Background

[¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617) delivers β-particle radiation to prostate-specific membrane antigen (PSMA) expressing cells and the surrounding microenvironment. In the phase III VISION study (NCT03511664), ¹⁷⁷Lu-PSMA-617 + protocol-permitted standard of care (SOC) prolonged radiographic progression-free survival (rPFS; HR, 0.40; 99.2% CI: 0.29, 0.57), overall survival (OS; 0.62; 95% CI: 0.52, 0.74) and time to first symptomatic skeletal event (SSE; 0.50; 95% CI: 0.40, 0.62) versus SOC (all p < 0.001).

Methods

VISION was an international, open-label study of ¹⁷⁷Lu-PSMA-617 in adults with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) previously treated with ≥ 1 androgen receptor pathway inhibitor and 1–2 taxane regimens. Patients were randomized 2:1 to ¹⁷⁷Lu-PSMA-617 (7.4 GBq every 6 weeks, ≤ 6 cycles) plus SOC or to SOC alone. rPFS and OS were alternate primary endpoints; time to SSE was a key secondary endpoint. Other secondary endpoints included safety and patient-reported HRQoL (Functional Assessment of Cancer Therapy – Prostate [FACT-P]) and pain (Brief Pain Inventory – Short Form [BPI-SF]). Pre-specified analyses included time to the first occurrence of HRQoL/pain worsening, disease progression or death. Ad hoc analyses included time to worsening only (non-inferential).

Results

HRQoL was assessed in the pre-specified rPFS analysis set comprising 581 of the 831 randomized patients (¹⁷⁷Lu-PSMA-617 arm, n = 385; control arm, n = 196). HRQoL and pain time-to-worsening analyses favoured the ¹⁷⁷Lu-PSMA-617 arm (Table), despite a higher incidence of grade ≥ 3 adverse events versus SOC alone. No new or unexpected safety concerns were noted, including changes in creatinine clearance. Table: 576MO

Hazard ratios for time to worsening in FACT-P and BPI-SF scores

Conclusions

¹⁷⁷Lu-PSMA-617 plus SOC was generally well tolerated and delayed time to HRQoL and pain worsening versus SOC alone in patients with advanced mCRPC.

Clinical trial identification

PSMA-617-01. 08 July 2019. EudraCT 2018-000459-41.

Editorial acknowledgement

Under the guidance of the authors, Dr Sarah Sabir from Oxford PharmaGenesis provided medical writing support for this abstract, with funding from Advanced Accelerator Applications, a Novartis Company.

Legal entity responsible for the study

Endocyte, Inc., a Novartis company.

Funding

Endocyte, Inc., a Novartis company.

