Avelumab (MSB0010718C; anti-PD-L1) as a first-line treatment for patients with advanced NSCLC from the JAVELIN Solid Tumor phase 1b trial: Safety, clinical activity, and PD-L1 expression.
2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2016.34.15_suppl.9036
ISSN1527-7755
AutoresClaire F. Verschraegen, Franklin Chen, David R. Spigel, Nicholas Iannotti, Edward F. McClay, Charles Redfern, Jaafar Bennouna, Matthew H. Taylor, Howard L. Kaufman, Karen Kelly, Marcis Bajars, Anja von Heydebreck, Jean-Marie Cuillerot, Guy Jérusalem,
Tópico(s)Cancer Immunotherapy and Biomarkers
Resumo9036 Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of avelumab as 1st-line therapy in patients (pts) with non-small-cell lung cancer (NSCLC) from a phase 1b trial (NCT01772004). Methods: Pts with advanced NSCLC not previously treated systemically for metastatic or recurrent disease, without an activating EGFR mutation or ALK rearrangement, and not selected for PD-L1 expression were treated with avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Responses were evaluated every 6 wks (RECIST 1.1). Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by IHC. Results: As of Oct 23, 2015, 145 pts received avelumab (median 10 wks [range 2-30]) and were followed for a median duration of 13 wks (range 0-31). Median age was 70 y (range 41-90), ECOG PS was 0 (31.0%) or 1 (69.0%), and histology was adenocarcinoma (63.4%), squamous (26.9%), other (3.4%), or unknown (6.2%). Treatment-related (TR) AEs occurred in 82 pts (56.6%; all grades); those occurring ≥ 10% were infusion-related reaction (IRR; 24 [16.6%]) and fatigue (21 [14.5%]). Grade ≥ 3 TRAEs were reported in 13 pts (9.0%); only IRR and fatigue occurred in > 1 pt (each 3 [2.1%]). There were no treatment-related deaths. Among 75 pts with ≥ 3 mos f/u, unconfirmed ORR was 18.7% (95% CI: 10.6, 29.3) based on 1 CR and 13 PRs; 12 were ongoing. Stable disease was reported in 34 pts (45.3%); disease control rate was 64.0%. PD-L1 expression was evaluable in 45/75 pts (60.0%). Based on a ≥ 1% cutoff for tumor cell staining, 35/45 (77.8%) were PD-L1+ and ORR was 20.0% in PD-L1+ (7/35; 95% CI: 8.4, 36.9) vs 0/10 (0.0, 30.8) in PD-L1– pts. Median PFS was 11.6 wks (95% CI: 6.7, 17.9) for all treated pts. Conclusions: Single-agent avelumab showed an acceptable safety profile and clinical activity in pts with NSCLC who were EGFR-wildtype and ALK-negative, not previously treated for advanced disease, and unselected for PD-L1 expression. A trend of higher ORR in PD-L1+ tumors is suggested. Phase 3 trials of avelumab in NSCLC are ongoing. *Proposed INN. Clinical trial information: NCT01772004.
Referência(s)