Background

The prevalence of hereditary prostate cancer (PCa) in the Netherlands appears lower than previously reported, and routine germline testing is not advocated as standard of care. Current referral strategies are based on a positive family history (FH) for high-risk penetrating cancer predisposition genes, on presence of metastatic disease (DISCOVER-study), or on a tumor-first approach in patients (pts) with castration-resistant PCa (CRPC) with cascade germline testing in those with an alteration in predefined genes. Here we compare referral based on FH with the tumor-first approach.

Methods

The PROMPT trial (NCT04746300) prospectively studies the impact of routine molecular tumor profiling with broad next-generation sequencing (NGS) in recently diagnosed CRPC pts. All results were discussed within the Radboudumc Molecular Tumor Board to guide precision medicine and for germline testing by geneticists per protocol. FH was taken at screening. The presence of familial and hereditary PCa by Dutch criteria for included pts was retrospectively assessed. High-risk homologous recombination deficiency (HRD) genes studied were BRCA1, BRCA2 and PALB2. Data on ATM and CHEK2 (lower-risk) will also be presented.

Results

In the 307 evaluable pts at least one pathogenic HRD alteration was found in 24 pts (8%), in BRCA1 (n=1), BRCA2 (n=21) and PALB2 (n=2) respectively. 17 pts (6%) were referred for germline testing; in 11 pts a germline variant was found. In 7/11 families the genetic predisposition was unknown, with pts not fulfilling Dutch referral criteria. FH was reported in 305 pts. Based on FH 53 pts would have been eligible for referral to clinical genetics and germline testing. In these pts, 48 pts did not have a pathogenic aberration in BRCA1/BRCA2 or PALB2 in tumor DNA.

Conclusions

Based on reported FH, 18% of the pts would meet the Dutch criteria for genetic testing. In the majority of them the chance of a germline mutation is estimated to be low based on tumor test results, and 7 families with a germline mutation would have been missed. A tumor-first approach for high risk genes led to referral of 6%, with a germline variant in 53% of pts. Routine tumor-first DNA testing in CRPC efficiently identifies pts eligible for germline testing.

Clinical trial identification

NCT04746300.

Legal entity responsible for the study

The authors.

Funding

VGZ - Betaalbaar Beter; Paul Speth Foundation; Radboud Oncologie Fonds; Radboudumc.

Disclosure

W.R. Gerritsen: Financial Interests, Institutional, Advisory Board: MSD, IMS Health, BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Research Grant: Bayer, Astellas; Non-Financial Interests, Principal Investigator: MSD, BMS. I.M. van Oort: Financial Interests, Sponsor/Funding: Astellas, Janssen, Bayer, MSD/AstraZeneca. M. Ligtenberg: Financial Interests, Institutional, Other: AstraZeneca, MSD; Financial Interests, Institutional, Advisory Role: AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Lilly, Merk Scharp & Dohme, Novartis, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb. N. Mehra: Financial Interests, Personal, Advisory Board: Pfizer, Roche, MSD, AstraZeneca, Astellas, JNJ; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Funding: Astellas, Pfizer; Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Institutional, Invited Speaker: BMS, Janssen, BMS; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS; Non-Financial Interests, Leadership Role, Head of the Prostate Cancer Working group: Dutch Uro-Oncology Study Group; Non-Financial Interests, Principal Investigator, Co-PI: Prospective Bladder Cancer Infrastructure (Netherlands); Non-Financial Interests, Leadership Role: Castration-resistant Prostate Cancer Registry. All other authors have declared no conflicts of interest.

Background

As previously reported, enza increases natural killer cells (NK) and decreases myeloid-derived suppressor cells (MDSCs) in biochemically recurrent (BCR) prostate cancer without ADT (Madan et al JITC, 2021). Enza’s immune impact in mCRPC with ADT has not been reported. This information could be important for developing new immunotherapy strategies in prostate cancer where PD1/PDL1 inhibition are not effective in unselected patients (pts).

Methods

Pts with mCRPC who had progression on ADT alone were randomized to either enza or enza+prostvac(P), a therapeutic cancer vaccine targeting PSA. Pts were followed for time to progression (TTP). Peripheral blood was assessed at baseline and at 1 month for 10 parental cell types (CD4+ and CD8+ T cells, T-regulatory cells, NK, NK-T cells, conventional and plasmacytoid dendritic cells, B cells, monocytes, and MDSCs) and 148 refined subsets related to their maturation/function. Serum IL-8 cytokine levels were also evaluated.

Results

57 pts were enrolled. The median age of all pts was 57 years (47-94) and median PSA was 15.02 (0.55-587). Median TTP was 23.3 months for all pts, with no differences between the arms. 24 pts were evaluated for immune responses: 12 with enza alone, and 12 with enza+P. Pts treated with enza had trends of increases in NK cells (n=12, p=0.064) and increases in MDSC (p=0.042) at 1 month vs baseline. With enza alone, increases in subsets of monocytes and MDSCs were associated with shorter TTP. With enza+P, increases in NK after 1 month were also seen (p=0.064), and greater increases in PD-L1+ mature NK were associated with longer TTP. No changes or associations with TTP were seen among T-cells, B-cells or dendritic cells. Among all pts, IL-8 decreases at one month were associated with longer TTP.

Conclusions

Enza in first-line treatment of mCRPC with ADT was associated with increased NK and MDSC; drops in IL-8 levels were associated with better TTP. This compares to enza in BCR without ADT where NK were also increased, but MDSC were decreased, and IL-8 was unchanged. NK which have been associated with better outcomes in prostate cancer are increased after enza in mCRPC and these findings could inform future immunotherapy strategies.

Clinical trial identification

NCT01867333.

Legal entity responsible for the study

Clinical Center, National Cancer Institute.

