264P - Interim results from a phase I study of AMG 509 (xaluritamig), a STEAP1 x CD3 XmAb 2+1 immune therapy in patients with metastatic castration-resistant prostate cancer (mCRPC)

Background

Xaluritamig is a novel bispecific XmAb® 2+1 T-cell engager with two STEAP1 binding sites designed to facilitate T-cell–mediated lysis of STEAP1-expressing cells. We report results from the dose exploration of xaluritamig monotherapy in a first-in-human study for patients (pts) with mCRPC.

Methods

Eligible pts had mCRPC refractory to prior novel hormonal therapy and 1–2 taxane regimens, ECOG 0–1, and adequate organ function. Xaluritamig was administered as an IV weekly (QW) or Q2W with various dose levels/schedules (DLs). Study objectives were to evaluate safety, tolerability, antitumor activity, PK, and determine the MTD and RP2D.

Results

As of 23 March 2023, 97 pts in 15 DLs received ≥1 dose of xaluritamig. Median (range) age was 67 (40–86) years; 67 pts (69.1%) had received > 3 prior lines of therapy. TEAEs were reported in 100% of pts (grade ≥3, 74.2%); 95.9% reported treatment-related AEs (TRAEs) (grade ≥3, 52.6%). The most common AEs were cytokine release syndrome (CRS; 72.2%), fatigue (52.6%), anemia (45.4%), pyrexia (40.2%), and myalgia (39.2%). CRS was primarily grade 1/2, one event being grade 3 (no grade 4/5 CRS; cycle 1). In the DL15 QW cohort, 3 of 6 DLT evaluable subjects experienced DLTs, defining DL14 QW as the MTD. TRAEs leading to discontinuation occurred in 17.5% of pts. PSA50 (≥ 50% PSA decline) responses occurred in 42 pts (47.2%); PSA90, in 24 pts (27.0%) (Table). PSA responses were more frequent at higher DLs (DL8–15) than in lower DLs (DL1–7). Overall, RECIST responses included 15 (22.7%) confirmed PR and 30 (45.5%) SD. At higher DLs, 14 pts (38.9%) had confirmed PR and 12 (33.3%) SD. Preliminary PK showed dose-proportional increase in exposure with a mean terminal half-life of approximately 3-4 days. Table: 264P

Conclusions

Xaluritamig was tolerable with low-grade CRS (occurring primarily cycle 1) with encouraging preliminary efficacy in heavily pretreated pts with mCRPC.

Clinical trial identification

NCT04221542.

Editorial acknowledgement

Yin Lin, an employee of Amgen Inc., provided medical writing assistance.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

