Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Phase Ib Trial of Bavdegalutamide (ARV-110) in Combination with Abiraterone for Metastatic Prostate Cancer.
СтатьяКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Smoragiewicz Martin, Bernard-Tessier Alice, Linch Mark, Shen John, Shore Neal D, Parikh Omi, Chi Kim N, Sokolova Alexandra O, Culine Stephane, McKean Meredith, Gleave Martin, Devitt Michael E, Zhi Eric, Gong Jiachang, Landrette Sean, Colasanto Meghan, Patel Vaibhav, Gao Xin
Аннотация
PURPOSE: Resistance to androgen receptor (AR) pathway inhibitors necessitates the development of regimens to improve outcomes in metastatic prostate cancer (mPC). This phase Ib clinical trial evaluated the safety/tolerability and pharmacokinetics of bavdegalutamide, an oral proteolysis-targeting chimera AR degrader, combined with abiraterone in patients with mPC experiencing prostate-specific antigen (PSA) progression on abiraterone.
PATIENTS AND METHODS: Patients received bavdegalutamide 420 mg, abiraterone ≤1,000 mg, and corticosteroid daily. Assessments included safety [dose-limiting toxicities (DLT); treatment-emergent adverse events (TEAE)], pharmacokinetics, PSA control rate, ≥50% PSA decline (PSA50), and radiographic progression-free survival (rPFS).
RESULTS: Forty-five patients were treated; seven had AR ligand-binding domain (LBD) mutations. The median duration of exposure was 35.7 weeks; 13 patients were continuing bavdegalutamide at the data cutoff. No DLTs were observed. There were no clinically significant effects of bavdegalutamide on abiraterone pharmacokinetics. Bavdegalutamide 420 mg daily was selected as the recommended phase II dose. TEAEs were mostly grade 1/2 (82.2%), and 17.8% were grade 3. Dose modifications or discontinuations due to TEAEs occurred in 48.9% and 13.3% of patients, respectively. The most common bavdegalutamide-related TEAEs were fatigue (48.9%) and nausea (46.7%). The PSA control rate was 48.9% [95% confidence interval (CI), 33.7-64.2]. The PSA50 response rate was 24.4% (95% CI, 12.9-39.5), including in five out of seven patients with AR LBD mutations. The median time to PSA progression was 2.8 months (95% CI, 1.5-6.5). The median rPFS was 16.3 months (95% CI, 8.2-not calculable).
CONCLUSIONS: Bavdegalutamide combined with abiraterone demonstrated a manageable safety profile with no major drug-drug interactions and evidence of clinical activity in mPC.
PATIENTS AND METHODS: Patients received bavdegalutamide 420 mg, abiraterone ≤1,000 mg, and corticosteroid daily. Assessments included safety [dose-limiting toxicities (DLT); treatment-emergent adverse events (TEAE)], pharmacokinetics, PSA control rate, ≥50% PSA decline (PSA50), and radiographic progression-free survival (rPFS).
RESULTS: Forty-five patients were treated; seven had AR ligand-binding domain (LBD) mutations. The median duration of exposure was 35.7 weeks; 13 patients were continuing bavdegalutamide at the data cutoff. No DLTs were observed. There were no clinically significant effects of bavdegalutamide on abiraterone pharmacokinetics. Bavdegalutamide 420 mg daily was selected as the recommended phase II dose. TEAEs were mostly grade 1/2 (82.2%), and 17.8% were grade 3. Dose modifications or discontinuations due to TEAEs occurred in 48.9% and 13.3% of patients, respectively. The most common bavdegalutamide-related TEAEs were fatigue (48.9%) and nausea (46.7%). The PSA control rate was 48.9% [95% confidence interval (CI), 33.7-64.2]. The PSA50 response rate was 24.4% (95% CI, 12.9-39.5), including in five out of seven patients with AR LBD mutations. The median time to PSA progression was 2.8 months (95% CI, 1.5-6.5). The median rPFS was 16.3 months (95% CI, 8.2-not calculable).
CONCLUSIONS: Bavdegalutamide combined with abiraterone demonstrated a manageable safety profile with no major drug-drug interactions and evidence of clinical activity in mPC.