Efect of ALD518, a humanized anti-IL-6 antibody, on lean body mass loss and symptoms in patients with advanced non-small cell lung cancer (NSCLC): Results of a phase II randomized, double-blind safety and efficacy trial.

Abstract

7622 Background: ALD518 is a humanized anti-IL-6 antibody being developed for the treatment of anemia, cachexia, and fatigue. The primary objective of the study was to determine the efficacy and safety of ALD518. Methods: 124 patients (pts) with advanced NSCLC, ECOG 0-3, weight loss in the preceding 3 months of >5% body weight, hemoglobin >7g/dl and C-reactive protein (CRP) > 10 mg/L were dosed. Pts were randomized to 1 of 4 treatment groups (∼30/group). Placebo or ALD518 80 mg, 160 mg, or 320 mg was administered i.v. every 8 weeks. Pts were followed up for 24 weeks. Data included FACIT-F, FACT-L, body composition (DEXA), lab safety tests (LSTs) and adverse events (AEs). Results: 29 pts completed the study, 52 died of progressive disease, 5 withdrew because of AEs, and 38 failed to complete every visit. There were no DLTs or infusion reactions. 84 pts had serious AEs of which 1 was deemed possibly related to administration of ALD518 (rectal hemorrhage). Enough patients remained in the study up to week 12 to make a statistical comparison valid. The mean (±SD) values for lean body mass (LBM), FACT-L lung symptom subscale (LCS) and FACIT-F fatigue subscale (FS) are shown in the Table. Conclusions: ALD518 given to pts with NSCLC was safe and well tolerated. ALD518 improved the lung symptom score, reversed fatigue, and there was less loss of LBM (-0.19 kg on ALD518 vs. -1.50 kg on placebo). There were no major safety signals or infusion reactions related to the administration of ALD518. Visit n LBM (kg) n FACT-LLCS n FACIT-FFS ALD518 Pre-dose 93 41.90 (±9.35) 93 13.3 (±4.3) 93 20.5 (±9.6) (pooled) Week 2 - - 79 15.1 (±3.8)* 79 22.9 (±10.5)** Week 12 35 41.71 (±10.29) 39 15.6 (±5.2) 39 23.8 (±10.9) Placebo Pre-dose 31 41.58 (±10.74) 31 13.7 (±3.4) 31 21.9 (±9.6) Week 2 - - 29 14.1 (±4.2) 29 21.3 (±11.1) Week 12 20 40.08 (±11.00) 21 15.2 (±3.9) 21 22.1 (±13.2) * p ≤ 0.0006. ** p = 0.025 (paired t-test compared to baseline). 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.