Slide 1: Phase 3 trial of CAN-2409+prodrug with EBRT for newly diagnosed localized prostate cancer
Phase 3, randomized, placebo-controlled clinical trial of CAN-2409+prodrug in combination with standard of care external beam radiation (EBRT) for newly diagnosed localized prostate cancer Glen Gejerman, Andrea Manzanera, Thomas Wheeler, John Sylvester, Thomas Schroeder, Gregory Chesnut, Daniel Song
Slide 2: Disclosures
Disclosures Glen Gejerman, MD, MBA Co-Director of Urologic Oncology at Hackensack Meridian Health New Jersey Urology, Summit Health, Saddlebrook Consulting Agreement/ Speakers Bureau with Candel Therapeutics, Teleflex, and Novartis
Slide 3: Learning Objectives
Learning Objectives Attendees will learn about: • Topline efficacy and safety results for the investigational agent CAN-2409 in combination with standard-of-care EBRT for newly diagnosed localized prostate cancer. • CAN-2409 administration and how it fits into clinical practice. • Potential of CAN-2
Slide 4: Unmet need in localized prostate cancer
Unmet need in localized prostate cancer Global concern: approximately 1.4 million new cases of prostate cancer in 20201 Incidence in US2 INTERMEDIATE HIGH LOW RISK RISK RISK 65K 108K 43K Patients Currently Receiving Radiotherapy ~65K (~43%) 1 WHO cancer fact sheet. February 3, 2022 2 Globe Life Scie
Slide 5: CAN-2409 + prodrug: multimodal immunotherapy synergistic with radiotherapy
CAN-2409 + prodrug: multimodal immunotherapy synergistic with radiotherapy CAN-2409 induces formation of Valacyclovir Inflammatory Tumor CD8+ cytotoxic T cells mediators antigens Dendritic cell B-cell CAN-2409 locally administered Macrophage Fibroblast combined with oral prodrug Cytotoxic metabolite
Slide 6: Phase 3 clinical trial of CAN-2409 in newly diagnosed intermediate/high risk prostate cancer
Phase 3 clinical trial of CAN-2409 in patients with newly diagnosed, intermediate / high risk, localized prostate cancer NCT01436968 Primary Endpoints CAN-2409 + Valacyclovir N=745 (3 injection courses + radiotherapy, • Disease-free survival (time to cancer recurrence or death due to with or without
Slide 7: CAN-2409 is delivered in a routine and well-tolerated outpatient procedure
CAN-2409 is delivered in a routine and well-tolerated outpatient procedure Standard urologic injection procedure CAN-2409 biodistribution analysis Prostate Bladder Images of fluorescently labeled adenoviral vector in freshly resected prostate, demonstrating homogeneous distribution throughout the or
Slide 8: CONSORT diagram
CONSORT diagram Randomized 2:1 to CAN-2409 vs. placebo Reasons for incomplete treatment: Reasons for incomplete treatment: AE or complications 26 (5.2%), Lost to follow-up 1 (0.2%), AE or complications 15 (6%), Lost to follow-up 0 (0%), Patient choice 7 (1.4%), Physician choice 4 (0.8%) Patient choi
Slide 9: Demographics/baseline characteristics of randomized patients
Demographics/baseline characteristics of randomized patients CAN-2409 + prodrug Total ITT population (N=745) Placebo + prodrug (N=249) (N=496) (N=745) Median age (yrs) 69 68 69 Race, n(%) White/Caucasian 385 (77.6) 206 (82.7) 591 (79.3) Black/African American 93 (18.8) 28 (11.2) 121 (16.2) Asian 3 (
Slide 10: CAN-2409 in combination with SoC radiation +/-ADT was generally well tolerated
CAN-2409 in combination with SoC radiation +/-ADT was generally well tolerated Treatment related AEs >5% in either arm CAN-2409+prodrug Placebo+prodrug Total Preferred term • Chills, fever, flu-like symptoms were (N=479) (N=232) (N=711) commonly mild to moderate and self-limited Chills 160 (33.4) 20
Slide 11: Radiation therapy regimen
Radiation therapy regimen ~25% received moderate hypofractionated XRT EBRT, n (%) CAN-2409 Placebo Total Received RT 479 (100) 232 (100) 711 (100) Conventional RT (~78Gy in 2 Gy fractions) 341 (71.2%) 174 (75%) 515 (72.4%) Moderate hypofractionated (60 Gy in 3 Gy 123 (25.7%) 54 (23.3%) 177 (24.9%) f
Slide 12: CAN-2409 significantly improves disease-free survival (DFS)
CAN-2409 significantly improves disease-free survival (DFS) in newly diagnosed, intermediate/high-risk prostate cancer Hazard ratio (95% CI): 0.70 (0.52, 0.94), P=0.0155 Median follow-up: 50.3 months (CI 45.37, 51.29) CAN-2409 results in 30% improvement in DFS (includes death from any cause) compare
Slide 13: CAN-2409 significantly improves prostate cancer-specific DFS
CAN-2409 significantly improves prostate cancer-specific DFS Hazard ratio (95% CI): 0.62 (0.44, 0.87) P=0.0046 Highly significant 38% reduction in risk for prostate cancer recurrence or prostate cancer-related death (ITT*, n=745) Note: Disease-free survival (DFS) represents time to cancer recurrence
Slide 14: Prostate-specific outcomes stratified by ADT use or radiation regimen
Prostate-specific outcomes stratified by use of short-term androgen deprivation therapy (ADT) or radiation regimen Use of ADT Risk Category N events/ patients Prostate specific HR PrCa specific-DFS with CAN-2409 outcomes by RT regimen: No Androgen - Intermediate HR = 0.56 86/349 deprivation therapy
Slide 15: CAN-2409: other key secondary endpoints
CAN-2409: other key secondary endpoints • Significant increase in the proportion of patients achieving a prostate-specific antigen (PSA) nadir of <0.2 ng/ml in the treatment arm compared to the placebo o 67.1% vs. 58.6%, respectively (p=0.0164) • As expected*, overall survival was similar by treatme
Slide 16: CAN-2409 significantly improves pathological complete response in 2-year biopsies
CAN-2409 significantly improves the rate of pathological complete response in 2-year biopsies compared to the placebo control arm Pathological complete response was observed in 80.4% of the biopsies available at 2 years in the CAN-2409 arm compared to 63.6% in the placebo group CAN-2409 Placebo Tota
Slide 17: Positive biopsies ≥2 years after radiotherapy predict metastases and cancer-related mortality
Positive biopsies ≥ 2 years after radiotherapy are predictive of metastases and cancer-related mortality after long-term follow up Patients with a positive prostate biopsy ≥ 2 years after radiotherapy because of localized cancer had: • 10-fold higher odds of developing biochemical failure (P < 0.000
Slide 18: Concluding remarks
Concluding remarks • CAN-2409 significantly improved disease-free survival in patients with localized, intermediate- to-high-risk prostate cancer treated with standard-of-care EBRT with curative intent (HR 0.70; p = 0.0155) • CAN-2409 significantly improved prostate cancer-specific outcomes (HR 0.62
Slide 19: Acknowledgments
Acknowledgments Patients and their families, study site personnel, Dr. Peter Scardino for co-designing the trial. Investigators: Drs. Joshua Meeks, Nilay Gandhi, Steven Sukin, Ronald Tutrone, Michael Liss, Steven Kester, Maximiliano Sorbellini, Bryan Mehlhaff, Paul Kim, Shawn Zimberg, Stephen Savage