Funding

EMD Serono.

Disclosure

All authors have declared no conflicts of interest.

Background

We previously reported a trial of a DNA vaccine encoding prostatic acid phosphatase (PAP, pTVG-HP) with pembrolizumab in patients with metastatic, castration-resistant prostate cancer. The current trial evaluated a similar approach in patients with earlier stage prostate cancer, without evidence of metastases (nmCSPC).

Methods

Patients with nmCSPC were treated with pTVG-HP and nivolumab every 2 weeks for 12 weeks, and then every 4 weeks, for 1 year total. Patients were then followed an additional year off treatment. The trial was designed as a single-arm 2-stage phase 2 trial with the primary endpoints being safety and complete PSA response rate. Secondary objectives included immune evaluations, 2-year MFS, median rPFS, and changes in PSA.

Results

No patients achieved a complete PSA response, and the trial was stopped after 19 patients were accrued to the first phase. Treatment was without unexpected toxicity. Median PSA doubling time (DT) pre-treatment was 5.9 months, and significantly increased (25.6 months, p=0.001) during the 12-month treatment period. PSA DT decreased in the 1-year post-treatment period (14.2 months). 3 patients (16%) had PSA declines from baseline > 50%, and 5 (26%) had PSA declines > 25%. 8/19 (42%) patients developed PAP-specific IFNγ- and/or granzyme B-secreting T cells, which tended to occur in patients with favorable change in PSA DT. While long-term follow up continues for several patients, with a median follow-up time of 13.8 months, 2 patients (11%) have had radiographic progression within 2 years.

Conclusions

PD-1 pathway inhibitors alone have demonstrated little clinical activity for prostate cancer. Our findings demonstrate that combining PD-1 blockade with the T-cell activating agent pTVG-HP is safe, and can augment tumor-specific T cells that can result in prolonged stable disease. The absence of complete PSA responses, and the finding that PSA rise recurred after treatment, suggest that either longer therapy, or additional treatments, are required to optimize response. Ongoing and planned trials are assessing vaccines encoding multiple target antigens and/or using combined T-cell checkpoint blockade.

Clinical trial identification

NCT03600350.

Legal entity responsible for the study

Douglas G. McNeel, MD PhD.

Funding

University of Wisconsin Carbone Cancer Center.

Disclosure

D.G. McNeel: Financial Interests, Personal, Ownership Interest: Madison Vaccines Inc.; Financial Interests, Institutional, Principal Investigator: BMS, Novartis, Harpoon Therapeutics, Janssen; Financial Interests, Personal, Advisory Role: CellVax. H. Emamekhoo: Financial Interests, Personal, Advisory Board: Exelixis, Seattle Genetics. J. Eickhoff: Financial Interests, Personal, Advisory Role: AbbVie, Amgen, Bluebird Bio, AIQ. G. Liu: Financial Interests, Personal, Ownership Interest: AIQ Solutions; Financial Interests, Institutional, Principal Investigator: MVI, Concept, Pfizer; Financial Interests, Personal, Advisory Board: Janssen. All other authors have declared no conflicts of interest.

Background

Prostate cancer (PCa) is the second-most common non-cutaneous cancer in men with over 1.2 million men diagnosed worldwide annually. A large proportion of these men have indolent PCa and can safely defer treatment with active surveillance. Despite that, many patients are commonly treated with surgery (radical prostatectomy, RP) or radiation therapy, which are associated with a significant reduction in quality of life. In the past ten years, molecular signatures have been developed to assist clinicians in stratifying patients based on risk of aggressive PCa; while these have shown promise, there remains a significant opportunity for improving prognostic capacity.

Methods

A panel of fourteen prognostic genes was identified from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) database. In an Irish cohort of men diagnosed with PCa and treated with RP (PCRC, n=426), cross-validated logistic regression analysis identified a molecular risk score (MRS) with strong prognostic performance to predict aggressive PCa, i.e. adverse pathology (AP) at RP or biochemical recurrence (BCR). The MRS was combined with the Cancer of the Prostate Risk Assessment (CAPRA) score to create a Molecular + CAPRA risk score (MCRS).

Results

We identified a six-gene signature with improved prognostic value over clinical features. The MRS and MCRS were validated in an independent Swedish cohort of men diagnosed with PCa and treated by RP (UPCA, n=203). The AUC of the signature for AP was 0.83 (MCRS) and 0.75 (MRS) versus 0.69 for EAU risk categories and 0.76 for CAPRA. The C-index for BCR was 0.83 (MCRS) and 0.74 (MRS) versus 0.69 for EAU risk categories and 0.77 for CAPRA. Furthermore, the six-gene signature added statistically significant (p < 0.0001) prognostic value to CAPRA and EAU.

Conclusions

The six-gene prognostic signature has strong performance for both AP and BCR in an independent clinical validation study. It can assist clinicians and patients to determine whether active surveillance or active treatment is the most appropriate option based on their risk of aggressive disease and give confidence to men on their treatment choice.

Legal entity responsible for the study

OncoAssure Ltd.

Funding

OncoAssure Ltd.

Disclosure

A. Krzyzanowska, K.M. Sheehan, J. Fay, T. O'Grady, A. Bjartell: Financial Interests, Institutional, Funding: OncoAssure Ltd. S. Barron, T. Loughman, D.F. Higgins, A. Chan-Ju Wang, B. Fender, L.M. McGuire: Financial Interests, Personal, Full or part-time Employment: OncoAssure Ltd. D. O'Leary, W.M. Gallagher: Financial Interests, Personal, Full or part-time Employment: OncoAssure Ltd; Financial Interests, Personal, Stocks/Shares: OncoAssure Ltd. R.W.G. Watson: Financial Interests, Personal, Advisory Role: OncoAssure Ltd. All other authors have declared no conflicts of interest.

