Safety and clinical activity of durvalumab (MEDI4736), an anti-PD-L1 antibody, in treatment-naïve patients with advanced non‒small-cell lung cancer.
2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2016.34.15_suppl.9029
ISSN1527-7755
AutoresScott Antonia, Sang–We Kim, Alexander I. Spira, Myung‐Ju Ahn, Sai‐Hong Ignatius Ou, Neda Stjepanovic, A. Fasolo, Dirk Jäger, Patrick A. Ott, Zev A. Wainberg, Heather A. Wakelee, Jonathan W. Goldman, John F. Kurland, Marlon C. Rebelatto, Wenliang Yao, Ashok Gupta, John A. Blake-Haskins, Neil H. Segal,
Tópico(s)Cancer Cells and Metastasis
Resumo9029 Background: The PD-1/PD-L1 axis is an important immune inhibitory pathway contributing to tumor cell escape from immunosurveillance. A Phase 1/2 dose escalation and dose expansion study is ongoing to evaluate the safety and efficacy of durvalumab, a modified human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, in patients with advanced non‒small-cell lung cancer (NSCLC) or other solid tumor types. Methods: Durvalumab 10 mg/kg is given q2w for up to 12 months to treatment-naïve patients with histologically or cytologically documented Stage IIIB/IV squamous (SQ) or non-SQ NSCLC. Retreatment is permitted if disease progresses after 12 months of therapy. Response is investigator-assessed per RECIST v1.1, and the results are presented by histology and PD-L1 status with the Ventana SP263 assay (PD-L1+ defined as ≥ 25% of tumor cells expressing membrane PD-L1). Fifteen patients were initially enrolled regardless of PD-L1 status. After a protocol amendment, enrollment was restricted to PD-L1+ patients. Results: As of 14 Dec 2015, 59 patients (48 PD-L1+; 9 PD-L1-; 58 EGFR WT; 57 ALK WT; 55 KRAS WT; 29 SQ; 30 non-SQ; median age 66 years [range 31-83]; 64% male; 96% current/prior smokers; ECOG 0/1: 37%/63%) received a median of 8 doses (range 1-27). Drug-related AEs were reported in 51% of patients; most frequent were fatigue (15%), diarrhea (12%), and decreased appetite (10%). Grade ≥ 3 drug-related AEs were reported in 9% of patients. Drug-related AEs led to discontinuation in 4 patients (7%); most frequent was diarrhea (2 patients). Fifty-two patients (23 SQ; 29 non-SQ) were evaluable for response with ≥ 12 weeks of follow-up. ORR (confirmed CR and PR) was 25% (11/43 PD-L1+; 1/8 PD-L1-), and disease control rate at ≥ 12 weeks was 56% (24/43 PD-L1+; 4/8 PD-L1-). ORR was similar for SQ (26%) and non-SQ (24%). Responses are ongoing in 9/13 responding patients (duration of response range: 5.7+ to 70.1+ weeks). Conclusions: Durvalumab monotherapy has a manageable safety profile with early evidence of clinical benefit in treatment-naïve SQ or non-SQ advanced NSCLC. A development program of durvalumab alone and in combination is ongoing in advanced NSCLC. Clinical trial information: NCT01693562.
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