Abstract 647TiP
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 the surrounding microenvironment. Androgen receptor pathway inhibitors (ARPI) may alter PSMA expression and radiosensitivity. PSMAddition will assess the efficacy and safety of 177Lu-PSMA-617 plus standard of care (SOC) versus SOC alone in adults with metastatic hormone-sensitive prostate cancer (mHSPC).
Trial design
PSMAddition (NCT04720157) is an international prospective open-label, randomized, phase III trial in adults with mHSPC. Eligible patients are treatment-naïve or minimally treated candidates for hormonal therapy, with PSMA-positive disease (determined by [68Ga]Ga-PSMA-11 PET/CT), ECOG performance status of 0 to 2 and adequate major organ function. Patients are excluded if they have rapidly progressing tumours that require chemotherapy. Approximately 1126 patients will be randomized 1:1 to receive 177Lu-PSMA-617 (7.4 GBq i.v. every 6 weeks, ≤ 6 cycles) plus SOC or SOC alone (control arm). SOC is ARPI and androgen deprivation therapy. Stratification factors are tumour volume (high/low), age (≥ 70/< 70 years) and previous/planned prostatectomy or radiation treatment of the primary prostate tumour (yes/no). The primary endpoint is radiographic progression-free survival (rPFS), as assessed by blinded independent centralized review. Upon centrally confirmed radiographic progression, participants in the control arm can cross over to the 177Lu-PSMA-617 arm. The planned sample size provides 95% power to detect a hazard ratio of 0.7 for rPFS after 418 events with an overall one-sided significance level of 0.025. The key secondary endpoint is overall survival. Other secondary endpoints are the proportion of patients with a prostate-specific antigen (PSA) decline of ≥ 90% from baseline, time to development of metastatic castration resistant prostate cancer, composite progression-free survival (radiographic, clinical or PSA progression), safety and tolerability, and health-related quality of life.
Clinical trial identification
CAAA617C12301; EudraCT 2020-003968-56.
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
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; 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: Genomic Health; Financial Interests, Personal, Advisory Role: POINT Biopharma; Financial Interests, Personal, Advisory Role: Blue Earth Diagnostics; Financial Interests, Personal, Advisory Role: Seattle Genetics; 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; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Institutional, Funding: Clovis Oncology; Financial Interests, Personal, Other, Uncompensated Relationships: Telix Pharmaceuticals; Financial Interests, Personal, Other, Uncompensated Relationships: ATLAB Pharma; Financial Interests, Personal, Other, Uncompensated Relationships: Phosplatin Therapeutics. 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, Institutional, Funding: SOTIO; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Progenics. F. Saad: Financial Interests, Personal, Writing Engagements: Novartis Pharmaceuticals; Financial Interests, Personal, Funding: Novartis Pharmaceuticals; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Myovant; Financial Interests, Personal, Research Grant: Astellas; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Myovant; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. O. Sakharova: Financial Interests, Personal, Full or part-time Employment: 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, 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. F. Feng: Financial Interests, Personal, Writing Engagements: Novartis Pharmaceuticals; Financial Interests, Personal, Research Grant, Payments to institution: Zenith; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Personal, Advisory Role: Roivant; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Foundation Medicine; Financial Interests, Personal, Stocks/Shares, owned stock in PFS Genomics, a company that I founded, which was sold to Exact Sciences: PFS Genomics; Financial Interests, Personal, Stocks/Shares: SerImmune; Financial Interests, Personal, Advisory Board: SerImmune. 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. 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.