Background

PSMA-targeting radioligand therapy (PSMA-RLT) is a treatment option for metastatic castration-resistant prostate cancers (mCRPC). Patient’s selection is based on PSMA-PET positivity but the optimal lesion tracer uptake cut-offs are not defined. Also, intra-patient variability of PSMA expression and FDG uptake in mCRPC metastases may affect the efficacy of PSMA RLT. This study aimed to determine the prevalence of at least one PSMA-/FDG+ PET lesion in mCRPC patients and to determine its impact on decision to undergo PSMA compassionate RLT.

Methods

The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study (NCT04000776) is a prospective mCRPC PET-imaging trial. One hundred mCRPC patients with progression and showing at least three metastases by conventional imaging were accrued. ⁶⁸Ga-PSMA-617 and ¹⁸F-FDG PET/CT scans were performed within 10 days and analyzed quantitatively. Positivity of a lesion was defined as its SUV_peak being > 1.5 X SUV_mean of the liver.

Results

Median age, PSA and number of metastases per patient were 70 years [44 – 87], 50.1 ng/mL [17.9 – 210] and 4 [3 –99], respectively. At inclusion, 9.1, 19.2, 14.1 and 57.6% of patients had received 0, 1, 2 or >2 lines of systemic therapies (excluding castration) for prostate cancer, respectively. At least one PSMA-/FDG+ PET lesion was found in 45% of patients. In patients that received 0, 1, 2 or >2 lines of systemic therapies, the prevalence of at least one PSMA-/FDG+ PET lesion was 11.1, 26.3, 64.3 and 52.6 %, respectively (p=0.007, Cochran-Armitage test). Twenty-five patients underwent subsequent compassionate-access PSMA-RLT. Interestingly, 8 (32.0%) where found to have at least one PSMA-/FDG+ PET lesion by central quantitative blinded analysis.

Conclusions

A significant proportion of mCRPC patients show at least one PSMA-/FDG+ PET lesion and this proportion increases with lines of systemic therapies. Some patients with limited PSMA-/FDG+ disease were still offered compassionate PSMA-RLT. Further studies are needed to determine the significance of PSMA-/FDG+ PET lesions as a biomarker of PSMA-RLT candidacy.

Editorial acknowledgement

The authors wish to thank the Unité de recherche clinique et épidémiologique (URCE) of Centre de recherche du CHUS for their support in the writing of this abstract and specifically Ms Catherine Allard for the statistical assistance.

Legal entity responsible for the study

Université de Sherbrooke.

Funding

Oncopole program was funded by "Fonds de recherche du Québec-Santé (FRQS)", Merck, and the Cancer Research Society.

Disclosure

F. Pouliot: Non-Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Genzyme, Amgen, Astellas, Bayer, Janssen; Financial Interests, Institutional, Research Grant: Astellas. S. Probst: Non-Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Invited Speaker: Bayer, AbbVie, Astellas, Isologics, Lantheus, Point Biopharma. All other authors have declared no conflicts of interest.

Background

Quality of life (QoL) outcomes may differ among patients (pts) with prostate cancer (PCa) depending on disease setting, treatment received, and country/healthcare system.

Methods

In a large-scale, self-report digital survey, pts with non-metastatic (M–) and metastatic (M+) PCa in Germany, the UK and the US reported demographic and clinical factors, disease and treatment history, and QoL using validated measures (e.g., Functional Assessment of Cancer Therapy – Prostate [FACT-P]). Pts also rated their degree of positive vs. negative views of each type of PCa therapy not (yet) received and expected impact on QoL. Predictors of QoL were examined using analysis of variance, t-tests, and chi-square tests. Multivariate regression analysis examined the relative impact of one predictor while controlling for others. We assessed for between-group differences > 10, the previously defined cutoff for clinically meaningful FACT-P differences.

Results

Among 15 511 pts, 20% had M+ PCa and 37% had symptoms at diagnosis; 23% had diabetes, 27% cardiovascular disease and 9% kidney disease. Demographic factors were similar across countries. Pts had mostly negative views of therapy not yet received and expected negative impact on QoL. On univariate analysis, FACT-P scores were significantly better among pts with M– vs. M+ disease, pts with no comorbidities vs. ≥ 2 comorbidities and pts without vs. with severe comorbidity (Table). Age and PCa symptoms at diagnosis were not meaningfully associated with FACT-P scores. On multivariate analysis, M– vs. M+ disease and no comorbidities vs. ≥ 2 comorbidities showed meaningful differences in QoL. Table: 1401P

Average FACT-P scores across predictors

Conclusions

Self-reported QoL in pts with PCa did not vary substantially by country though treatment strategies differ. QoL was significantly affected by M+ status and comorbidity burden. QoL interventions should target these at-risk groups to reduce symptom burden, tolerance of treatment and fear of therapy.

Editorial acknowledgement

Under the guidance of the authors, Charlie Foster, PhD from Oxford PharmaGenesis (Oxford, UK) provided medical writing support for this abstract, with funding from Advanced Accelerator Applications, a Novartis Company.

Legal entity responsible for the study

Advanced Accelerator Applications, a Novartis Company.

Funding

Advanced Accelerator Applications, a Novartis Company.