Disclosure

K. Fizazi: Financial Interests, Institutional, Advisory Role: Janssen Oncology; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Institutional, Advisory Role: Astellas Pharma; Financial Interests, Institutional, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Orion Pharma GmbH; Financial Interests, Personal, Advisory Role: Curevac; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: ESSA; Financial Interests, Institutional, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Janssen; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: MSD; Financial Interests, Institutional, Other, Honoraria: Janssen; Financial Interests, Institutional, Other, Honoraria: Sanofi; Financial Interests, Institutional, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Bayer. K. Herrmann: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Bain Capital; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications, a Novartis company; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: BTG; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Institutional, Advisory Role: ITG; Financial Interests, Institutional, Advisory Role: ROTOP Pharmaka; Financial Interests, Personal, Advisory Role: Siemens Healthineers; Financial Interests, Personal, Advisory Role: GE Healthcare; Financial Interests, Personal, Leadership Role: SOFIE; Financial Interests, Personal, Ownership Interest: SOFIE. B.J. Krause: Financial Interests, Institutional, Funding: Advanced Accelerator Applications, a Novartis company; Financial Interests, Institutional, Funding: Endocyte, Inc., a Novartis company; Financial Interests, Institutional, Funding: Novartis. K. Rahbar: Financial Interests, Personal, Other, Honoraria: Advanced Accelerator Applications, a Novartis company; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: SIRTEX; Financial Interests, Personal, Advisory Role: ABX GmbH; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications, a Novartis company; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: ABX CRO. K.N. Chi: Financial Interests, Personal, Advisory Role: ESSA; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: POINT Biopharma; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Constellation Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Astellas Pharma; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: ESSA. M.J. Morris: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Endocyte, Inc., a Novartis Company; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications, a Novartis Company; Financial Interests, Personal, Advisory Role: ORIC Pharmaceuticals; Financial Interests, Personal, Advisory Role: Johnson & Johnson; Financial Interests, Personal, Advisory Role: Curium Pharma; Financial Interests, Personal, Advisory Role: Athenex; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Endocyte, Inc., a Novartis Company; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Fujifilm; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Endocyte, Inc., a Novartis Company; Financial Interests, Institutional, Funding: Progenics; Financial Interests, Institutional, Funding: Corcept Therapeutics; Financial Interests, Institutional, Funding: Roche/Genentech; Financial Interests, Institutional, Funding: Janssen. O. Sartor: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Dendreon; Financial Interests, Personal, Advisory Role: Constellation Pharmaceuticals; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications, a Novartis company; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Bavarian Nordic; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Progenics; Financial Interests, Personal, Advisory Role: Blue Earth Diagnostics; Financial Interests, Personal, Advisory Role: Myovant Sciences; Financial Interests, Personal, Advisory Role: Myriad Genetics; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Clarity Pharmaceuticals; Financial Interests, Personal, Advisory Role: Fusion Pharmaceuticals; Financial Interests, Personal, Advisory Role: Isotopen Technologien; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Noxopharm; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Noria Therapeutics; Financial Interests, Personal, Advisory Role: Point Biopharma; Financial Interests, Personal, Advisory Role: TeneoBio; Financial Interests, Personal, Advisory Role: Telix Pharmaceuticals; Financial Interests, Personal, Advisory Role: Theragnostics; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Bayer; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Johnson & Johnson; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Sanofi; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Progenics; Financial Interests, Personal, Expert Testimony: Sanofi; Financial Interests, Personal, Ownership Interest: Lilly; Financial Interests, Personal, Ownership Interest: GlaxoSmithKline; Financial Interests, Personal, Ownership Interest: Abbvie; Financial Interests, Personal, Ownership Interest: Cardinal Health; Financial Interests, Personal, Ownership Interest: United Health Group; Financial Interests, Personal, Ownership Interest: PSMA Therapeutics; Financial Interests, Personal, Ownership Interest: Clarity Pharmaceuticals; Financial Interests, Personal, Ownership Interest: Noria Therapeutics; Financial Interests, Personal, Ownership Interest: Clovis Oncology; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Endocyte Inc., a Novartis company; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: InVitae; Financial Interests, Institutional, Funding: Constellation Pharmaceuticals; Financial Interests, Institutional, Funding: Advanced Accelerator Applications, a Novartis company; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Dendreon; Financial Interests, Personal, Funding: SOTIO; Financial Interests, Personal, Funding: Janssen; Financial Interests, Personal, Funding: Progenics; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Endocyte Inc., a Novartis company; Financial Interests, Personal, Advisory Role: Taiho; Financial Interests, Institutional, Funding: Arvinas. S.T. Tagawa: Financial Interests, Personal, Advisory Role: Medivation; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Dendreon; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Endocyte Inc., a Novartis company; Financial Interests, Personal, Advisory Role: Immunomedics; Financial Interests, Personal, Advisory Role: Karyopharm Therapeutics; Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Personal, Advisory Role: Tolmar; Financial Interests, Personal, Advisory Role: QED Therapeutics; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: POINT Biopharma; Financial Interests, Personal, Advisory Role: Blue Earth Diagnostics; Financial Interests, Personal, Advisory Role: AIkido Pharma; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Sanofi; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Immunomedics; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Amgen; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Astellas Pharma; Financial Interests, Institutional, Funding: Progenics; Financial Interests, Institutional, Funding: Millennium; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Dendreon; Financial Interests, Institutional, Funding: Rexahn Pharmaceuticals; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: Newlink Genetics; Financial Interests, Institutional, Funding: Inovio Pharmaceuticals; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Immunomedics; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: AVEO; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Stem CentRx; Financial Interests, Institutional, Funding: Karyopharm Therapeutics; Financial Interests, Institutional, Funding: