Nivolumab plus ipilimumab (N+I) in patients (pts) with solid tumors with high tumor mutational burden (HTMB): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

person John K Chan Sutter Cancer Research Consortium, San Francisco, CA info_outline John K Chan, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Timothy Lewis Cannon, Eugene R. Ahn, Paul Swiecicki, Evthokia Hobbs, Reza Nazemzadeh, Maria C Bell, Peter Joel Hosein, Funda Meric-Bernstam, Dominique C. Hinshaw, Abby Gregory, Gina N. Grantham, Susan Halabi, Richard L. Schilsky

Authors person John K Chan Sutter Cancer Research Consortium, San Francisco, CA info_outline John K Chan, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Timothy Lewis Cannon, Eugene R. Ahn, Paul Swiecicki, Evthokia Hobbs, Reza Nazemzadeh, Maria C Bell, Peter Joel Hosein, Funda Meric-Bernstam, Dominique C. Hinshaw, Abby Gregory, Gina N. Grantham, Susan Halabi, Richard L. Schilsky Organizations Sutter Cancer Research Consortium, San Francisco, CA, ASCO, Alexandria, VA, Inova Schar Cancer Institute, Fairfax, VA, City of Hope Chicago, Zion, IL, University of Michigan, Ann Arbor, MI, Providence Cancer Institute, Portland, OR, Levine Cancer Institute, Atrium Health, Charlotte, NC, Sanford Health, Sioux Falls, SD, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, Duke University Medical Center, Durham, NC Abstract Disclosures Research Funding Bristol Myers Squibb AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Genentech, Merck, Pfizer, Seagen, Taiho Oncology Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pts with advanced solid tumors with HTMB treated with N+I are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options or prior immune checkpoint inhibitor tx. PD-L1 expression testing was not required. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. HTMB was defined a priori as ≥9 mutations/megabase (Muts/Mb) via a qualifying test for TAPUR or approved by the Molecular Tumor Board. Pts received I at 3 mg/kg every 3 weeks (wks) for 4 doses with N at 1 mg/kg IV every 3 wks for 4 doses. N alone was then continued at 240 mg every 2 wks or 480 mg every 4 wks until disease progression. Low accruing histology-specific cohorts with HTMB were collapsed into 1 cohort for analysis. Primary endpoint was disease control (DC) per investigator defined as complete (CR) or partial (PR) response per RECIST v. 1.1, or stable disease (SD) of at least 16 wks duration (SD16+). The hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test (α= 0.10; 86% power based on alternative DC rate of 35%). Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response (OR), duration of response (DOR), duration of SD, and safety. DOR is time from documented OR to progressive disease (PD); duration of SD is time from tx start to PD. Results: 26 pts with 13 tumor types with HTMB were enrolled. Table shows demographics and outcomes. Tissue tumor mutational burden (TMB) ranged from 8 to 374 Muts/Mb (median= 16). 1 CR (small intestine; TMB= 48 Muts/Mb; DOR= 36 wks), 7 PR (biliary tract, site unspecified [3], soft tissue sarcoma, uterus, vagina; median TMB= 17 Muts/Mb; median DOR= 20 wks [range, 5-231]) and 1 SD16+ (pancreas; TMB= 26 Muts/Mb; duration of SD= 26 wks) were observed for a DC rate of 35% (1-sided 90% CI: 22 to 100) and OR rate of 31% (95% CI: 14 to 52). The null hypothesis was rejected (p=0.011). Notably, 1 pt (uterus, 374 Muts/Mb) is still on tx with an ongoing 66-wk PR as of Jan 2024. Most pts, including 8/9 with DC, were microsatellite stable. 10 pts had ≥1 grade 3 tx-related adverse event (AE) or serious AE. Conclusions: N+I showed antitumor activity in pts with advanced solid tumors with HTMB. Additional study is warranted to confirm the efficacy of N+I in pts with HTMB. Clinical trial information: NCT02693535. Demographics and efficacy outcomes (N=26). Median Age, yrs (range) 63 (37-86) ECOG PS, % 0 11 (42) 1 14 (54) 2 1 (4) Prior systemic regimens, % 0-2 17 (65) ≥3 9 (35) DC rate, % (OR and SD16+) (1-sided 90% CI) 35 (22, 100) OR rate, % (95% CI) 31 (14, 52) Median PFS, wks (95% CI) 9 (8, 18) Median OS, wks (95% CI) 53 (18, 127)

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