Disclosure

J. O'Sullivan: Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications, a Novartis Company, Astellas, Bayer, Janssen, Sanofi; Financial Interests, Personal, Speaker’s Bureau: Advanced Accelerator Applications, a Novartis Company, Astellas, Bayer, Janssen, Sanofi; Financial Interests, Institutional, Research Grant: Bayer. B.D. Gonzalez: Financial Interests, Personal, Other, Consulting: SureMed Compliance, KemPharm; Financial Interests, Personal, Advisory Board: EllyHealth; Financial Interests, Personal, Invited Speaker: Society of Behavioral Medicine. R. Lehmann: Financial Interests, Personal, Officer, Founder and CEO: DontBePatient Intelligence; Financial Interests, Institutional, Research Grant, Founbding of the Prostate Cancer Patient Survey: Novartis/AAA. A. Poschenrieder, O. Mirante: Financial Interests, Personal, Stocks/Shares, Employee of Advanced Accelerator Applications, a Novartis Company: Novartis. A.K. Morgans: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, AAA, Bayer, Janssen, Exelixis, Myovant, Novartis, Pfizer, Sanofi; Financial Interests, Institutional, Research Grant: Astella, Bayer, Myovant, Sanofi. All other authors have declared no conflicts of interest.

Background

Subtype differentiation in prostate cancer (PCa) has been shown to be prognostic and predictive of androgen deprivation therapy (ADT) response in the postoperative setting. We sought to determine whether basal-luminal subtypes based on gene expression profiling of pretreatment biopsy samples would be predictive for the benefit of long- (LT; 24-28 months) vs short-term (ST; 4 months) ADT, hypothesizing that patients with basal tumors benefit more from longer term ADT.

Methods

Whole-transcriptome arrays of biopsy samples from patients enrolled in the NRG/RTOG 9202, 9413, and 9902 randomized phase III trials were analyzed. The prognostic and predictive ability of a 215 gene basal-luminal prostate subtyping classifier (PSC) was evaluated for biochemical failure (BF), distant metastasis (DM), metastasis-free survival (MFS), prostate cancer-specific mortality (PCSM), and overall survival (OS) with multivariable Cox models (MVA). Event rates were estimated by the cumulative incidence method and compared with Gray’s or logrank tests.

Results

265 samples were analyzed (40% PSC basal, 60% luminal). In MVA, the PSC basal subtype had a worse prognosis compared to PSC luminal for MFS (HR [95% CI] 1.8 [1.3-2.5], p<0.001), PCSM (HR 2.8 [1.5-5.0], p<0.001), and OS (HR 1.8 [1.3-2.6], p<0.001). PCSM rates at 10 years were 26% (95% CI 17-35%) for basal vs 11% (6-15%) for luminal subtypes. A significant interaction between PSC and ADT duration was observed for BF (p=0.02) and PCSM (p=0.007). Similar but non-significant trends were observed for DM, MFS, and OS. Basal subtypes significantly benefitted from LT- vs STADT (10-year PCSM 5% [95% CI 0-11%] vs 42% [29-56%], p<0.001), while luminal outcomes did not differ by ADT duration (p=0.72).

Conclusions

Gene expression analysis of pretreatment biopsy samples from three NRG phase III trials of high-risk PCa suggests that basal-luminal subtyping is predictive for the benefit of LT- vs STADT. Patients with basal tumors benefitted from longer term ADT while those with luminal did not, supporting the hypothesis that basal-luminal subtyping from biopsy samples can help personalize ADT duration in high-risk PCa.

Legal entity responsible for the study

NRG Oncology.

Funding

Veracyte, Inc., National Cancer Institute, Pfizer, Bristol Myers Squibb & Takeda Pharmaceutical.

Disclosure

V. Liu, J.A. Proudfoot, E. Davicioni, Y. Liu: Financial Interests, Personal, Full or part-time Employment: Veracyte. All other authors have declared no conflicts of interest.

Background

High TMB is a promising predictive biomarker for immune checkpoint blockade. Circulating tumor DNA (ctDNA) from plasma is a minimally invasive method that may ease TMB assessment. Prevalence and characteristics of metastatic prostate cancer (mPC) with high TMB is not well described.

Methods

We retrospectively reviewed all patients with mPC who underwent a liquid biopsy within the STING trial, NCT04932525 at Gustave Roussy. Genomic analyses were performed on plasma samples using the FoundationOne Liquid CDx (324 genes) next-generation sequencing assay. H-bTMB was defined with a cutoff >16mut/Mb (Gandara et al., 2018). We aimed to assess the proportion of h-bTMB and its association with clinical characteristics and molecular alterations. For patients with archived available primary tumor tissue, we compared TMB and genomic alterations in liquid and tissue (FoundationOne DX1).

Results

From November 2020 to February 2022, a liquid biopsy was performed in 281 patients with mPC. The median age was 70 years, 90% of patients had metastatic castration-resistant prostate cancer (mCRPC) and 73% had no visceral metastases. The median number of previous systemic therapies was 4 [IQR 2-5]. Overall, 275 patients were evaluable for bTMB. The median bTMB was 4mut/Mb (IQR 1-6), with bTMB>10mut/Mb in 32 (12%) patients and an h-bTMB (>16mut/Mb) in 15 (5%). Clinical characteristics were comparable between patients with and without h-bTMB. Among patients with h-bTMB, a deleterious alteration was found in BRCA 1/2 in six (40%) patients and in CDK12 in one (7%) patient. Furthermore, 7 (2.5%) patients had a microsatellite instability-high (MSI-h) ctDNA phenotype, including one with bTMB equal to 5mut/Mb. Eighty-five tumor tissue/ctDNA pairs were available for comparison. Among them, 4 patients had h-bTMB while only one displayed tissue TMB>10mut/Mb. Comprehensive genomic analyses will be presented at the meeting.

