A Phase I Study of Acapatamab, a Half-life Extended, PSMA-Targeting Bispecific T-cell Engager for Metastatic Castration-Resistant Prostate Cancer
- Author(s)
- Dorff, T; Horvath, LG; Autio, K; Bernard-Tessier, A; Rettig, MB; Machiels, JP; Bilen, MA; Lolkema, MP; Adra, N; Rottey, S; Greil, R; Matsubara, N; Tan, DSW; Wong, A; Uemura, H; Lemech, C; Meran, J; Yu, Y; Minocha, M; McComb, M; Penny, HL; Gupta, V; Hu, X; Jurida, G; Kouros-Mehr, H; Janát-Amsbury, MM; Eggert, T; Tran, B;
- Details
- Publication Year 2024-04-15,Volume 30,Issue #8,Page 1488-1500
- Journal Title
- Clinical Cancer Research
- Publication Type
- Research article
- Abstract
- PURPOSE: Safety and efficacy of acapatamab, a prostate-specific membrane antigen (PSMA) x CD3 bispecific T-cell engager were evaluated in a first-in-human study in metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Patients with mCRPC refractory to androgen receptor pathway inhibitor therapy and taxane-based chemotherapy received target acapatamab doses ranging from 0.003 to 0.9 mg in dose exploration (seven dose levels) and 0.3 mg (recommended phase II dose) in dose expansion intravenously every 2 weeks. Safety (primary objective), pharmacokinetics, and antitumor activity (secondary objectives) were assessed. RESULTS: In all, 133 patients (dose exploration, n = 77; dose expansion, n = 56) received acapatamab. Cytokine release syndrome (CRS) was the most common treatment-emergent adverse event seen in 97.4% and 98.2% of patients in dose exploration and dose expansion, respectively; grade ≥ 3 was seen in 23.4% and 16.1%, respectively. Most CRS events were seen in treatment cycle 1; incidence and severity decreased at/beyond cycle 2. In dose expansion, confirmed prostate-specific antigen (PSA) responses (PSA50) were seen in 30.4% of patients and radiographic partial responses in 7.4% (Response Evaluation Criteria in Solid Tumors 1.1). Median PSA progression-free survival (PFS) was 3.3 months [95% confidence interval (CI): 3.0-4.9], radiographic PFS per Prostate Cancer Clinical Trials Working Group 3 was 3.7 months (95% CI: 2.0-5.4). Acapatamab induced T-cell activation and increased cytokine production several-fold within 24 hours of initiation. Treatment-emergent antidrug antibodies were detected in 55% and impacted serum exposures in 36% of patients in dose expansion. CONCLUSIONS: Acapatamab was safe and tolerated and had a manageable CRS profile. Preliminary signs of efficacy with limited durable antitumor activity were observed. Acapatamab demonstrated pharmacokinetic and pharmacodynamic activity.
- Publisher
- American Association for Cancer Research
- Keywords
- Male; Humans; *Prostatic Neoplasms, Castration-Resistant/pathology; Prostate-Specific Antigen; Half-Life; Treatment Outcome; *Antineoplastic Agents/therapeutic use; Androgen Receptor Antagonists/therapeutic use; T-Lymphocytes/metabolism
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1158/1078-0432.Ccr-23-2978
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-07-04 04:51:21
Last Modified: 2024-07-04 04:51:28