Nivolumab monotherapy in patients with advanced platinum-resistant urothelial carcinoma: Efficacy and safety update from CheckMate 275.

Authors

null

Arlene O. Siefker-Radtke

The University of Texas MD Anderson Cancer Center, Houston, TX

Arlene O. Siefker-Radtke , Ari David Baron , Andrea Necchi , Elizabeth R. Plimack , Sumanta K. Pal , Jens Bedke , Yousef Zakharia , Marc-Oliver Grimm , Sergio Bracarda , Margitta Retz , Chikara Ohyama , Gary Grossfeld , Sandra Collette , Padmanee Sharma , Matt D. Galsky

Organizations

The University of Texas MD Anderson Cancer Center, Houston, TX, California Pacific Medical Center, San Francisco, CA, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Fox Chase Cancer Center, Philadelphia, PA, City of Hope National Medical Center, Duarte, CA, University Tübingen, Tübingen, Germany, University of Iowa, Iowa City, IA, Jena University Hospital, Jena, Germany, Azienda Ospedaliera S. Maria, Terni, Italy, Rechts der Isar Medical Center, Technical University of Munich, Munich, Germany, Hirosaki University, Hirosaki Aomori, Japan, Bristol-Myers Squibb, Princeton, NJ, Department of Medicine, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY

Research Funding

Pharmaceutical/Biotech Company

Background: In the open-label, single-arm, phase 2 CheckMate 275 trial, objective response rate (ORR) for patients (pts) with metastatic urothelial carcinoma (mUC) with nivolumab (NIVO) was 20.4% with minimum follow-up of 21.3 mo. Here, we report updated efficacy and safety data with minimum follow-up of 33.7 mo. Methods: Pts with platinum-resistant locally advanced or metastatic urothelial carcinoma received NIVO 3 mg/kg until disease progression or unacceptable toxicity. The primary endpoint was ORR by blinded independent review committee (BIRC) by RECIST v1.1 (including duration of response [DOR]). Secondary endpoints included progression-free survival (PFS) by BIRC, overall survival (OS), and ORR per investigator. Efficacy was evaluated in all treated pts and by tumor PD-L1 expression. Safety and PFS by investigator were exploratory endpoints. Results: ORR by BIRC was 20.7% (95% CI 16.1–26.1) including 18 (7%) complete responses (CR; with 1 additional CR since the last report; Table). ORR per investigator was similar (24.8%). Median DOR by BIRC was 20.3 mo (95% CI 11.5–31.3). Of 56 pts with best overall response (BOR) of CR or partial response (PR), 59% had a DOR ≥12 mo. Median PFS (mPFS) was 1.9 mo per BIRC (95% CI 1.9–2.3; Table) and 2.0 mo per investigator (95% CI 1.9–2.5). Median OS (mOS) was 8.6 mo (95% CI 6.1–11.3; Table). 12, 24, and 36-mo OS rates were 40%, 30%, and 22%. While efficacy was numerically higher in pts with tumor PD-L1 expression ≥1%, efficacy was observed in all pts (Table). Any-grade treatment-related adverse events occurred in 69% of pts (grade 3–4, 25%), mostly (59%) within the first 3 mo of initiating therapy. Conclusions: With long-term follow-up from CheckMate 275, NIVO continues to provide durable antitumor activity in pts with mUC. No new safety signals were noted. Clinical trial information: NCT02387996

All treated pts
N = 270
PD-L1 < 1%
N = 146
PD-L1 ≥1%
N = 124
ORR (95% CI)20.7 (16.1–26.1)16.4 (10.8–23.5)25.8 (18.4–34.4)
BOR by BIRC, n (%)
    CR18 (7)6 (4)12 (10)
    PR38 (14)18 (12)20 (16)
    Stable disease56 (21)24 (16)32 (26)
    Progressive disease111 (41)71 (49)40 (32)
mPFS by BIRC (95% CI), mo1.9 (1.9–2.3)1.9 (1.7–2.0)3.5 (1.9–3.7)
mOS (95% CI), mo8.6 (6.1–11.3)6.0 (4.4–8.1)11.9 (9.1–19.1)

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Genitourinary (Nonprostate) Cancer

Track

Genitourinary Cancer—Kidney and Bladder

Sub Track

Bladder Cancer

Clinical Trial Registration Number

NCT02387996

Citation

J Clin Oncol 37, 2019 (suppl; abstr 4524)

DOI

10.1200/JCO.2019.37.15_suppl.4524

Abstract #

4524

Poster Bd #

350

Abstract Disclosures