ALD518, a humanized anti-IL-6 antibody, treats anemia in patients with advanced non-small cell lung cancer (NSCLC): Results of a phase II, randomized, double-blind, placebo-controlled trial.

Abstract

7631 Background: ALD518 is a humanized anti-IL-6 antibody being developed for the treatment of cancer- related anemia, cachexia, and fatigue. The primary objective of the study was to determine the efficacy and safety of ALD518 in patients with advanced NSCLC. Methods: 124 patients (pts) with NSCLC, ECOG 0-3, weight loss in the preceding 3 months of >5% body weight, hemoglobin (Hb) >7 g/dL, and C-reactive protein (CRP) >10 mg/L were dosed. Pts were randomized to 1 of 4 groups (n∼30/group). Placebo or ALD518 80 mg, 160 mg, or 320 mg was administered intravenously every 8 weeks. Pts were followed up for 24 weeks. Data included hematology, clinical chemistry, CRP, and adverse events (AEs). Results: 29 pts completed the study treatments and evaluations, 38 failed to complete every visit, 52 died of progressive disease, and 5 withdrew because of adverse events. There were no dose-limiting toxicities (DLTs) or infusion reactions. 84 pts had serious AEs of which 1 was deemed to be possibly related to administration of ALD518 (rectal hemorrhage). The mean (±SD) values for Hb, hematocrit (Hct), mean corpuscular Hb (MCH), and albumin are shown in the Table. 38/93 pts treated with ALD518 and 10/31 given placebo had a pre-dose Hb =<11 g/dL. 24 of these pts on ALD518 and 7 of these pts on placebo remained in the study at week 4. 14/24 pts on ALD518 and 0/7 on placebo had raised their Hb from =<11 g/dL to >=12 g/dL. Conclusions: ALD518 increased Hb, Hct, MCH and albumin in NSCLC pts and raised Hb to >=12g/dL in 58% of pts with a Hb =<11 g/dL at baseline. ALD518 may be a novel non-erythropoietic stimulating agent for cancer-related anemia. There were no major safety signals related to the administration of ALD518. n Hb (g/dL) Hct (%) MCH (pg) Albumin (g/L) ALD518 Pre-dose 93 11.5 (±2.1) 37.9 (±6.2) 28.4 (±2.8) 37.3 (±5.3) (pooled) Week 4 69 13.1 (±1.6)a 42.5 (±5.0)a 29.2 (±2.5)a 43.6 (±4.7)a Week 12 39 13.4 (±1.6)a 42.5 (±4.7)b 29.8 (±2.8)a 45.2 (±4.5)a Placebo Pre-dose 31 12.2 (±1.8) 39.0 (±5.9) 29.0 (±2.8) 37.5 (±5.7) Week 4 29 11.8 (±2.0) 39.5 (±6.4) 28.0 (±2.8)c 37.3 (±6.8) Week 12 21 12.0 (±2.5) 39.6 (±7.4) 27.8 (±3.0)c 37.0 (±7.5) a p < 0.0001; b p = 0.0002; c p ≤ 0.001 (paired t-test compared to pre-dose). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Alder Biopharmaceuticals Inc. Alder Biopharmaceuticals Inc. Alder Biopharmaceuticals Inc.