Abbvie; Financial Interests, Institutional, Funding: Medivation; Financial Interests, Institutional, Funding: Endocyte Inc., a Novartis company; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Institutional, Funding: Clovis Oncology; Non-Financial Interests, Personal, Other: Telix Pharmaceuticals; Non-Financial Interests, Personal, Other: ATLAB Pharma; Non-Financial Interests, Personal, Other: Phosplatin Therapeutics; Financial Interests, Institutional, Funding: POINT Biopharma; Financial Interests, Institutional, Funding: Gilead Sciences. A.T. Kendi: Other, Personal, Principal Investigator, PI at Mayo Clinic Rochester for VISION trial: Endocyte, Inc., a Novartis Company. N.J. Vogelzang: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Speaker’s Bureau: Sanofi adventis; Financial Interests, Personal, Advisory Board: Sanofi adventis; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Speaker’s Bureau: Dendreon; Financial Interests, Personal, Advisory Board: Dendreon. J. Calais: Financial Interests, Personal, Other, Honoraria: Advanced Accelerator Applications, a Novartis company; Financial Interests, Personal, Advisory Role: Blue Earth Diagnostics; Financial Interests, Personal, Advisory Role: Curium Pharma; Financial Interests, Personal, Advisory Role: GE Healthcare; Financial Interests, Personal, Invited Speaker: IBA RadioPharma; Financial Interests, Personal, Advisory Role: Janssen Pharmaceuticals; Financial Interests, Personal, Advisory Role: POINT biopharma; Financial Interests, Personal, Advisory Role: Progenics / Lantheus; Financial Interests, Personal, Principal Investigator: Progenics / Lantheus; Financial Interests, Personal, Other, Honoraria: Radiomedix; Financial Interests, Personal, Invited Speaker: Telix Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Progenics / Lantheus. J. Nagarajah: Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Personal, Advisory Role: Curium. X.X. Wei: Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Funding: BMS. V.S. KOSHKIN: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Clovis; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: Seattle Genetics / Astellas; Financial Interests, Personal, Advisory Role: Dendreon; Financial Interests, Institutional, Funding: Endocyte Inc., a Novartis company; Financial Interests, Institutional, Funding: Nektar; Financial Interests, Institutional, Funding: Clovis; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Taiho; Other, Personal, Other: Prostate Cancer Foundation. J. Beauregard: Non-Financial Interests, Personal and Institutional, Principal Investigator: Advanced Accelerator Applications, a Novartis company; Non-Financial Interests, Personal and Institutional, Principal Investigator: Ipsen; Non-Financial Interests, Personal, Advisory Role: Ipsen. M. DeSilvio: Financial Interests, Personal, Full or part-time Employment: Novartis Pharmaceuticals; Financial Interests, Personal, Ownership Interest: Novartis Pharmaceuticals. R.A. Messmann: Financial Interests, Personal, Full or part-time Employment: Novartis Pharmaceuticals; Financial Interests, Personal, Ownership Interest: Novartis Pharmaceuticals. J. de Bono: Financial Interests, Personal, Full or part-time Employment: Institute of Cancer Research; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Sierra Oncology; Financial Interests, Personal, Advisory Role: Menarini Silicon Biosystems; Financial Interests, Personal, Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Janssen Oncology; Financial Interests, Personal, Advisory Role: Genmab; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Orion Pharma GmbH; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: BioXCel therapeutics; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: CellCentric; Financial Interests, Personal, Advisory Role: Harpoon; Financial Interests, Personal, Advisory Role: Qiagen; Financial Interests, Personal, Advisory Role: Terumo; Financial Interests, Personal, Advisory Role: Sanofi Aventis GmbH; Financial Interests, Personal, Advisory Role: Vertex; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Astellas Pharma; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: GlaxoSmithKline; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Orion Pharma GmbH; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Sanofi; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Genmab; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Taiho Pharmaceutical; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Qiagen; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Vertex; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Amgen; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Bayer; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Bioexcel Therapeutics; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Boehringer Ingelheim; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Cellcentric; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Daiichi Sankyo; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Eisai; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Genentech/Roche; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Harpoon; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Janssen; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Menarini Silicon Biosystems; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Merck Serono; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Pfizer; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Qiagen; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Sierra Oncology; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Terumo; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Genentech/Roche; Financial Interests, Personal, Other, Honoraria: Janssen Oncology; Financial Interests, Personal, Other, Honoraria: Menarini Silicon Biosystems; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: Sierra Oncology; Financial Interests, Personal, Other, Honoraria: BioExcel; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: CellCentric; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Genmab; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: Harpoon; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria: Orion; Financial Interests, Personal, Other, Honoraria: Qiagen; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Terumo; Financial Interests, Personal, Other, Honoraria: Vertex; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Astex Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Medivation; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Sanofi; Financial Interests, Personal, Funding: Taiho Pharmaceutical; Financial Interests, Personal, Funding: Daiichi Sankyo; Financial Interests, Personal, Funding: Merck Serono; Financial Interests, Personal, Funding: Astex Pharmaceuticals; Financial Interests, Personal, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Funding: Orion Pharma GmbH; Financial Interests, Personal, Funding: GlaxoSmithKline; Financial Interests, Personal, Funding: CellCentric; Financial Interests, Personal, Funding: Sierra Oncology; Financial Interests, Personal, Funding: Bayer; Financial Interests, Personal, Funding: Amgen; Financial Interests, Personal, Funding: Astellas Pharma; Financial Interests, Personal, Funding: Genmab; Financial Interests, Personal, Funding: Harpoon; Financial Interests, Personal, Funding: Janssen; Financial Interests, Personal, Funding: Menarini Silicon Biosystems; Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Funding: Vertex; Financial Interests, Personal, Funding: Genentech/Roche; Financial Interests, Personal, Funding: Sanofi Aventis GmbH. All other authors have declared no conflicts of interest.

