Nivolumab plus ipilimumab (N+I) in patients (pts) with ovarian cancer (OC) with BRCA1/2 mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

person Charles Drescher Swedish Cancer Institute, Seattle, WA info_outline Charles Drescher, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Deepti Behl, Eugene R Ahn, Tareq Al Baghdadi, R. Wendel Naumann, Maria C Bell, Charles A. Leath, Timothy Lewis Cannon, Olatunji B. Alese, Gina N. Grantham, Abigail Gregory, Dominique C. Hinshaw, Susan Halabi, Richard L. Schilsky

Authors person Charles Drescher Swedish Cancer Institute, Seattle, WA info_outline Charles Drescher, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Deepti Behl, Eugene R Ahn, Tareq Al Baghdadi, R. Wendel Naumann, Maria C Bell, Charles A. Leath, Timothy Lewis Cannon, Olatunji B. Alese, Gina N. Grantham, Abigail Gregory, Dominique C. Hinshaw, Susan Halabi, Richard L. Schilsky Organizations Swedish Cancer Institute, Seattle, WA, American Society of Clinical Oncology, Alexandria, VA, Sutter Sacramento Medical Center, Sacramento, CA, Cancer Treatment Centers of America – Chicago, part of City of Hope, Zion, IL, Michigan Cancer Research Consortium, IHA Hematology Oncology, Ypsilanti, MI, Levine Cancer Institute, Atrium Health, Charlotte, NC, Sanford Health, Sioux Falls, SD, O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham School of Medicine, Birmingham, AL, Inova Schar Cancer Institute, Fairfax, VA, Winship Cancer Institute of Emory University, Atlanta, GA, Duke University Medical Center, Durham, NC Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Bristol Myers Squibb, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Genentech, Merck, Pfizer, Seagen 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 OC with BRCA1/2 mut treated with N+I are reported. Methods: Eligible pts had advanced OC, measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was done in CLIA-certified, CAP-accredited labs. PD-L1 status was not routinely reported. Pts received I at 3 mg/kg every 3 wks for 4 doses with N at 1 mg/kg IV every 3 weeks (wks) for 4 doses. N alone was then continued at 240 mg every 2 wks or 480 mg every 4 wks until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete or partial (PR) response per RECIST v. 1.1, or stable disease of at least 16+ wks duration (SD16+). CA-125 levels were not routinely reported. Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled; otherwise, the cohort is closed. If ≥7 of 28 pts have DC, the null DC rate is rejected. P-value calculated based on 2-stage design. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: 33 pts with OC and BRCA1 (n=20), BRCA2 (n=10), or both mut (n=3) were enrolled from Sept 2017 to Oct 2019. 6 pts were not evaluable for efficacy analysis; 1 pt was found to be ineligible after enrolling, 5 pts discontinued tx before the post-baseline tumor evaluation due to an adverse or serious adverse event (SAE). Table shows demographics and efficacy outcomes. 6 pts with PR were observed for an OR rate of 22% (95% CI: 9% to 42%) and a DC rate of 27% (90% CI: 13% to 36%); the null hypothesis of a 15% DC rate was not rejected (p=0.17). 3 pts with PR had BRCA1 mut only, 2 pts had BRCA2 mut only and 1 pt had both BRCA1 and BRCA2 mut. Of the 6 pts with PR, 4 had microsatellite (MS) stable (MSS) tumors and MS status was not reported in 2. Of the 4 with MSS, 3 had a tumor mutational burden (TMB) ≤ 10 mutations per megabase and 1 had TMB of 11. 11 pts had at least 1 tx-related SAE, including acute kidney injury, ALT/AST increase, colitis, dehydration, diarrhea, E. coli, electrolyte disorder, fever, nausea/vomiting and pneumonitis. Conclusions: N+I did not meet prespecified criteria to declare a signal of activity in pts with OC and BRCA1/2 mut. However, given 22% of pts had PR (2 with >1 year duration) in this heavily pretreated cohort, additional study may be warranted to further evaluate efficacy. Clinical trial information: NCT02693535. Demographics (N=33) and efficacy outcomes (n=27). Median (Med) age, years (range) 59 (47-86) ECOG PS, % 0 25 (76) 1 7 (21) 2 1 (3) Prior systemic regimens, % 0-2 3 (9) ≥3 30 (91) DC rate, % (OR and SD16+) (90% CI) 27 (13, 36) OR rate, % (95% CI) 22 (9, 42) Med PFS, wks (95% CI) 8.1 (8.0, 8.3) Med OS, wks (95% CI) 45 (20, 133)

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