1765O - 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. Treatment emergent adverse events (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 or 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: 1765O

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

Legal entity responsible for the study

Amgen.

Funding

Amgen.

Disclosure

W. Kelly: Financial Interests, Personal, Invited Speaker: 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. Danila: Financial Interests, Institutional, Research Grant: US Department of Defense, American Society of Clinical Oncology, American Society of Clinical Oncology, Stand Up 2 Cancer (MSKCC), Amgen (MSKCC), Janssen Research & Development (MSKCC), Astellas (MSKCC), Medivation (MSKCC), Medivation (MSKCC), Genentech (MSKCC), CreaTV (MSKCC); 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, Invited Speaker: Boehringer Ingelheim, Eli Lilly, Novartis, Roche; Financial Interests, Personal, Advisory Role: AbbVie, Bayer, Blueprint Medicines, Boehringer-Ingelheim, BMS, Daiichi Sankyo, Merck KGaA, Novartis, PharmaEngine, Rakuten; Financial Interests, Personal, Other, Travel support: BeiGene, Eli Lilly, Impact. J. Lee: Financial Interests, Personal, Stocks/Shares: Johnson & Johnson, Amgen, Merck, Innovent Biologics, Black Diamond Therapeutics, Karyopharm Therapeutics, Zymeworks; Financial Interests, Institutional, Research Grant: Pfizer, Janssen, Novartis, BMS, Roche, Genentech, AstraZeneca, MSD, Bayer Schering Pharma, Seagen, GI Innovation, Amgen, Oscotec; Financial Interests, Personal, Advisory Role: Merck, AstraZeneca, Sanofi Korea, Oscotec, Astellas Korea. N. Matsubara: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Role: Janssen, MSD, Eli Lilly; Financial Interests, Institutional, Research Grant: Janssen, AstraZeneca, Bayer, MSD, Taiho, Astellas, Amgen, Eisai, Eli Lilly, Takeda, Pfizer, Seagen, Chugai, AbbVie, Novartis. P. Ward: Financial Interests, Personal, Advisory Role: Amgen. A.J. Armstrong: Financial Interests, Institutional, Research Grant: Astellas, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Amgen; Financial Interests, Institutional, Principal Investigator: 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. 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, Invited Speaker: Astellas, MSD, Novartis; Financial Interests, Personal, Advisory Board: BMS/Ono Pharmaceutical, Eisai, Ipsen, MSD, Pfizer, Yuhan. T. Dorff: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Sanofi and Bayer. 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, GALAHADACIS Prevalence: 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, J. Connarn, J. Stieglmaier: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks or ownership: Amgen. G. Jurida: Financial Interests, Personal, Full or part-time Employment: Amgen. H. Penny: Financial Interests, Full or part-time Employment: Amgen. L.J. Appleman: Financial Interests, Personal, Advisory Board: AADi; Financial Interests, Personal, Research Funding: Janssen Oncology; Financial Interests, Institutional, Research Funding: Pfizer, Exelixis, BMS, Astellas Pharma, Novartis, Bayer, Merck, Genentech/Roche, AVEO, Peloton Therapeutics, Calithera Biosciences, Seattle Genetics, Inovio Pharmaceuticals, Eisai, Lilly, Amgen, Surface Oncology, BioNTech AG, Epizyme, Ipsen, Arvinas; Financial Interests, Personal, Other: Pfizer; Non-Financial Interests, Personal, Other: Exelixis. All other authors have declared no conflicts of interest.