Background

Treatment options for patients (pts) with mCRPC have evolved with introduction of NHAs. We hypothesize that maintenance treatment with Darolutamide (Daro) for pts with disease stabilization under chemotherapy after pretreatment with another NHA can delay disease progression.

Methods

SAKK 08/16 is a randomized placebo-controlled double-blind phase 2 study. Pts with mCRPC and prior NHA therapy and non-progressive disease on taxane (docetaxel >=300mg/m² or cabazitaxel >=80mg/m²) were eligible. Pts received Daro 600mg bd or placebo bd starting 2-8 weeks (wks) after end of taxane. Primary endpoint: radiographic progression-free survival at 12 wks (rPFS12). Secondary endpoints: rPFS, event-free survival (EFS), overall survival (OS), PSA 50% response (PSA50 RR), adverse events (AE). 88 pts were needed to show superiority of Daro for rPFS12 (type I error 15%, power 80%).

Results

92 pts were accrued between 3/17 – 11/20. Median follow-up is 18 months (mo). Median age was 72 years (55-87). Prior taxane was docetaxel in 93% and cabazitaxel in 7%. Prior NHA was Abiraterone in 60%, Enzalutamide in 31% and both in 9%. rPFS12 was significantly improved with Daro 64.7% vs placebo 52.2% (p=0.127, below significance level of 0.15). Median rPFS on Daro was 5.5 mo vs 4.5 mo on placebo (HR 0.54; 95% CI 0.32-0.91; p=0.017) and median EFS 5.4 mo vs 2.9 mo (HR 0.46; 95% CI 0.29-0.73; p=0.001). PSA50 RR was 22% on Daro vs 4% on placebo (p=0.014). Median OS on Daro was 24 mo vs 21.3 mo on placebo (HR 0.62; 95% CI 0.3-1.26; p= 0.181). Treatment related AEs were mild and similar in both arms (Daro vs placebo): G1 26% vs 22%, G2 13% vs 15%, G3 2% vs 2%. Fatigue G1/2 was less common in Daro arm (11% vs 20%).

Conclusions

This proof of concept study met its primary endpoint and shows that switch maintenance with Daro after prior taxane and at least one NHA results in a statistically significant but clinically modest prolongation of rPFS and EFS with good tolerability. Median OS with Daro maintenance is promising and numerically superior to the control arm.

Clinical trial identification

NCT02933801.

Legal entity responsible for the study

SAKK Swiss Working Group for Clinical Cancer Research.

Funding

Bayer and SERI (Swiss State Secretariat for Education, Research and Innovation).

