Abstract 648TiP
Background
[177Lu]Lu-PSMA-617 (177Lu-PSMA-617) is a high-affinity prostate-specific membrane antigen (PSMA)-targeted radioligand therapy that delivers β-particle radiation to PSMA-expressing cells and their surrounding microenvironment. In the phase III VISION trial, 177Lu-PSMA-617 significantly prolonged radiographic progression-free survival (rPFS) and overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with ≥ 1 androgen receptor pathway inhibitor (ARPI) and 1–2 taxanes. PSMAfore is investigating the effect on rPFS in taxane-naïve patients with mCRPC treated with either 177Lu-PSMA-617 or a change in ARPI.
Trial design
PSMAfore (NCT04689828) is a multicentre, open-label, randomized phase III trial in adults with progressive mCRPC and confirmed PSMA expression by [68Ga]Ga-PSMA-11 PET/CT. Eligible patients are taxane-naïve in the metastatic setting and have: received one prior ARPI and are candidates for a change in ARPI; an ECOG performance status of 0 or 1; a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L); and recovered to grade ≤ 2 from toxicities related to prior therapies. Approximately 450 patients will be randomized 1:1 to receive 177Lu-PSMA-617 (7.4 GBq i.v. every 6 weeks for 6 cycles) or a change in ARPI to either abiraterone or enzalutamide. Best supportive care is allowed in both arms. Stratification factors are prior ARPI use in castration-resistant vs hormone-sensitive prostate cancer settings and pain symptomatology (score 0–3 vs 4–10 on the worst pain intensity item of the Brief Pain Inventory – Short Form). The primary endpoint is rPFS according to PCWG3-modified RECIST v1.1 criteria. Participants with blinded independent centrally confirmed radiographic progression in the ARPI arm can crossover to the 177Lu-PSMA-617 arm. The planned sample size provides 95% power to detect a hazard ratio of 0.56 for rPFS after 156 events with an overall one-sided significance level of 0.025. The key secondary endpoint is overall survival; other secondary endpoints include safety and tolerability of 177Lu-PSMA-617 and health-related quality of life.
Clinical trial identification
CAAA617B12302, EUDRACT 2020-003969-19.
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
Novartis Pharmaceuticals.
Funding
Novartis Pharmaceuticals.
Disclosure
M.J. Morris: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Endocyte; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications; 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, Accommodations, Expenses: Endocyte; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Fujifilm; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Endocyte; 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; 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, Accommodations, Expenses: Bayer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Johnson & Johnson; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sanofi; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Progenics; Financial Interests, Personal, Expert Testimony: Sanofi; Financial Interests, Personal, Stocks/Shares: Lilly; Financial Interests, Personal, Stocks/Shares: GlaxoSmithKline; Financial Interests, Personal, Stocks/Shares: Abbvie; Financial Interests, Personal, Stocks/Shares: Cardinal Health; Financial Interests, Personal, Stocks/Shares: United Health Group; Financial Interests, Personal, Stocks/Shares: PSMA Therapeutics; Financial Interests, Personal, Stocks/Shares: Clarity Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Noria Therapeutics; Financial Interests, Personal, Stocks/Shares: Clovis Oncology; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Endocyte; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: InVitae; Financial Interests, Institutional, Funding: Constellation Pharmaceuticals; Financial Interests, Institutional, Funding: Advanced Accelerator Applications; 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. 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. J.S. de Bono: Financial Interests, Personal, Other, Employee: 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, Institutional, Royalties: Abiraterone Rewards to Inventors; Financial Interests, Institutional, Royalties: PARP inhibitors and DNA repair defects; Financial Interests, Institutional, Royalties: Targeting of IL23 in prostate cancer; Financial Interests, Institutional, Royalties: CHK1 inhibitor; 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. N.D. Shore: Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Personal, Other, Honoraria: Abbvie; Financial Interests, Personal, Research Grant: Abbvie; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Other, Honoraria: Astellas; Financial Interests, Personal, Research Grant: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Boston Scientific; Financial