Browsing by Author "Tran, Ben"

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    A Phase I Study of Acapatamab, a Half-life Extended, PSMA-Targeting Bispecific T-cell Engager for Metastatic Castration-Resistant Prostate Cancer
    (American Association for Cancer Research, 2024) Dorff, Tanya; Horvath, Lisa G.; Autio, Karen; Bernard-Tessier, Alice; Rettig, Matthew B.; Machiels, Jean-Pascal; Bilen, Mehmet A.; Lolkema, Martijn P.; Adra, Nabil; Rottey, Sylvie; Greil, Richard; Matsubara, Nobuaki; Tan, Daniel S. W.; Wong, Alvin; Uemura, Hiroji; Lemech, Charlotte; Meran, Johannes; Yu, Youfei; Minocha, Mukul; McComb, Mason; Penny, Hweixian Leong; Gupta, Vinita; Hu, Xuguang; Jurida, Gabor; Kouros-Mehr, Hosein; Janát-Amsbury, Margit M.; Eggert, Tobias; Tran, Ben; Medicine, School of Medicine
    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.
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    Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium
    (American Society of Clinical Oncology, 2021) Beyer, Jörg; Collette, Laurence; Sauvé, Nicolas; Daugaard, Gedske; Feldman, Darren R.; Tandstad, Torgrim; Tryakin, Alexey; Stahl, Olof; Gonzalez-Billalabeitia, Enrique; De Giorgi, Ugo; Culine, Stéphane; de Wit, Ronald; Hansen, Aaron R.; Bebek, Marko; Terbuch, Angelika; Albany, Costantine; Hentrich, Marcus; Gietema, Jourik A.; Negaard, Helene; Huddart, Robert A.; Lorch, Anja; Cafferty, Fay H.; Heng, Daniel Y. C.; Sweeney, Christopher J.; Winquist, Eric; Chovanec, Michal; Fankhauser, Christian; Stark, Daniel; Grimison, Peter; Necchi, Andrea; Tran, Ben; Heidenreich, Axel; Shamash, Jonathan; Sternberg, Cora N.; Vaughn, David J.; Duran, Ignacio; Bokemeyer, Carsten; Patrikidou, Anna; Cathomas, Richard; Assele, Samson; Gillessen, Silke; International Germ Cell Cancer Classification Update Consortium; Medicine, School of Medicine
    Purpose: The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. Materials and methods: Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients. Results: Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH. Conclusion: PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.