Disclosure

R. Cathomas: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Institutional, Advisory Board: Ipsen; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: Debiopharm; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Astellas. G. Procopio: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Novartis. O. Caffo: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: AAA. A.G. Omlin: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: Molecular Partners; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Research Grant: TEVA; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Speaker’s Bureau: Astellas; Financial Interests, Institutional, Speaker’s Bureau: Bayer; Financial Interests, Institutional, Speaker’s Bureau: Janssen. S. Gillessen: Financial Interests, Institutional, Other: Janssen; Financial Interests, Institutional, Other: RSI; Financial Interests, Institutional, Advisory Role: AAA; Financial Interests, Institutional, Advisory Role: Amgen; Financial Interests, Institutional, Advisory Role: Aranda; Financial Interests, Institutional, Advisory Role: Astellas; Financial Interests, Institutional, Advisory Role: Bayer; Financial Interests, Institutional, Advisory Role: BMS; Financial Interests, Institutional, Advisory Role: Janssen; Financial Interests, Institutional, Advisory Role: Menarini Silicon Biosystems; Financial Interests, Institutional, Advisory Role: MSD; Financial Interests, Institutional, Advisory Role: MSD; Financial Interests, Institutional, Advisory Role: Orion; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Advisory Role: Sanofi; Financial Interests, Institutional, Advisory Role: Telixpharma; Financial Interests, Institutional, Advisory Role: Toledo Pharmaceuticals; Financial Interests, Institutional, Other: Proteomedix. All other authors have declared no conflicts of interest.

Background

Sabizabulin is a novel oral agent that targets microtubules to disrupt transport of the AR. A phase Ib/II clinical study was conducted to assess safety, maximum tolerated dose and efficacy in men with mCRPC that progressed on an ARTA.

Methods

A phase Ib/II study was conducted in men with mCRPC who have failed an ARTA. The phase Ib portion (n=39) utilized a 3+3 design with escalating oral dosing of 4.5 mg to 81 mg for 7 days on /14 days off drug per 21-day cycle, then was expanded to continuous daily dosing. The phase II portion (n=41) evaluated the recommended phase II dose (63 mg PO daily). A PK study evaluating the phase II and phase III trial dosage forms was also conducted.

Results

Sabizabulin was well tolerated with the most common adverse events (>10% frequency) in patients that received 63 mg dose (n=54) including diarrhea, fatigue, ALT and AST increases which were mostly Grade 1 and 2. In the phase Ib portion, in men who were treated with 63 mg (n=14), the median duration on study was 10.8 m (2.3-24.7m). In the men with measurable disease (n=9), the ORR was 44% (n=4). For men ≥ 60mg dose (n=19), the estimated rPFS is 12.4 m (3 men still on study). The phase II is ongoing with evidence of PSA responses and objective responses. When combining phase Ib/II trials, in patients with measurable disease at baseline (n=29), the ORR (5PR +1CR observed) was 20.7%. In patients that received ≥ 63 mg (excluding baseline superscans) (n=55), the median rPFS is estimated to be 7.4 months with 10 men on study (Feb 2021). In the PK study, the phase III dose form had better oral bioavailability than the phase II dose form, thus the phase III recommended dose is 32mg PO qD.

Conclusions

In the phase Ib/II clinical trial, oral 63mg daily dosing has a favorable safety profile and chronic dosing is feasible. Efficacy was observed with PSA declines and long term durable responses. The phase III VERACITY study evaluating sabizabulin in chemotherapy naïve men with mCRPC who have failed an AR targeting agent is ongoing. Sabazibulin appears to be in a similar class of other FDA approved targeted cytostatic drugs that have shown to significantly prolong progression and survival.

Clinical trial identification

NCT03752099.

Legal entity responsible for the study

Veru Inc.

Funding

Veru Inc.

Disclosure

M.C. Markowski: Financial Interests, Institutional, Principal Investigator: Veru Inc. M. Eisenberger: Financial Interests, Personal, Member of the Board of Directors: Veru Inc. C.M. Pieczonka: Financial Interests, Institutional, Principal Investigator: Veru Inc. R.H. Getzenberg: Financial Interests, Personal, Full or part-time Employment: Veru Inc. D. Rodriguez: Financial Interests, Personal, Full or part-time Employment: Veru Inc. K.G. Barnette: Financial Interests, Personal, Leadership Role: Veru Inc. M.S. Steiner: Financial Interests, Personal, Leadership Role: Veru Inc. D.R. Saltzstein: Financial Interests, Institutional, Principal Investigator: Veru Inc. E.S. Antonarakis: Financial Interests, Institutional, Member: Veru Inc. R. Tutrone: Financial Interests, Institutional, Principal Investigator: Veru Inc.

Background

CheckMate 9KD is a phase II, multi-cohort trial of NIVO (anti–PD-1) combined with rucaparib, docetaxel, or enzalutamide for mCRPC. We report results for cohort A2, assessing NIVO + rucaparib for CT-naïve mCRPC.

