Pembrolizumab (P) in patients (Pts) with colorectal cancer (CRC) with high tumor mutational burden (HTMB): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.
Eyal Meiri, Elizabeth Garrett‐Mayer, Susan Halabi, Pam K. Mangat, Sagun Shrestha, Eugene R. Ahn, Olufunlayo Osayameh, Venu Perla, Richard L. Schilsky
Abstract
133 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 CRC pts with HTMB treated with P are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-1, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had HTMB, defined as ≥9 mutations/megabase (Muts/Mb) by a FoundationOne test (n=26) or other tests (n=2) approved by the Molecular Tumor Board. Pts with MSI-H tumors were ineligible. Dosing of P was 2 mg/kg (n=8) or 200 mg (n=20) IV over 30 mins, every 3 wks. Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16+ wks according to RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight pts enrolled from June 2017 to November 2018; 1 pt was ineligible and excluded. HTMB ranged from 9 to 54 Muts/Mb. Table (N=27) summarizes demographics and outcomes. Tumor MS status was reported stable for 25 pts, ambiguous for 1 pt, and not available for 1 pt. One PR (MS stable and 10 Muts/Mb) and 7 SD16+ were observed for DC and OR rates of 28% (90% CI, 16% to 45%) and 4% (95% CI, 0% to 19%), respectively. 2 pts each had grade 3 AEs at least possibly related to P including abdominal infection, anorexia, colitis, diarrhea, fatigue, nausea, and vomiting; 1 also had SAE of acute kidney injury. Conclusions: Monotherapy with P showed anti-tumor activity in heavily pre-treated CRC pts with HTMB . Additional study is warranted to confirm the efficacy of P in this population. Clinical trial information: NCT02693535. [Table: see text]