Interests, Personal, Other, Honoraria: Boston Scientific; Financial Interests, Personal, Research Grant: Boston Scientific; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Other, Honoraria: Clovis Oncology; Financial Interests, Personal, Research Grant: Clovis Oncology; Financial Interests, Personal, Advisory Role: Dendreon; Financial Interests, Personal, Other, Honoraria: Dendreon; Financial Interests, Personal, Research Grant: Dendreon; Financial Interests, Personal, Advisory Role: Exact Imaging; Financial Interests, Personal, Other, Honoraria: Exact Imaging; Financial Interests, Personal, Research Grant: Exact Imaging; Financial Interests, Personal, Advisory Role: FerGene; Financial Interests, Personal, Other, Honoraria: FerGene; Financial Interests, Personal, Research Grant: FerGene; Financial Interests, Personal, Advisory Role: Foundation Medicine; Financial Interests, Personal, Other, Honoraria: Foundation Medicine; Financial Interests, Personal, Research Grant: Foundation Medicine; Financial Interests, Personal, Advisory Role: GC Oncology; Financial Interests, Personal, Other, Honoraria: GC Oncology; Financial Interests, Personal, Research Grant: GC Oncology; Financial Interests, Personal, Advisory Role: Invitae; Financial Interests, Personal, Other, Honoraria: Invitae; Financial Interests, Personal, Research Grant: Invitae; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Advisory Role: MDX Health; Financial Interests, Personal, Other, Honoraria: MDX Health; Financial Interests, Personal, Research Grant: MDX Health; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Personal, Other, Honoraria: Myovant; Financial Interests, Personal, Research Grant: Myovant; Financial Interests, Personal, Advisory Role: Myriad; Financial Interests, Personal, Other, Honoraria: Myriad; Financial Interests, Personal, Research Grant: Myriad; Financial Interests, Personal, Other, Honoraria: Nymox; Financial Interests, Personal, Advisory Role: Nymox; Financial Interests, Personal, Research Grant: Nymox; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Other, Honoraria: Propella Therapeutics; Financial Interests, Personal, Advisory Role: Propella Therapeutics; Financial Interests, Personal, Research Grant: Propella Therapeutics; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Other, Honoraria: Inozyme; Financial Interests, Personal, Advisory Role: Inozyme; Financial Interests, Personal, Research Grant: Inozyme; Financial Interests, Personal, Other, Honoraria: Sesen Bio; Financial Interests, Personal, Advisory Role: Sesen Bio; Financial Interests, Personal, Research Grant: Sesen Bio; Financial Interests, Personal, Other, Honoraria: Tolmar; Financial Interests, Personal, Advisory Role: Tolmar; Financial Interests, Personal, Research Grant: Tolmar; Financial Interests, Personal, Other, Honoraria: Cold genesys; Financial Interests, Personal, Advisory Role: Cold genesys; Financial Interests, Personal, Research Grant: Cold genesys; Financial Interests, Personal, Other, Honoraria: Exact Sciences; Financial Interests, Personal, Advisory Role: Exact Sciences; Financial Interests, Personal, Research Grant: Exact Sciences; Financial Interests, Personal, Other, Honoraria: Genesis Care; Financial Interests, Personal, Advisory Role: Genesis Care; Financial Interests, Personal, Research Grant: Genesis Care; Financial Interests, Personal, Other, Honoraria: Pacific Edge; Financial Interests, Personal, Advisory Role: Pacific Edge; Financial Interests, Personal, Research Grant: Pacific Edge; Financial Interests, Personal, Other, Honoraria: Phosphorus; Financial Interests, Personal, Advisory Role: Phosphorus; Financial Interests, Personal, Research Grant: Phosphorus; Financial Interests, Personal, Other, Honoraria: Urogen; Financial Interests, Personal, Advisory Role: Urogen; Financial Interests, Personal, Research Grant: Urogen; Financial Interests, Personal, Other, Honoraria: Specialty Networks; Financial Interests, Personal, Advisory Role: Specialty Networks; Financial Interests, Personal, Research Grant: Specialty Networks; Financial Interests, Personal, Other, Honoraria: Preview; Financial Interests, Personal, Advisory Role: Preview; Financial Interests, Personal, Research Grant: Preview; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Clovis Oncology; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Guardant; Financial Interests, Personal, Invited Speaker: Health foundation medicine. D. Dalal: Financial Interests, Institutional, Other, Employee: Novartis Pharmaceuticals. 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, Accommodations, Expenses: Janssen; Financial Interests, Personal, Other, Travel, Accommodations, 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. All other authors have declared no conflicts of interest.