Methods

In cohort A2, unselected patients (pts) with CT-naïve mCRPC, ongoing ADT, prior abiraterone and/or enzalutamide for mCRPC, and no prior PARP inhibitors received NIVO 480 mg Q4W + rucaparib 600 mg BID until disease progression/unacceptable toxicity (NIVO dosing ≤ 2 y). Coprimary endpoints were objective response rate (ORR) per PCWG3 criteria and prostate-specific antigen response rate (PSA-RR) in all treated pts and pts with homologous recombination deficiency positive (HRD+) tumors; HRD status was determined before enrollment. Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety.

Results

Of 71 treated pts, median age 73 y (range, 51–87 y), 23.9% had visceral metastases and 54.9% had measurable disease. Median treatment duration was 4.6 mo for NIVO and 5.5 mo for rucaparib; median follow-up was 17.5 mo. The table summarizes efficacy results, and shows better outcomes for HRD+ vs HRD–/not evaluable tumors. Any-grade treatment-related AEs (TRAEs) occurred in 90.1% of pts, most commonly nausea (40.8%) and anemia (32.4%). Grade ≥ 3 TRAEs occurred in 50.7% of pts, most commonly anemia (14.1%) and increased ALT (12.7%). TRAEs led to discontinuation in 23.9% of pts. No treatment-related deaths were reported. Table: 579MO

Conclusions

NIVO + rucaparib is active in pts with HRD+ CT-naïve mCRPC. Longer follow-up is needed to better characterize clinical benefits of adding NIVO to rucaparib for this population. Clinical activity in pts with HRD– tumors was limited. The safety profile of NIVO + rucaparib was as expected based on the individual components, with no new safety signals. Ongoing biomarker analyses will assess the impact of specific HRD mutations on treatment efficacy.

Clinical trial identification

NCT03338790.

Editorial acknowledgement

Writing and editorial assistance was provided by Richard Daniel, PhD, of Parexel, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

