Page 3 - BladderCancerAbstracts

CANADIAN BLADDER CANCER FORUM 2023

Canadian Bladder Cancer Forum 2023 Meeting Abstracts – Podium

Presentations

Cite as: Canadian Bladder Cancer Forum 2023 Meeting Abstracts – Podium Presentations. Can Urol Assoc J 2023;17(3Suppl1):S1-3. http://dx.doi.org/10.5489/cuaj.8349

Phase 1 study of safety and immunogenicity of DPX-based products we profiled the proteome of MIBC treated with NAC to identify markers of
with or without intermittent low-dose cyclophosphamide in response and resistance to chemotherapy.
patients with non-muscle-invasive bladder cancer Methods: Pre-treatment tissue was included from 107 MIBC patients from
Alain Bergeron , Valérie Picard , Marjorie Besançon , Lisa D. MacDonald , two institutions who received NAC (including induction chemotherapy for
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Kabir Mody , Ashley Hilchie , Heather Hirsch , Lyne Lavoie , Stephan Fiset , cN1-3 MIBC) followed by RC. Residual tumor (≥ypT1N0-3M0-1) was pres-
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Yves Fradet 1 ent in the RC specimen in 66 (62%) patients after NAC, and was profiled
1 Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, for 55 (51%). Multiregional tumor sampling was conducted in 37/107
Canada; IMV Inc., Dartmouth, NS, Canada pre-NAC and 15/55 post-NAC samples. Benign ureter was used as con-
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Introduction: Intravesical chemotherapy or immunotherapy to prevent trol. Single-Pot, Solid-Phase-enhanced, Sample Preparation-Clinical Tissue
recurrences fail in a significant proportion of patients with non-muscle- Proteomics (SP3-CTP) was performed on formalin-fixed paraffin-embedded
invasive bladder cancer (NMIBC) and, therefore, more effective therapies tissue (FFPE), followed by bioinformatic analysis. Immunohistochemistry
are needed. The DPX platform is a versatile, non-aqueous, lipid-based (IHC) validation was conducted on matched tissues.
delivery platform that produces sustained T-cell responses against spe- Results: We quantified 9769 proteins across samples. Unsupervised clus-
cific peptide antigens. In ovarian cancer and DLBCL, it has been shown tering of pre-NAC tissue established four clusters based on biology and
to induce and maintain immune responses, leading to tumor regressions. survival outcomes, but with no difference in response by pathologic stage.
DPX-based immunotherapies targeting survivin and MAGE-A9, two tumor- Clusters were confirmed by IHC, and consisted of: Cluster 1 (CC1) with high
associated antigens expressed by NMIBC, could provide a novel way to metabolic activity and a luminal profile; Cluster 2 (CC2) with high nuclear
treat these tumors. activity; Cluster 3 (CC3) with high immune infiltration and basal profile;
Methods: This phase 1, multicenter study assesses the effect of three sub- and Cluster (CC4) with high immune infiltration and stromal signature. CC3
cutaneous injections, prior to transurethral resection (TUR), of 0.25 ml of showed worse survival outcomes (p<0.01). Multivariable analysis identified
DPX-based products (Q 3 weeks) ± intermittent low-dose cyclophospha- novel favorable (MAPK9 and MTIF3) and unfavorable (DVL2 and NES)
mide (CPA) as treatment for subjects with NMIBC who failed intravesical markers of survival. Matched analysis of pre- and post-NAC tissue showed
therapy. The primary objectives are to assess the safety and to evaluate markers (AZGP1 and ORM1) and pathways indicative of chemotherapy
induction of antigen-specific T-cell responses in ELISPOT assays. Additional resistance. In post-chemotherapy (i.e., resistant) tumors, we identified two
objectives include measurement of T-cell infiltration changes using multi- clusters: post-NAC Cluster 1 was enriched for nuclear processes and had
plex assays and number of patients achieving pT0 at TUR. Currently, arms worse outcomes, whereas post-NAC Cluster 2 was enriched for immune
using MVP-S (targeting survivin) and DPX-SurMAGE (targeting survivin and pathways. Multiregional proteomic analysis of histologically similar pre-
