Safety, clinical activity, and biological correlates of response in patients with metastatic melanoma: Results from a phase I trial of atezolizumab

Omid Hamid*, Luciana Molinero, Christopher R. Bolen, Jeffrey A. Sosman, Eva Muñoz-Couselo, Harriet M. Kluger, David F. McDermott, John D. Powderly, Indrani Sarkar, Marcus Ballinger, Marcella Fasso, Carol O'Hear, Daniel S. Chen, Priti S. Hegde, F. Stephen Hodi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)6061-6072
Number of pages12
JournalClinical Cancer Research
Issue number20
StatePublished - Oct 15 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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