1611P - Haematologic impact of [177Lu]Lu-PSMA-617 versus ARPI change in patients with metastatic castration-resistant prostate cancer in PSMAfore

Background

In PSMAfore (NCT04689828), [¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617) prolonged rPFS versus androgen receptor pathway inhibitor (ARPI) change with a favourable safety profile in taxane-naive patients with metastatic castration-resistant prostate cancer (mCRPC). We report the incidence, risk factors and management of haematologic treatment emergent adverse events (TEAEs).

Methods

Adults with PSMA-positive mCRPC and one progression on prior ARPI were randomized 1:1 to ¹⁷⁷Lu-PSMA-617 (7.4 GBq Q6W; 6 cycles) or ARPI change. The primary endpoint was rPFS; secondary endpoints included frequency of TEAEs and safety laboratory assessments. Haematologic TEAEs (CTCAE v5.0 coding) were grouped by MedDRA v26.1 terms. Baseline metastatic bone disease was assessed by bone scan. Baseline, on-treatment and follow-up haematology were assessed. The safety analysis set and 27 February 2024 data cutoff (third interim OS analysis) were used.

Results

Incidences of haematologic TEAEs were higher among patients receiving ¹⁷⁷Lu-PSMA-617 than ARPI change (Table). For ¹⁷⁷Lu-PSMA-617 versus ARPI change, haematologic TEAE incidences were 33/109 (30.3%) versus 22/113 (19.5%) in patients with ≤5 metastatic bone lesions and 53/118 (44.9%) versus 32/119 (26.9%) in patients with >5 bone lesions; incidence did not increase for patients receiving 5/6 versus 1–4 doses of ¹⁷⁷Lu-PSMA-617. For ¹⁷⁷Lu-PSMA-617 versus ARPI change: 29 patients (12.8%) versus 28 (12.1%) received blood transfusions (on-treatment: 19 [8.4%] vs 26 [11.2%]); 4 (1.8%) versus 3 (1.3%) received erythropoietin; 3 (1.3%) versus 0 received granulocyte colony stimulating factors.

Conclusions

Despite higher incidences of haematologic TEAEs among patients receiving ¹⁷⁷Lu-PSMA-617 compared with ARPI change, rates of complications or need for management of haematologic TEAEs were low and similar between treatment arms. Table: 1611P

DCO 27 Feb 2024^aRelated TEAEs as reported in the CRF are combined; patients are counted once per preferred term Febrile neutropenia: ^bn=2; ^cn=0

Clinical trial identification

NCT04689828, Protocol release date: 21 Feb 2023.

Editorial acknowledgement

Under direction of the authors, Katie Willetts, PhD, of Oxford PharmaGenesis, Oxford, UK provided medical writing support, which was funded by Novartis.

