Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial.
Eugene ShenderovAngelo M DeMarzoTamara L LotanHao WangSin ChanSu Jin LimHongkai JiMohamad E AllafCarolyn ChapmanPaul A MooreFrancine ChenKristina SorgAndrew M WhiteSarah E ChurchBriana HudsonPaul A FieldsShaohui HuSamuel R DenmeadeKenneth J PientaChristian P PavlovichAshley E RossCharles G DrakeDrew M PardollEmmanuel S AntonarakisPublished in: Nature medicine (2023)
B7 homolog 3 (B7-H3; CD276), a tumor-associated antigen and possible immune checkpoint, is highly expressed in prostate cancer (PCa) and is associated with early recurrence and metastasis. Enoblituzumab is a humanized, Fc-engineered, B7-H3-targeting antibody that mediates antibody-dependent cellular cytotoxicity. In this phase 2, biomarker-rich neoadjuvant trial, 32 biological males with operable intermediate to high-risk localized PCa were enrolled to evaluate the safety, anti-tumor activity and immunogenicity of enoblituzumab when given before prostatectomy. The coprimary outcomes were safety and undetectable prostate-specific antigen (PSA) level (PSA 0 ) 1 year postprostatectomy, and the aim was to obtain an estimate of PSA 0 with reasonable precision. The primary safety endpoint was met with no notable unexpected surgical or medical complications, or surgical delay. Overall, 12% of patients experienced grade 3 adverse events and no grade 4 events occurred. The coprimary endpoint of the PSA 0 rate 1 year postprostatectomy was 66% (95% confidence interval 47-81%). The use of B7-H3-targeted immunotherapy in PCa is feasible and generally safe and preliminary data suggest potential clinical activity. The present study validates B7-H3 as a rational target for therapy development in PCa with larger studies planned. The ClinicalTrials.gov identifier is NCT02923180.
Keyphrases
- prostate cancer
- radical prostatectomy
- rectal cancer
- end stage renal disease
- lymph node
- locally advanced
- ejection fraction
- newly diagnosed
- cancer therapy
- chronic kidney disease
- clinical trial
- healthcare
- radiation therapy
- randomized controlled trial
- stem cells
- study protocol
- machine learning
- electronic health record
- tyrosine kinase
- drug delivery
- robot assisted
- insulin resistance
- minimally invasive
- risk assessment
- data analysis
- big data
- patient reported outcomes