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Clinical Trial
. 2018 Nov;13(11):1733-1742.
doi: 10.1016/j.jtho.2018.05.004.

FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1-Selected Patients With NSCLC

David R Spigel  1 , Jamie E Chaft  2 , Scott Gettinger  3 , Bo H Chao  4 , Luc Dirix  5 , Peter Schmid  6 , Laura Q M Chow  7 , Rodney J Hicks  8 , Larry Leon  9 , Jill Fredrickson  9 , Marcin Kowanetz  9 , Alan Sandler  9 , Roel Funke  9 , Naiyer A Rizvi  10
Affiliations
Clinical Trial

FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1-Selected Patients With NSCLC

David R Spigel et al. J Thorac Oncol. 2018 Nov.

Abstract

Introduction: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced NSCLC selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression.

Methods: Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into cohort 1 (chemotherapy-naive/>6 months between adjuvant chemotherapy and recurrence), cohort 2 (≥ second-line without brain metastases), or cohort 3 (≥ second-line with treated brain metastases). Patients received 1200 mg atezolizumab on day 1 (21-day cycles). Primary endpoint was investigator-assessed modified Response Evaluation Criteria in Solid Tumors, objective response rate (Response Evaluation Criteria in Solid Tumors v1.1). Secondary endpoints were overall survival, progression-free survival, duration of response, and safety.

Results: Patients (N = 138) were enrolled (137 evaluable for response: cohort 1, n = 31; cohort 2, n = 93; and cohort 3, n = 13). Investigator-assessed objective response rate was 32%, 21%, and 23% for cohorts 1, 2, and 3, respectively. Treatment-related adverse events were reported in 81%, 67%, and 69% of patients, respectively, including grade 3-4 treatment-related adverse events in 16%, 19%, and 15%, respectively. Moreover, 88.6% (86 of 97) paired baseline tumor samples had <5% change in TC/IC PD-L1 expression over time.

Conclusions: Atezolizumab monotherapy showed clinical activity in patients with NSCLC, including those with brain metastases; safety was consistent with previous trials. Atezolizumab has completed phase III monotherapy studies in second-line. Front-line trials are ongoing, confirming these favorable results.

Keywords: Anti–PD-L1; Immunotherapy; NSCLC.

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Figures

Figure 1.
Figure 1.
Study design. AE, adverse event; PD, progressive disease
Figure 2.
Figure 2.
Kaplan–Meier curves of progression-free survival (A) and overall survival (B) by RECIST v1.1.
See this image and copyright information in PMC

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