Conclusions

Only 5% patients had an h-bTMB (with a cutoff >16mut/Mb). H-bTMB was associated with DNA-repair alterations. Prospective studies assessing the relevance and the predictive impact of h-bTMB for immune checkpoint blockade efficacy are undergoing.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L. Lacroix: Financial Interests, Personal, Advisory Role: Adept Field solutions, AstraZeneca, Bayer, Boehringer, BMS, Lilly, Icomed, Illumina, Genomic Health, MedImmune, Novartis, Pfizer, QualWorld, Taiho Oncology, Roche, Thermofisher, VelaDX; Financial Interests, Personal, Other: Abbot, Amgen, Beckman Couletr, Guardant health, Myriad, Siemens, Healthineer. L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, AstraZeneca, BMS, EISAI, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Pfizer, BMS, Ipsen, AVEO, AstraZeneca, MSD; Non-Financial Interests, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU); Non-Financial Interests, Other, Member of the Kidney Cancer Research Summit scientific committee 2021: Kidney Can; Other, Scientific Committee: BMS France. E. Colomba: Financial Interests, Personal, Advisory Role: Ipsen, BMS, Sanofi, Tesaro, MSD, Eisai, Pfizer, GSK. R. Flippot: Financial Interests, Personal and Institutional, Other: Ipsen, Bayer, MSD, BMS, Astellas, Janssen. N. Naoun: Financial Interests, Personal, Other: Merck, Bayer. A. Patrikidou: Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Advisory Board: Basilea. S. Ponce: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Other: RSD Pharma. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion. Y. Loriot: Financial Interests, Personal, Advisory Board: Merck KGaA, Pfizer, Gilead, Seattle Genetics, Tahio; Financial Interests, Personal, Other, Lectures, Advisory Boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, Lectures, Advisory boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Invited Speaker: Janssen, Pfizer, janssen, MSD, Janssen, Exelexis, AstraZeneca, Pfizer, Merck KGaA, BMS, Astellas, Gilead, Incyte; Financial Interests, Invited Speaker: MSD, Astellas, Gilead/Immunomedics, Tahio; Financial Interests, Personal, Invited Speaker: Basilea; Non-Financial Interests, Member: ESMO, ASCO, AACR; Non-Financial Interests, Other, Scientific Committee: ARC. C. Baldini: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Expert Testimony: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Invited Speaker: iTeos, AZ, Janssen, Amgen, Bicycle Therapeutics, MSD, Seattle Genetics, Tahio; Non-Financial Interests, Member: ASCO, SIOG, SOFOG, AACR. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Invited Speaker: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. A. Bernard-Tessier: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Other, travel fees: Orion, Bayer; Financial Interests, Institutional, Advisory Board: Novartis; Non-Financial Interests, Principal Investigator: Amgen. All other authors have declared no conflicts of interest.

Background

JNJ-902 is a bispecific antibody that engages TMEFF2–expressing tumor cells and CD3 on T cells. TMEFF2 is a unique prostate cancer lineage antigen with expression independent of androgen receptor signaling and retained throughout disease progression. In preclinical studies, JNJ-902 showed exposure-dependent pro-inflammatory responses, potent T cell-mediated cytotoxicity, and robust antitumor activity.

Methods

This is a 2-part open-label, phase 1 study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary clinical activity of JNJ-902 monotherapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). In Part 1 (dose escalation), a modified continual reassessment method was used to guide decision making in dose escalation and selection of the part 2 expansion dose. Subcutaneous JNJ-902 was administered with first dose given with corticosteroid premedication. Part 2 (dose expansion) will further evaluate safety and preliminary clinical activity of JNJ-902 at the part 2 expansion dose.

Results

As of April 6, 2022, 73 pts in Part 1 received at least one dose of JNJ-902 in 9 cohorts of ascending doses. Most common treatment-related AEs were fatigue (45%), decreased appetite (44%), injection site erythema (37%), anemia (33%), back pain (25%), and arthralgia (22%). Dose-limiting toxicity was reported in 2 pts (all Grade 3; 1 pt, fall-required hospitalization; 1 pt, orthostatic hypotension and syncope). Cytokine release syndrome was reported in 4 pts and resolved within 2–3 days. No deaths related to JNJ-902 were reported. Anti-drug antibody development was uncommon. PSA decline of 50% (PSA50) was observed in 8 pts and confirmed PR in 5 pts. JNJ-902 has linear PK over range of doses studied.

Conclusions

JNJ-902 presented a tolerable safety profile at certain doses when PSA50 and RECIST responses were observed. JNJ-902 is being developed as a therapeutic option for mCRPC pts. Part 1 (dose escalation) is ongoing and Part 2 (dose expansion) of study will initiate once part 2 expansion dose is declared. Selection of part 2 expansion dosage is currently being adjusted and dose information will be presented.

Clinical trial identification

NCT04397276, EudraCT 2019-004885-16.

Editorial acknowledgement

Writing assistance was provided by Paul D. Cao, PhD, of Janssen Global Services, LLC.

Legal entity responsible for the study

Janssen R&D, LLC.

Funding

Janssen R&D.

Disclosure

E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Alkermes, Amunix, Anaveon, AstraZeneca, BMS, Janssen, MonTa, MSD, Nanobiotix, Nouscom, Novartis, Servier, TargImmune, T-knife, Chugai; Financial Interests, Personal, Invited Speaker: OncoDNA, PharmaMar, Roche/Genentech, BeiGene, MedSIR; Financial Interests, Personal, Other, Director, Clinical Research: START Madrid Group; Financial Interests, Personal, Full or part-time Employment, Director, Clinical Research: HM Hospitales Group; Financial Interests, Personal, Full or part-time Employment, Medical Oncologist. Clinical Investigator. Director, Clinical Research: START Madrid - CIOCC (Centro Integral Oncológico Clara Campal); Financial Interests, Personal, Ownership Interest: START, Oncoart Associated, International Cancer Consultants; Financial Interests, Institutional, Funding: Achilles; Financial Interests, Invited Speaker: EORTC IDMC; Non-Financial Interests, Invited Speaker, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) Foundation; Non-Financial Interests, Advisory Role: PsiOxus, Amcure; Non-Financial Interests, Member: ASCO, ESMO, SEOM, EORTC. J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Johnson & Johnson, MSD Oncology, Novartis (AAA), Pfizer, Roche, Sanofi; Financial Interests, Institutional, Invited Speaker: Janssen-Cilag International NV, Laboratoires Leurquin Mediolanum SAS, Lilly, S.A, MedImmune, Novartis Farmacéutica, S.A, Sanofi-Aventis, S.A. A. Avadhani: Non-Financial Interests, Institutional, Full or part-time Employment: Tempus Labs. D. Yao, V. Lin, S. Wu, P. Jaiprasart, J. Loffredo, M. Tamegnon, H. Xie: Non-Financial Interests, Institutional, Full or part-time Employment: Johnson and Johnson. All other authors have declared no conflicts of interest.