MAGE-A9) are enrolling subjects. NAC tissue revealed that highly heterogeneous tumors are enriched for
Results: As of January 2023, seven subjects have been enrolled: five have non-responders and have worse outcomes compared to homogeneous
received MVP-S ± CPA, one has received DPX-SurMAGE without CPA, tumor specimens. Moreover, comparative analysis of pre- and post-NAC
and four have completed TUR. Treatment has been well-tolerated, with matched tumors highlighted the importance of heterogeneity in chemore-
observations of grade 1 fatigue and injection site reactions. H&E staining sistance mechanisms.
of baseline and post-treatment TUR tumor samples has shown a marked Conclusions: We describe four pre-NAC and 2 post-NAC proteomic clusters
increase in immune cell infiltration in two of three post-MVP-S treatment with distinct biology and survival outcomes, alongside novel prognostic
specimens analyzed to date, suggesting local immune activity of MVP-S. biomarkers. Future work includes IHC validation of clusters in larger, inde-
Conclusions: Ongoing recruitment, soon with more participating centers, will pendent MIBC cohorts. A non-NAC cohort using pre-RC biopsy tissue will
allow more subjects to confirm these early observations, with more analyses be used to confirm the prognostic vs. predictive relevance of these findings.
of the anti-tumor activity of DPX products to be presented at the meeting. Funding: Bladder Cancer Canada, Deutsche Forschungsgemeinschaft
Proteomic profiling of muscle-invasive bladder cancer treated The predictive power of tertiary lymphoid structures in assessing
with neoadjuvant platinum-based chemotherapy reveals unique response to trimodal therapy in muscle-invasive bladder cancer
biologic clusters with clinical relevance Nour Hassan , José Joao Mansure , Mina Farag , Ronald Kool ,
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Alberto Contreras-Sanz , Gian L. Negri , Moritz J. Reike , Htoo Z. Eva Michaud , Mohammed Alessa , Luis Souhami , Fabio Cury ,
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Oo , Sandra E. Spencer Miko , Karina Nielsen , Morgan E. Roberts , Fadi Brimo , Wassim Kassouf 1,3
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Joshua Scurll , Kenichiro Ikeda , Gang Wang , Roland Seiler , 1 Cancer Research Program, Research Institute of the McGill University
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Gregg B. Morin , Peter C. Black 1 Health Centre, Montreal, QC, Canada; Division of Pathology, McGill
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1 Vancouver Prostate Centre, Department of Urologic Sciences, Vancouver, University Health Centre, McGill University, Montreal, QC, Canada;
BC, Canada; Canada’s Michael Smith Genome Sciences Centre, BC 3 Division of Urology, Department of Surgery, McGill University Health
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Cancer, Vancouver, BC, Canada; Department of Urology, Inselspital, Centre, Montreal, QC, Canada; Department of Radiation Oncology, McGill
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University of Bern, Bern, Switzerland University Health Centre, Montreal, QC, Canada
Introduction: Neoadjuvant cisplatin-based chemotherapy (NAC) followed Introduction: Radical cystectomy is the standard of care for muscle-invasive
by radical cystectomy (RC) is recommended for muscle-invasive bladder bladder cancer (MIBC). Radiotherapy (RT) is a bladder preservation option
cancer (MIBC); however, only ~40% of patients show an objective patho- that offers patients comparable survival rates. Despite appropriate selection
logic response, and the survival benefit is only 5–7% at five years. While criteria, up to 30% of patients will require salvage cystectomy. Emerging
DNA alterations and RNA classifiers may predict response to NAC in retro- evidence points to an important link between response to RT and the tumor
spective studies, the proteome has not been evaluated in this context. Here, microenvironment (TME). Notably, tertiary lymphoid structures (TLS) are
CUAJ • MARCH 2023 • VOLUME 17, ISSUE 3(SUPPL1) © 2023 CANADIAN UROLOGICAL ASSOCIATION S1