Pembrolizumab (P) in patients (pts) with metastatic breast cancer (MBC) with high tumor mutational burden (HTMB): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

person Ajjai Shivaram Alva University of Michigan, Ann Arbor, MI info_outline Ajjai Shivaram Alva, Pam K. Mangat, Elizabeth Garrett-Mayer, Susan Halabi, Ricardo H. Alvarez, Carmen Julia Calfa, Maged F. Khalil, Eugene R Ahn, Timothy Lewis Cannon, Pamela A. Crilley, Julie Gottlieb Fisher, Derrick S. Haslem, Sagun Shrestha, Kaitlyn R. Antonelli, Nicole L. Butler, Sasha L. Warren, Andrew Lawrence Rygiel, Shamika Ranasinghe, Suanna S. Bruinooge, Richard L. Schilsky

Authors person Ajjai Shivaram Alva University of Michigan, Ann Arbor, MI info_outline Ajjai Shivaram Alva, Pam K. Mangat, Elizabeth Garrett-Mayer, Susan Halabi, Ricardo H. Alvarez, Carmen Julia Calfa, Maged F. Khalil, Eugene R Ahn, Timothy Lewis Cannon, Pamela A. Crilley, Julie Gottlieb Fisher, Derrick S. Haslem, Sagun Shrestha, Kaitlyn R. Antonelli, Nicole L. Butler, Sasha L. Warren, Andrew Lawrence Rygiel, Shamika Ranasinghe, Suanna S. Bruinooge, Richard L. Schilsky Organizations University of Michigan, Ann Arbor, MI, American Society of Clinical Oncology, Alexandria, VA, Medical University of South Carolina, Charleston, SC, Duke University Medical Center, Durham, NC, Cancer Treatment Centers of America, Newnan, GA, Memorial Cancer Institute, Hollywood, FL, Lehigh Valley Hosp Network, Allentown, PA, Cancer Treatment Centers of America, Zion, IL, Inova Schar Cancer Institute, Fairfax, VA, Cancer Treatment Centers of America, Boca Raton, FL, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, Precision Genomics Program, Intermountain Healthcare, St. George, UT, Southwestern Reg Medcl Ctr, Tulsa, OK Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: TAPUR is a phase II basket study evaluating the anti-tumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. P is an immune checkpoint inhibitor and HTMB is an emerging predictive biomarker for checkpoint inhibitor therapy. Results in a cohort of MBC pts with HTMB treated with P are reported. Methods: Eligible pts had advanced cancer, no standard treatment options, ECOG PS 0-1, measurable disease and acceptable organ function. Genomic testing was performed using commercially available tests selected by sites. Pts matched to P had HTMB defined as ≥9 mutations/megabase (Muts/Mb) by a FoundationOne test (n=20) or approved by the TAPUR Molecular Tumor Board for other tests (n=8). A 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 weeks (wks) (SD16+)), an additional 18 pts are enrolled. If ≥7 of 28 pts have DC, the drug is considered worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight female MBC pts were enrolled from October 2016 to July 2018. Pts received P at 2 mg/kg (n=8) or 200 mg (n=20) IV over 30 minutes, every 3 wks. HTMB ranged from 9 to 37 Muts/Mb. Demographics and outcomes are summarized in Table (N=28). No relationship was observed between #Muts/Mb and PFS or OS. Two grade 3 AEs (weight loss and hypoalbuminemia) and 1 grade 2 SAE (urinary tract infection) were reported as at least possibly related to P. Conclusions: P demonstrated anti-tumor activity in heavily pre-treated MBC pts with HTMB . Additional study of P is warranted in MBC pts with HTMB. Clinical trial information: NCT02693535 Muts/Mb, median (range) 13 (9, 37) DC rate, % (OR or SD16+) (90% CI) 37% (24%, 46%) OR rate, % (CR or PR) (95% CI) 21% (8%, 41%) Median PFS, wks (95% CI) 10.6 (7.7, 21.1) Median OS, wks (95% CI) 31.6 (11.9, inf) Drug-related AEs, grades 3-4 (% of pts) 7% Drug-related SAEs, grades 3-4 (% of pts) 4% Median age, yrs (range) 63 (36, 78) ECOG Performance Status, % 0 36% 1 64% Prior systemic regimens, % 2 7% ≥3 93%