Background

TALAPRO-1 enrolled men with progressive mCRPC, measurable soft-tissue disease, and tumor DDRm involved directly or indirectly in homologous recombination repair (11-gene panel). Enrolled men had received 1–2 taxane-based chemotherapy regimens and progressed on ≥1 novel hormonal therapy. Confirmed objective response rate (primary endpoint; per RECIST 1.1; blinded independent central review [BICR]) was 29.8%. The molecular bases of prolonged clinical benefit with poly(ADP-ribose) polymerase inhibitors are incompletely understood, although limited evidence suggests that patients exhibiting large deletions in BRCA genes may experience extended benefit. Exploratory post hoc biomarker analyses assessed tumor genetics associated with prolonged antitumor benefit in TALAPRO-1.

Methods

Tumor alterations were assessed using FoundationOne®CDx. Zygosity of tumor alterations was predicted using somatic-germline-zygosity. Prolonged benefit was assessed as radiographic progression-free survival ([rPFS]; RECIST 1.1/PCWG3; BICR) time to event or censoring. Data cutoff was Sept 4, 2020 (primary completion date).

Results

Of 104 men in the efficacy population, 16 had rPFS of ≥12 months. Of their 16 tumors, 15 (94%) had BRCA2 alterations, including 10 large structural variants (9 copy number loss, 1 rearrangement) and 5 short variants (SV; 4 homozygous). In contrast, only 6/27 (22%) men with rPFS <2.0 months exhibited BRCA2 alterations (1 rearrangement, 1 non-defined, and 4 SV with 2 homozygous). Of 61 men with rPFS <12 months but ≥2 months, 36 (59%) had BRCA2 alterations (9 copy number loss, 1 rearrangement, 21 SV [11 homozygous], 2 multiple alterations [1 homozygous], and 3 not defined). Conversely, TP53 alterations were less common for men with rPFS ≥12 months vs <2 months (2/16 vs 14/27; P=0.02 Fisher’s exact test, 2-tails), potentially reflecting negative prognosis or a subgroup less sensitive to PARP inhibition.

Conclusions

Based on these retrospective, exploratory analyses of TALAPRO-1, men exhibiting prolonged benefit typically exhibited BRCA2 copy number loss or homozygous alterations, and lacked TP53 alterations.

Clinical trial identification

NCT03148795.

Editorial acknowledgement

This study was sponsored by Pfizer. Editorial support was provided by Maddie Higgins, MBiolSci, of CMC AFFINITY, McCann Health Medical Communications, and was funded by Pfizer.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