D.P. Petrylak: Financial Interests, Personal, Other, Consultant Fees: Ada Cap (Advanced Accelerator Applications) Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Incyte, Janssen, Mirati, Monopteros, Pfizer, Pharmacyclics, Roche, Se; Financial Interests, Personal, Stocks/Shares: Bellicum (Sold 7/2020), Tyme (sold 10/2019); Financial Interests, Institutional, Invited Speaker: Ada Cap (Advanced Accelerator Applications), Agensys Inc, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Eisai, Eli Lilly, Endocyte, Genentech, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer. J.L. Perez-Gracia: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Principal Investigator, Local PI: Amgen; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Personal, Funding: Ipsen; Non-Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Seattle Genetics; Other, Personal, Other, Travel Support: Roche. L. Lacombe: Financial Interests, Institutional, Invited Speaker, Clinical studies: Astra-Zeneca; Financial Interests, Institutional, Invited Speaker, Clinical studies: BMS; Financial Interests, Institutional, Invited Speaker, Clinical studies: Merck; Financial Interests, Institutional, Invited Speaker, Clinical studies: Pfizer; Financial Interests, Institutional, Invited Speaker, Clinical studies: Telix; Financial Interests, Institutional, Invited Speaker, Clinical studies: Janssen; Financial Interests, Institutional, Invited Speaker, Clinical studies: Astellas; Financial Interests, Institutional, Invited Speaker, null: Myovant; Financial Interests, Institutional, Invited Speaker, Clinical studies: Hoffmann- La Roche; Financial Interests, Institutional, Invited Speaker, Clinical studies: Medimmune; Financial Interests, Institutional, Invited Speaker, Clinical studies: Bayer; Financial Interests, Institutional, Invited Speaker, Clinical studies: Sanofi. D.A. Bastos: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: AztraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Janssen. H. Mahammedi: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi; Non-Financial Interests, Personal, Principal Investigator: BMS; Non-Financial Interests, Personal, Principal Investigator: Janssen; Non-Financial Interests, Personal, Principal Investigator: MSD; Non-Financial Interests, Personal, Principal Investigator: Pfizer; Non-Financial Interests, Personal, Principal Investigator: Roche; Non-Financial Interests, Personal, Principal Investigator: Sanofi. E.M. Kwan: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Writing Engagements: Research Review; Financial Interests, Institutional, Principal Investigator, Local PI ARCHES study: Astellas Pharma; Financial Interests, Institutional, Principal Investigator, Local PI PROFOUND: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Local PI CheckMae 9KD: BMS; Financial Interests, Institutional, Invited Speaker, Coordinating PI ICE-PAC: Merck KGaA; Financial Interests, Institutional, Invited Speaker, Local PI TALAPRO: Pfizer; Non-Financial Interests, Personal, Principal Investigator, ARCHES: Astellas Pharma; Non-Financial Interests, Personal, Principal Investigator, PROFOUND: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, CheckMate 9KD: BMS; Non-Financial Interests, Personal, Principal Investigator, ICE-PAC: Merck KGaA; Non-Financial Interests, Personal, Principal Investigator, TALAPRO: Pfizer. S. Zschäbitz: Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Other, Travel Grant: Celgene; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Advisory Board: EUSA; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Principal Investigator, Local PI: Astellas; Financial Interests, Principal Investigator, Coordinating PI: BMS; Financial Interests, Principal Investigator, Local PI: Calithera Biosciences; Financial Interests, Principal Investigator, Local PI: Clovis Oncology; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Principal Investigator, Local PI: Exelixis; Financial Interests, Principal Investigator, Local PI: Pfizer; Financial Interests, Principal Investigator, Local PI: Roche; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: DGHA. A.J. Armstrong: Financial Interests, Personal, Other, Consultant: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Dendreon; Financial Interests, Personal, Invited Speaker: Forma; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Principal Investigator, Local PI: Amgen; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Astellas; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Bayer; Financial Interests, Institutional, Principal Investigator, Local PI: Beigene; Financial Interests, Institutional, Principal Investigator, Coordinating PI: BMS; Financial Interests, Institutional, Member, Steering Committee Member: Dendreon; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Janssen; Financial Interests, Institutional, Principal Investigator, Local PI: Merck; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Pfizer. R.K. Pachynski: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Dendreon; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Invited Speaker: Genentech/Roche; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Jounce; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Member, Steering Committee Member: BMS; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Pharmacylics; Financial Interests, Personal, Invited Speaker: Sanofi; Non-Financial Interests, Principal Investigator: BMS; Non-Financial Interests, Principal Investigator: ESSA; Non-Financial Interests, Principal Investigator: Janssen; Non-Financial Interests, Principal Investigator: Merck; Non-Financial Interests, Principal Investigator: Pfizer/EMD Serono. J.C. Goh: Financial Interests, Personal, Advisory Board, Prior member of BMS RCC Advisory Board: BMS; Non-Financial Interests, Personal, Principal Investigator, Local PI for CheckMate 9KD trial, CheckMate- 7DX CheckMate 9ER: BMS. M. Burotto: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche. G. Gravis: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Alliance Merck-Pfizer; Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Principal Investigator, Coordinating PI: BMS; Financial Interests, Institutional, Other, Travel accommodations expenses: BMS; Financial Interests, Institutional, Other, Travel accommodations expenses: Janssen; Financial Interests, Institutional, Other, Travel accommodations expenses: Sanofi. S.L. McCune: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Institutional, Principal Investigator, Local PI for clinical trials sponsored by BMS: BMS; Financial Interests, Institutional, Principal Investigator, Local PI on Merck studies: Merck; Financial Interests, Institutional, Principal Investigator, Local PI on ompany sponsored clinical trials: Roche Genentech. J.C. Vázquez Limón: Financial Interests, Institutional, Full or part-time Employment, Attending physician and chief of oncology service: Hospital Civil de Guadalajara \"Fray Antonio Alcalde; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: Europharma; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: Janssen; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: MSD; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: Novartis. F. Saad: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Myovant; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Institutional, Principal Investigator, Local PI: Amgen; Financial Interests, Institutional, Principal Investigator, Local PI: Astellas; Financial Interests, Institutional, Principal Investigator, Local PI: Bayer; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Local PI: Janssen; Financial Interests, Institutional, Principal Investigator, Local PI: Novartis; Financial Interests, Institutional, Principal Investigator, Local PI: Pfizer; Financial Interests, Institutional, Principal Investigator, Local PI: Sanofi. N.P. Amin: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. J. Li: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. K. Unsal-Kacmaz: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. K. Fizazi: Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: Curevac; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Research Grant, Trial chair: Bayer; Financial Interests, Institutional, Research Grant, Trial chair: BMS; Financial Interests, Institutional, Research Grant, Trial chair: Janssen; Financial Interests, Institutional, Research Grant, Trial chair: MSD; Financial Interests, Institutional, Research Grant, Trial chair: Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer. All other authors have declared no conflicts of interest.