W.K. Kelly: Financial Interests, Personal, Financially compensated role: Janssen Oncology; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Institutional, Research Funding: Novartis, Janssen Oncology, Bayer, Exelixis, Seattle Genetics, Endocyte, Amgen, BioClin Therapeutics, Sarah Cannon Research Institute, Hoffman-LaRoche, Regeneron; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen Oncology. D.C. Danila: Financial Interests, Personal, Research Grant: US Department of Defense (DD), American Society of Clinical Oncology (DD), Prostate Cancer Foundation (DD), Stand Up 2 Cancer (MSKCC), Amgen (MSKCC), Janssen Research & Development (MSKCC), Astellas (MSKCC), Medivation, (MSKCC) Agensys (MSKCC), Genentech ; Financial Interests, Personal, Advisory Role: Angle LLT, Axiom LLT, Janssen Research & Development, AstraZeneca, BioView LTD, Clovis, Astellas, Medivation, Pfizer, Agensys, Merck. C. Lin: Financial Interests, Personal, Other, Travel support: BeiGene, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo, Novartis, AbbVie, PharmaEngine, Merck KGaA, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Roche; Financial Interests, Personal, Other, Travel Support: IMPACT Therapeutics. J. Lee: Financial Interests, Personal, Advisory Board: Astellas Korea, AstraZeneca, Bristol Myers Squibb Korea, MSD, Merck; Financial Interests, Personal, Stocks/Shares: Merck, Johnson and Johnson, Amgen, Black Diamond Therapeutics, Zymeworks, Karyopharm Therapeutics; Financial Interests, Institutional, Local PI: Pfizer, Janssen, Novartis, Bristol Myers Squibb, Genetech, Roche, AstraZeneca, MSD, Merck, Bayer Shering Pharma, Seagen, GI Innovation, Amgen, Oscotec. N. Matsubara: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Coordinating PI: Janssen, Roche, MSD, Taiho, Pfizer, Chugai; Financial Interests, Institutional, Local PI: AstraZeneca, Bayer, Astellas, Amgen, Esai, Eli Lilly, Avbbie. P.J. Ward: Financial Interests, Personal, Advisory Board: Amgen. A.J. Armstrong: Financial Interests, Institutional, Research Funding: Astellas, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Amgen; Financial Interests, Institutional, Coordinating PI: Novartis ; Financial Interests, Personal, Advisory Role: Astellas, Epic Sciences, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Clovis, Exact Sciences, Myovant, Exelixis, GoodRx, Novartis. D.W. Pook: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: BMS, MSD, Ipsen, Pfizer, Eisai, Astellas; Financial Interests, Institutional, Local PI: BMS, Astellas, Roche, MSD, Amgen; Financial Interests, Institutional, Coordinating PI: Pfizer, Ipsen. M. Kim: Financial Interests, Personal, Advisory Board: Ipsen, Bristol Myers Squibb/Ono Pharmaceutical, Eisai, Yuhan, MSD, Pfizer; Financial Interests, Personal, Invited Speaker: Norvatis, Astellas, MSD. T. Dorff: Financial Interests, Institutional, Advisory Board: Exelixis; Financial Interests, Personal, Other, drafted educational content (unbranded): Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Sanofi. S. Fischer: Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Advisory Role: Ipsen. L.G. Horvath: Financial Interests, Personal, Advisory Board, Honorarium donated back to Chris O'Brien Lifehouse (My hospital): Imagion Biosystems; Financial Interests, Institutional, Invited Speaker: Astellas, Janssen, Amgen; Financial Interests, Institutional, Advisory Board: Astellas, Bayer; Financial Interests, Personal, Member of Board of Directors, No payment: ANZUP (Australia and New Zealand Urogenital and Prostate) Clinical Trials Group; Financial Interests, Personal, Stocks/Shares, Stock options: Imagion Biosystems; Financial Interests, Personal, Stocks/Shares: My Emergency Doctor; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Local PI, MK7684-001MK3475-991: MSD; Financial Interests, Institutional, Local PI, AMG160 Phase 1AMG509 Phase 1AMG757 Phase 1: Amgen; Financial Interests, Institutional, Local PI, 9785-CL-0335 (ARCHES): Astellas; Financial Interests, Institutional, Local PI, SHR3680-002: Jiangsu Hengrui Medicines; Financial Interests, Institutional, Local PI, TALAPRO2, TALAPRO3: Pfizer; Financial Interests, Institutional, Local PI, CYCLONE-2, CYCLONE-3: Eli Lilly; Financial Interests, Institutional, Steering Committee Member, ENZAMET, ENZARAD, DASL-HiCAP, GUIDE, ANZAdapt: ANZUP; Financial Interests, Institutional, Local PI, GALAHADACISPrevalence: Janssen-Cilag; Financial Interests, Institutional, Local PI, GSK204697: GSK; Financial Interests, Institutional, Local PI, XL184-021: Exelexis; Financial Interests, Institutional, Local PI, BGB-A317BGB-283BGB-A317-290: BeiGene; Financial Interests, Institutional, Local PI, FPT155-001: Five Prime; Financial Interests, Institutional, Local PI, AB928CSP0003: ARCUS; Financial Interests, Institutional, Local PI, ATG-017 and ATG-019: Antagene; Financial Interests, Institutional, Local PI, JANUX007: Janux; Financial Interests, Institutional, Local PI, ENZAMET, ENZA-P, Upfront PSMA, ANZAdapt, GUIDE: ANZUP; Financial Interests, Institutional, Local PI, HP-518-CS-001: Hinova; Financial Interests, Institutional, Local PI, Petranha: AstraZeneca. Z. Yang: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. G. Jurida, J. Connarn, J. Stieglmaier: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks/Shares, Stockholder: Amgen. L.J. Appleman: Financial Interests, Personal, Advisory Board: AADi; Financial Interests, Personal, Research Funding: Janssen Oncology; Financial Interests, Institutional, Research Funding: Pfizer, Exelixis, Bristol Myers Squibb, Astellas Pharma, Novartis, Bayer, Merck, Genentech/Roche, AVEO, Peloton Therapeutics, Calithera Biosciences, Seattle Genetics, Inovio Pharmaceuticals, Eisai, Lilly, Amgen, Surface Oncology, BioNTech AG, Epizyme, Ips; Other, Personal, Other: Pfizer; Non-Financial Interests, Personal, Non remunerated activity: Exelixis. All other authors have declared no conflicts of interest.