J.S. de Bono: Financial Interests, Personal, Advisory Board: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Genentech Roche, Genmab, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals; Financial Interests, Institutional, Advisory Board: Harpoon; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Bayer, Cellcentric, Daiichi, Genentech Roche, Genmab, GlaxoSmithKline, Harpoon, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Vertex Pharmaceuticals, Sanofi Aventis, Sierra Oncology, Taiho, Crescendo Biologics; Non-Financial Interests, Principal Investigator: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Genentech Roche, Genmab, GlaxoSmithKline, Harpoon, Janssen, Menarini Silicon Biosystems, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals; Non-Financial Interests, Institutional, Product Samples: Daiichi, Bayer, Pfizer, Merck Serono, AstraZeneca, Harpoon, Sierra Oncology, Genentech/Roche, Sanofi Aventis, GlaxoSmithKline. E. Castro Marcos: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Janssen, MSD, Bayer, Pfizer; Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, Clovis, Pfizer, Pfizer; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer; Financial Interests, Institutional, Research Grant: Janssen, Bayer; Financial Interests, Institutional, Invited Speaker: Janssen, Pfizer. D.A. Laird: Financial Interests, Institutional, Full or part-time Employment: Pfizer; Financial Interests, Institutional, Stocks/Shares: Pfizer. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion. T. Dorff: Financial Interests, Personal, Advisory Board: Seagen, AbbVie, AstraZeneca; Financial Interests, Institutional, Advisory Board: Exelixis; Financial Interests, Personal, Other, drafted educational content (unbranded): Astellas; Financial Interests, Institutional, Research Grant: Pfizer. S. Zhao: Financial Interests, Institutional, Other, Consulting Fees: AstraZeneca, EMD Serono, Exelixis, Janssen, Pfizer, Sanofi, Seattle Genetics; Financial Interests, Institutional, Research Grant: Pfizer. I.M. van Oort: Financial Interests, Institutional, Other, Consulting Fees: AAA Novartis, Astellas Pharma, Bayer, Ipsen, Janssen, MSD/AstraZeneca; Financial Interests, Institutional, Research Grant: Astellas Pharma, Bayer. F. Calabrò: Financial Interests, Institutional, Other, Consulting Fees: Merck Sharp & Dohme Oncology, Pfizer. S. Pignata: Financial Interests, Personal, Advisory Board: Roche, AZ, MSD, Clovis, GSK, PharmaMar; Financial Interests, Institutional, Funding: Roche, MSD, Pfizer, AZ. L. Geczi: Financial Interests, Institutional, Invited Speaker: Merck, BMS, Pfizer; Financial Interests, Institutional, Other, Travel, Accommodation Expenses: Merck, BMS, Pfizer. P. Barthelemy: Financial Interests, Institutional, Advisory Board: Amgen, Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Ipsen, Janssen-Cilag, Merck KGaA, MSD, MSD Oncology, and Pfizer; Financial Interests, Institutional, Other, travel expenses, including accommodation: Astellas Pharma, Bristol Myers Squibb, Ipsen, Janssen-Cilag, MSD, Pfizer. D. Kilari: Financial Interests, Personal, Other, Honoraria: Exelixis; Financial Interests, Personal, Advisory Board: Exelixis, Sanofi, Merck Sharp & Dohme, Myovant Sciences; Financial Interests, Personal, Speaker’s Bureau: Janssen, Exelixis, Astellas Pharma, Aveo Oncology; Financial Interests, Institutional, Research Grant: Astellas Pharma, Exelixis, Genentech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Exelixis, Janssen Recipient, Astellas Pharma, Aveo Oncology. J.F. Hopkins: Financial Interests, Institutional, Full or part-time Employment: Foundation Medicine Inc.; Financial Interests, Institutional, Stocks/Shares: Roche Holding AG. H. Chen, C.G. Healy: Financial Interests, Institutional, Ownership Interest: Pfizer; Financial Interests, Institutional, Full or part-time Employment: Pfizer. J. Chelliserry: Financial Interests, Institutional, Full or part-time Employment: Pfizer; Financial Interests, Institutional, Stocks/Shares: Pfizer. G.V. Scagliotti: Financial Interests, Personal and Institutional, Other, commercial interest, relationship(s), and Honoraria: AstraZeneca, Eli Lilly, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, and Takeda; Financial Interests, Institutional, Advisory Board: AstraZeneca, BeiGene, and Eli Lilly; Financial Interests, Institutional, Research Grant: Eli Lilly, MSD, and Tesaro; Financial Interests, Institutional, Other, Travel and Accommodation: Bayer. N. Mehra: Financial Interests, Personal, Advisory Board: Pfizer, Roche, MSD, AstraZeneca, Astellas, JNJ; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Funding: Astellas, Pfizer; Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Institutional, Invited Speaker: BMS, Janssen, BMS; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS; Non-Financial Interests, Leadership Role, Head of the Prostate Cancer Working group: Dutch Uro-Oncology Study Group; Non-Financial Interests, Principal Investigator, Co-PI: Prospective Bladder Cancer Infrastructure (Netherlands); Non-Financial Interests, Leadership Role: Castration-Resistant Prostate Cancer Registry. All other authors have declared no conflicts of interest.

Background

Metformin is associated with lower risks of developing prostate cancer (PCa), but its association with mortality in PCa is unclear. This study examined the associations between metformin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian, diabetic patients with PCa.

Methods

Diabetic adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 were retrospectively identified. Patients with <6 months of medical castration without subsequent bilateral orchidectomy, <6 months of concurrent metformin use and ADT, or missing baseline HbA1c were excluded. Metformin users had ≥6 months of concurrent metformin use and ADT, while non-users had no concurrent metformin use and ADT or never used metformin. Included patients were followed up until September 2021. The primary outcome was PCa-related mortality. The secondary outcome was all-cause mortality. Inverse probability treatment weighting was used to balance covariates.

Results

1971 patients (1284 metformin users and 687 non-users; mean age 76.2±7.8 years) were studied. Over a mean follow-up of 4.1±3.2 years, metformin users had significantly lower risks of PCa-related mortality (weighted hazard ratio (wHR) 0.49 [95% confidence interval 0.39-0.61], p<0.001) and all-cause mortality (wHR 0.53 [0.46-0.61], p<0.001), independent of diabetic control or status of chronic kidney disease. Such associations appeared stronger in patients without androgen receptor antagonist or chemotherapy use (Table). Table: 1416P

Weighted comparisons of outcomes by metformin usage with subgroups for androgen receptor antagonist or chemotherapy usage. Weighted hazard ratios (wHR) [95% confidence interval (CI)] were referenced against metformin non-users

Conclusions

Metformin use concurrent with ADT was associated with lower risks of mortality in Asian, diabetic patients with PCa. Its role as adjuvant therapy for PCa warrants further study.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E.C. Dee: Financial Interests, Institutional, Funding, NIH/NCI Support Grant P30 CA008748: National Institute of Health (NIH)/National Cancer Institute (NCI). All other authors have declared no conflicts of interest.

Background

In PROpel (NCT03732820), pts were enrolled irrespective of HRR gene mutation (HRRm) status. However, determination of HRRm and evaluation of radiographic progression-free survival by HRRm status were predefined endpoints. TT testing is considered the reference for assessment of HRRm but, given potential challenges in obtaining sufficient quantity of quality TT, ctDNA testing was also conducted.

Methods

Archival TT and blood samples were collected at baseline from >98% of randomised pts and analysed by the FoundationOne®CDx and FoundationOneLiquid®CDx molecular diagnostic tests, respectively. HRRm status (HRRm, non-HRRm or HRRm unknown) was assigned by individual test result and using an aggregate of the results from both tests. For aggregate results, pts were classified as HRRm if an HRRm was detected by either test; non-HRRm if no HRRm was detected by either test; or HRRm unknown if they did not have a valid HRRm test result.

