Atezolizumab (atezo) with or without Bacille Calmette-Guérin (BCG) in patients (pts) with high-risk nonmuscle-invasive bladder cancer (NMIBC): Results from a phase Ib/II study.

Authors

Noah Hahn

Noah M. Hahn

Johns Hopkins Greenberg Bladder Center Institute, Johns Hopkins School of Medicine, Baltimore, MD

Noah M. Hahn , Gary D. Steinberg , Kelly Lynn Stratton , Ryan P. Kopp , Alexander Sankin , Eila C. Skinner , Kamal S. Pohar , Benjamin Adam Gartrell , Song Pham , Deepali Rishipathak , Sanjeev Mariathasan , Nicole N. Davarpanah , Corey Carter , Brant Allen Inman

Organizations

Johns Hopkins Greenberg Bladder Center Institute, Johns Hopkins School of Medicine, Baltimore, MD, NYU Langone Health and New York University School of Medicine, New York, NY, University of Oklahoma Health Sciences Center, Oklahoma City, OK, VA Portland Healthcare System and Oregon Health & Science University, Portland, OR, Montefiore Medical Center, Bronx, NY, Stanford University School of Medicine, Stanford, CA, Ohio State University, Columbus, OH, Hoffmann-La Roche Limited, Mississauga, Canada, Genentech, Inc., South San Francisco, CA, Duke Cancer Institute, Duke University, Durham, NC

Research Funding

Pharmaceutical/Biotech Company

Background: Standard treatment (tx) for high-risk NMIBC is transurethral resection of bladder tumor (TURBT) followed by BCG induction and maintenance. However, ≈50% of pts experience recurrence and/or progression after tx and may be ineligible for or refuse cystectomy. The PD-L1/PD-1 pathway may be involved with immune escape in NMIBC following BCG exposure. Here, we report results of atezo (anti?PD-L1) ± BCG in BCG-unresponsive, high-risk NMIBC. Methods: This multicenter study (NCT02792192) enrolled pts with BCG-unresponsive NMIBC with carcinoma in situ who had repeat TURBT. Cohort 1A and 1B pts received atezo 1200 mg IV q3w for ≤96 wk. Cohort 1B pts also received standard BCG induction (qw × 6 doses) and maintenance (qw × 3 doses at 3 mo), with optional maintenance courses at 6, 12, 18, 24, and 30 mo. For cohort 1B only, de-escalation was allowed for ≤3 BCG dose levels (full dose 50 mg, 66% and 33% of full dose). Co-primary outcomes were safety and complete response (CR) rate at 6 mo (6-mo bladder biopsy required). Duration of CR and 3-mo CR rate (key secondary outcomes) and 12-mo CR rate (exploratory) were also shown. Results: Cohorts 1A and 1B enrolled 12 pts each. Median age was 74 y; most pts had ECOG PS 0 (n = 7 [58%] in each cohort). At data cutoff (Sep 29, 2020), median atezo tx duration was 22.7 wk in cohort 1A and 31.6 wk in 1B. Following dose de-escalation in cohort 1B, the recommended BCG dose was 50 mg. BCG dose modification/interruption occurred in 4 pts (33%) due to an AE. The most common reason for tx discontinuation was disease recurrence or progression in both cohorts. Three pts (25%) in cohort 1A had atezo-related Gr 3 AEs (most common: maculopapular rash, n = 2); no atezo- or BCG-related Gr ≥3 AEs were seen in cohort 1B. Three dose-limiting toxicities occurred (1 [8%] in cohort 1A and 2 [17%] in cohort 1B), all reported as AEs of special interest. No Gr 4/5 AEs were reported. CRs, which appeared durable, were seen in both cohorts (Table). Conclusions: In this first report of atezo + BCG in NMIBC, atezo as mono- and combination therapy was well tolerated, with no new safety signals or tx-related deaths. Preliminary data suggested clinically meaningful activity, especially with atezo + BCG, requiring confirmation in a larger setting. Clinical trial information: NCT02792192.


Cohort 1A

Atezo
(n = 12)
Cohort 1B

Atezo + BCG (n = 12)
Cohort 1

total
(N = 24)
Best response, n (%)a



CR
4 (33)
7 (58)
11 (46)
Persistent or recurrent disease
7 (58)
4 (33)
11 (46)
Progressive disease
0
1 (8)
1 (4)
3-mo CR rate, n (%) [95%CI]
2 (17)
[2, 48]
5 (42)
[15, 72]
7 (29)
[13, 51]
6-mo CR rate, n (%) [95%CI]
4 (33)
[10, 65]
5 (42)
[15, 72]
9 (38)
[19, 59]
12-mo CR rate, n (%) [95%CI]
1 (8)
[0, 39]
5 (42)
[15, 72]
6 (25)
[10, 47]
Duration of CR (in pts with 6-mo CR), median (range), mo
6.8 (3.0-22.3*)
NE (13.8*-24.5*)
NE (3.1-24.5*)
No. of events, n (%)
2 (50)
0
2 (22)

* Censored. NE, not estimable. a Missing for 1 cohort 1A pt.

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Abstract Details

Meeting

2022 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Urothelial Carcinoma

Track

Urothelial Carcinoma

Sub Track

Therapeutics

Clinical Trial Registration Number

NCT02792192

Citation

J Clin Oncol 40, 2022 (suppl 6; abstr 493)

DOI

10.1200/JCO.2022.40.6_suppl.493

Abstract #

493

Poster Bd #

Online Only

Abstract Disclosures