ASCO 2022: Final Clinical Results of Pivotal Trial of IL-15RαFc Superagonist N-803 With BCG in BCG-Unresponsive CIS and Papillary Nonmuscle-Invasive Bladder Cancer

(UroToday.com) BCG therapy in non-muscle invasive bladder cancer induces cytokine release that activates NK and T immune cells and results in bladder cancer cell killing and immune memory against further tumor growth. It has been hypothesized that the IL-15 superagonist N-803 could boost the immune response to BCG, thus augmenting patient responses to BCG therapy and limit the need for cystectomy in this disease context.

 

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To validate this hypothesis in patients, Dr. Chamie presented results from the QUILT 3032 phase 2/3 study using the IL-15 superagonist N-803 in combination with BCG in previously BCG-unresponsive bladder cancer. The schema of the study is shown below, with a primary endpoint of complete response. There were two patient cohorts: Cohort A with carcinoma in situ +/- papillary tumors and Cohort B with papillary tumors only.

 

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The characteristics of patients enrolled on this study are shown below, notable for heavy pre-treatment with BCG and other therapies.

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Toxicities seen are illustrated below, with rare systemic side effects as would be expected from local intravesical therapy.

 

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In Cohort A (CIS +/- papillary tumors), the complete response rate to BCG + N=803 was 71%, with a median duration of response of over two years. Only 16% of patients went on to cystectomy and 100% of patients were alive despite their bladder cancer diagnosis at the data cut-off.

 

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There was no clear difference in clinical benefit when stratified by various subgroups, as shown below.

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Dr. Chamie then compared their results from cohort A to those from KEYNOTE-057, with the caveat that these are not head-to-head randomized comparisons. Overall, response rates and duration of response was higher, with similar and minimal toxicity with both treatment regimens.

 

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Dr. Chamie then shared results from cohort B of this study. Efficacy was similar across all tested subgroups (age, gender, race, T-stage, ECOG status).

 

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For concisce summary, Dr. Chamie shared the slides below:

 

Cohort A (CIS +/- papillary tumors)

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Cohort B (Papillary tumors)

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Dr. Chamie concluded that N-803 added clinically meaningful benefit to BCG in BCG-unresponsive NMIBC.

 

Presented by: Karim Chamie, MD, Department of Urology, University of California-Los Angeles

Written by: Alok K. Tewari, MD, PhD, medical oncologist at the Dana-Farber Cancer Institute, @aloktewar on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.

 

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