Results

Of the 796 pts randomized, 782 had TT samples and 794 had blood samples available for testing. Of the pts with TT samples, 535 (68%) were successfully assessed for HRRm status by TT test, while 734 (92%) of pts with blood samples were successfully assessed by ctDNA test. Aggregate HRRm status was obtained for 778 (98%) pts (226 HRRm, 552 non-HRRm and 18 HRRm unknown). Using TT as a reference, positive-percent agreement was 80%, negative-percent agreement was 87%, overall-percent agreement was 85% and the positive and negative predictive values were 64% and 94%, respectively. In the HRRm by ctDNA subgroup 51 pts were non-HRRm by TT. The negative predictive value suggests that in the non-HRRm by ctDNA subgroup ∼174/186 (94%) pts would also be non-HRRm by TT test. Therefore, there were ∼12 potential false negative results by ctDNA test in the total non-HRRm aggregate population (2% of 552 pts).

Conclusions

There was good agreement between matched TT and ctDNA test results in PROpel. Using aggregate test results, it was possible to maximize the number of pts with known HRRm status while controlling the number of potential false negative results, thus facilitating robust analysis of HRRm status.

Clinical trial identification

NCT03732820.

Editorial acknowledgement

Medical writing support was provided by Laura Smart, MChem, at Mudskipper Business Ltd., funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

A.J. Armstrong: Financial Interests, Personal, Advisory Role: Janssen; Novartis; Myovant Sciences; Bayer; Exelixis; Dendreon; Merck; GoodRx; AstraZeneca; FORMA Therapeutics; Astellas Scientific and Medical Affairs Inc.; Pfizer; Bristol Myers Squibb; Exelixis; Financial Interests, Institutional, Funding: Gilead Sciences (Inst); Roche/Genentech (Inst); Bristol Myers Squibb (Inst); AstraZeneca (Inst); FORMA Therapeutics (Inst); Astellas Pharma (Inst); Constellation Pharmaceuticals (Inst); Dendreon (Inst); Pfizer (Inst); Amgen (Inst); Novartis (Inst); Jansse; Financial Interests, Institutional, Royalties: Circulating tumor cell novel capture technology (Inst); Financial Interests, Personal, Other, Travel/accommodation: Astellas Scientific and Medical Affairs Inc. F. Saad: Financial Interests, Personal, Other, Honoraria: AbbVie; Advanced Accelerator Applications; Astellas Pharma; AstraZeneca; Bayer; BMS; Janssen Oncology; Knight Therapeutics; Merck; Myovant Sciences; Novartis; Pfizer; Sanofi; Financial Interests, Personal, Advisory Role: AbbVie; Advanced Accelerator Applications; Astellas Pharma; AstraZeneca/MedImmune; Bayer; Janssen Oncology; Knight Therapeutics; Myovant Sciences; Novartis; Pfizer; Sanofi; Financial Interests, Institutional, Funding: Advanced Accelerator Applications (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Bayer (Inst); Bristol Myers Squibb (Inst); Janssen Oncology (Inst); Merck (Inst); Novartis (Inst); Pfizer (Inst); Sanofi (Inst). A. Thiery-Vuillemin: Financial Interests, Personal, Other, Honoraria: Pfizer; AstraZeneca; Sanofi; Janssen; Novartis; Ipsen; Roche/Genentech; Bristol Myers Squibb; MSD; Astellas Pharma; Financial Interests, Personal, Advisory Role: Pfizer; AstraZeneca; Sanofi; Janssen; Novartis; Ipsen; Roche; Bristol Myers Squibb; MSD; Astellas Pharma; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Personal, Other, Travel/accommodation: Roche; MSD; Janssen; Bristol Myers Squibb; AstraZeneca; Pfizer; Astellas Pharma; Ipsen. M. Oya: Financial Interests, Personal, Other, Honoraria: Bayer; Bristol Myers Squibb; Novartis; Ono Pharmaceutical; Pfizer; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Funding: Novartis; Pfizer. N.D. Shore: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, BMS, Dendreon, Ferring, Janssen, Merck, MDxHealth, Pfizer, Sanofi, Tolmar. N. Mehra: Financial Interests, Personal, Advisory Board: Pfizer, Roche, MSD, AstraZeneca, Astellas, JNJ; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Funding: Astellas, Pfizer; Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Institutional, Invited Speaker: BMS, Janssen, BMS; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS; Non-Financial Interests, Leadership Role, Head of the Prostate Cancer Working group: Dutch Uro-Oncology Study Group; Non-Financial Interests, Principal Investigator, Co-PI: Prospective Bladder Cancer Infrastructure (Netherlands); Non-Financial Interests, Leadership Role: Castration-resistant Prostate Cancer Registry. M. Ozguroglu: Financial Interests, Personal, Funding: Novartis, Roche, Janssen, Sanofi, Astellas; Financial Interests, Institutional, Funding: Novartis, Roche, Janssen, Sanofi, Astellas; Financial Interests, Personal, Other, Travel/Accommodation: BMS, Janssen, AstraZeneca. C. Gedye: Financial Interests, Institutional, Speaker’s Bureau: BMS, MSD, AZ, Iosen, Pfizer, AbbVie, Astellas, Amge; Financial Interests, Personal, Other, Travel support: BMS, MSD, Astellas; Financial Interests, Institutional, Other: MSD, BMS, Amgen. O. Sartor: Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications (AAA), Astellas, AstraZeneca, Bayer, Blue Earth Diagnostics, Inc., Bavarian Nordic, Bristol Myers Squibb, Clarity Pharmaceuticals, Clovis, Constellation, Dendreon, EMD Serono, Fusion, Isotopen Technologien Meunchen, Janss; Financial Interests, Personal, Funding: Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Constellation, Endocyte, Invitae, Janssen, Lantheus, Merck, Progenics, Tenebio. C.H. Poehlein: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. P. Qiu: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. Y. Liu, L. Riva, L. Harrington, L. Barker, P.M.D. Del Rosario, A. Barnicle: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. N. Clarke: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Janssen; Bayer; AstraZeneca.