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

K.N. Chi: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, Point Biopharma, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, BMS; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Janssen, Novartis, Roche; Financial Interests, Institutional, Trial Chair: AstraZeneca, Arvinas, Janssen, Novartis; Financial Interests, Institutional, Local PI: Arvinas. O. Sartor: Financial Interests, Personal, Writing Engagement: Novartis; Financial Interests, Institutional, Research Grant: AAA, Amgen, AstraZeneca, Bayer, Endocyte, Invitae, Janssen, Lantheus, Merck, Progenics, and Tenebio; Financial Interests, Personal, Speaker, Consultant, Advisor: ARTBIO, AAA, AstraZeneca, Bayer, Blue Earth Diagnostics, Clarity Pharmaceuticals, Fusion, Isotopen Technologien Muenchen, Merck, Janssen, Myovant, Myriad, Noria Therapeutics, Novartis, NorthStar, POINT Biopharma, Pfizer, Sanofi, Tenebio, and Telix; Financial Interests, Personal, Other: Lantheus, Novartis, and NorthStar;; Financial Interests, Personal, Advisory Board: AstraZeneca, Merck, and Pfizer; Financial Interests, Personal, Stocks or ownership: Artbio, Ratio, Clarity, Convergent, Fusion, Lilly, Pfizer, Telix. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Personal, Advisory Board, February 2022: Arvinas; Financial Interests, Personal, Advisory Board, April 2022: Macrogenics; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the CAPITELLO 281 phase 3 trial: AstraZeneca; Non-Financial Interests, Principal Investigator, Chair of the TALAPRO-2 and TALAPRO-3 phase 3 trials: Pfizer; Non-Financial Interests, Principal Investigator, Chair of the RADIANT phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the TRITON-3 phase 3 trial: Clovis. J.S. de Bono: Financial Interests, Personal, Advisory Board: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi Sankyo, Eisai, Genentech Roche, Genmab, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals, Menarini Silicon Biosystems, ImCheck Therapeutics, Crescendo, MetaCurUm, Myricx, Nurix Therapeutics, Oncternal Therapeutics; Financial Interests, Institutional, Advisory Board: Harpoon, Dark Blue Therapeutics, Novartis, Takeda, Tango Therapeutics; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Bayer, Cellcentric, Daiichi Sankyo, Genentech Roche, Genmab, GSK, Harpoon, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Sanofi Aventis, Sierra Oncology, Taiho, Vertex Pharmaceuticals, Crescendo Biologics, Menarini Silicon Biosystems, Immunic Therapeutics, MetaCurUm, Myricx, Nurix Therapeutics, Oncternal Therapeutics; Financial Interests, Institutional, Local PI: Amgen; Non-Financial Interests, Principal Investigator: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi Sankyo, Eisai, Genentech Roche, Genmab, GSK, Harpoon, Janssen, Menarini Silicon Biosystems, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals, Crescendo, ImCheck Therapeutics, Immunic Therapeutics; Non-Financial Interests, Institutional, Product Samples: Daiichi Sankyo, Bayer, Merck Serono, AstraZeneca, Harpoon, Pfizer, Sierra Oncology, Genentech/Roche, Sanofi Aventis, GSK. 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Shore: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Cold Genesys, Dendreon, Exact Imaging, Genesis Care Us, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Propella, Sanofi Genzyme, Speciality Networks, Tolmar, Urogen, Clarity, Lantheus, Lilly, Photocure, Telix, Photocure, Asieris, Alessa Therapeutics, Arquer, Fize medical, GConcology, Guardant, Ferring, Foundation Medicine, Immunitybio, Incyte, Minomic, NGM, Nonagen, Novartis, PlatformQ, Promaxo, Protara, Accord, Antev, Aura biosciences, Sumitomo; Financial Interests, Personal, Member of Board of Directors: Photocure, Alessa Theraputics; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Bayer, Aura, Exact Imaging, Janssen, Merck, Myovant, Novartis, Pfizer, Propella, Bristol Myers Squibb, Dendreon, Pfizer, Urogen; Financial Interests, Institutional, Local PI: Alessa, GC Oncology, FORMA therapeutics, Pacific edge, Point Biopharma, The MT group, Theralase, Verity, Astellas, Palette Life Sciences, Steba, Zenflow. 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Kim: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor, Research, Speaker fees and travel: Varian; Financial Interests, Personal, Ownership Interest: GlobalART. M. Schweizer: Financial Interests, Personal, Advisory Board: Sanofi, AstraZeneca; Financial Interests, Personal, Other, Consultant: PharmaIn; Financial Interests, Institutional, Local PI: Zenith Epigenetics, BMS, Merck, Janssen, Pfizer, F. Hoffmann-La Roche, Tmunity, Epigenetix, Incyte, Ambrx Inc.; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Signal One. S. Alanee: Financial Interests, Personal, Full or part-time Employment: Novartis Oncology. S. Ghebremariam: Financial Interests, Personal, Full or part-time Employment: Novartis Oncology. M. Hertelendi: Financial Interests, Personal, Full or part-time Employment: Novartis Oncology. M.J. 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