 48) Number of pts2 (%) with tx-related AE or SAEs AE3 14 (37) SAE4 4 (11) 1 Percentages may be >100% due to rounding2 Patients may have experienced one or more events3 Anemia, AST increase, lymphopenia, neutropenia, thrombocytopenia, leukopenia4 Febrile neutropenia, hyponatremia, neutropenia, thrombocytopenia Citation Format: Ramya Thota, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Tareq Al Baghdadi, Evan Pisick, Olatunji B. Alese, Herbert L. Duvivier, Ajjai S. Alva, Apar Kishor Ganti, Raghava R. Induru, Apostolia M. Tsimberidou, Mehmet Akce, Navid Hafez, Evthokia Hobbs, Andrew Riddle, Margaret von Mehren, Gina N. Grantham, Abigail Gregory, Dominique C. Hinshaw, Susan Halabi, Richard L. Schilsky. Palbociclib (P) in patients (pts) with solid tumors with CCND1 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 CT268.