Omid Hamid 1 , Luciana Molinero 2 , Christopher R Bolen 2 , Jeffrey A Sosman 3 , Eva Muñoz-Couselo 4 , Harriet M Kluger 5 , David F McDermott 6 , John D Powderly 7 , Indrani Sarkar 2 , Marcus Ballinger 2 , Marcella Fassò 2 , Carol O'Hear 2 , Daniel S Chen 2 , Priti S Hegde 2 , F Stephen Hodi 8 Show Affiliations »
Abstract
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PURPOSE: Atezolizumab [anti-programmed death-ligand 1 (PD-L1 )] selectively targets PD-L1 to block its interaction with receptors programmed death 1 and B7.1, thereby reinvigorating antitumor T-cell activity. We evaluated the long-term safety and activity of atezolizumab , along with biological correlates of clinical activity endpoints, in a cohort of patients with melanoma in an ongoing phase Ia study (NCT01375842). PATIENTS AND METHODS: Patients with unresectable or metastatic melanoma were enrolled to receive atezolizumab 0.1 to 20 mg/kg or ≥10 mg/kg every 3 weeks. Primary study objectives were safety and tolerability . Secondary objectives included investigator-assessed efficacy measures; pharmacodynamic and predictive biomarkers of antitumor activity were explored. RESULTS: Forty-five patients were enrolled and were evaluable for safety . Most treatment-related adverse events (AE) were grade 1/2 (60%). Fatigue (44%), pruritus (20%), pyrexia (18%), and rash (18%) were the most common treatment-related AEs of any grade. No treatment-related deaths occurred. Overall response rate was 30% among 43 efficacy- evaluable patients, with a median duration of response of 62 months [95% CI, 35-not estimable (NE)]. Clinically meaningful long-term survival was observed, with a median overall survival of 23 months (95% CI, 9-66). Baseline biomarkers of tumor immunity [PD-L1 expression on immune cells, T effector (Teff), and antigen presentation gene signatures) and tumor mutational burden (TMB ) were associated with improved response, progression-free survival, and overall survival . CONCLUSIONS: Atezolizumab was well tolerated, with durable responses and survival in patients with melanoma . PD-L1 expression, TMB, and Teff signatures may indicate improved benefit with atezolizumab in these patients. ©2019 American Association for Cancer Research.
RCT Entities: Population
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Outcomes
PURPOSE: Atezolizumab [anti-programmed death-ligand 1 (PD-L1 )] selectively targets PD-L1 to block its interaction with receptors programmed death 1 and B7.1 , thereby reinvigorating antitumor T-cell activity. We evaluated the long-term safety and activity of atezolizumab , along with biological correlates of clinical activity endpoints, in a cohort of patients with melanoma in an ongoing phase Ia study (NCT01375842). PATIENTS AND METHODS: Patients with unresectable or metastatic melanoma were enrolled to receive atezolizumab 0.1 to 20 mg/kg or ≥10 mg/kg every 3 weeks. Primary study objectives were safety and tolerability. Secondary objectives included investigator-assessed efficacy measures; pharmacodynamic and predictive biomarkers of antitumor activity were explored. RESULTS: Forty-five patients were enrolled and were evaluable for safety. Most treatment-related adverse events (AE) were grade 1/2 (60%). Fatigue (44%), pruritus (20%), pyrexia (18%), and rash (18%) were the most common treatment-related AEs of any grade. No treatment-related deaths occurred. Overall response rate was 30% among 43 efficacy- evaluable patients , with a median duration of response of 62 months [95% CI, 35-not estimable (NE)]. Clinically meaningful long-term survival was observed, with a median overall survival of 23 months (95% CI, 9-66). Baseline biomarkers of tumor immunity [PD-L1 expression on immune cells, T effector (Teff), and antigen presentation gene signatures) and tumor mutational burden (TMB ) were associated with improved response, progression-free survival, and overall survival. CONCLUSIONS: Atezolizumab was well tolerated, with durable responses and survival in patients with melanoma . PD-L1 expression, TMB , and Teff signatures may indicate improved benefit with atezolizumab in these patients . ©2019 American Association for Cancer Research.
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Year: 2019
PMID： 31358540 DOI： 10.1158/1078-0432.CCR-18-3488
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531