A phase III, randomized, double-blind, multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer

Objectives: Efficacy, safety, pharmacokinetics (PK), and immunogenicity of the biosimilar candidate SB8 was compared to its reference product bevacizumab (BEV) in patients with metastatic or recurrent nonsquamous non―small cell lung cancer. Methods: Patients were randomized (1:1) in a phase III, double-blind study to receive intravenous SB8 or BEV 15 mg/kg with paclitaxel/carboplatin every 3 weeks for 24 weeks, followed by SB8 or BEV maintenance monotherapy. The primary endpoint was best overall response rate (ORR) by 24 weeks. Secondary endpoints included survival outcomes, safety, PK, and immunogenicity. Results: 763 patients (SB8, n = 379; BEV, n = 384) were randomized; baseline characteristics were well balanced. Best ORR in the FAS was 47.6% and 42.8%, and best ORR in the PPS was 50.1% and 44.8% for SB8 and BEV, respectively. The risk ratio of best ORR was 1.11 (90% CI, 0.975−1.269), and the risk difference in best ORR was 5.3% (95% CI, −2.2%–12.9%). Median survival outcomes were comparable between SB8 and BEV: progression-free survival was 8.50 vs 7.90 months, respectively (HR [95% CI], 0.99 [0.83–1.18]; p = 0.9338); overall survival was 14.90 vs 15.80 months, respectively (HR [95% CI], 1.03 [0.83–1.28]; p = 0.7713); and duration of response was 7.70 vs 7.00 months, respectively (HR [95% CI], 1.05 [0.81–1.37]; p = 0.6928). Severity and incidence of treatment-emergent adverse events, PK, and immunogenicity were comparable between SB8 and BEV. Conclusion: This study demonstrated equivalence between SB8 and BEV in terms of best ORR risk ratio, with comparable safety, PK, and immunogenicity

Caspian: Os Results from a Randomised Phase 3 Study of First-Line Durvalumab ± Tremelimumab + Chemotherapy in ES-SCLC

Immune checkpoint blockade targeting the PD-1/PD-L1 pathway in combination with platinum-based chemotherapy (CT) has demonstrated improved clinical outcomes in patients (pts) with extensive-stage small-cell lung cancer (ES-SCLC). Durvalumab ± Tremelimumab in combination with etoposide and platinum-based CT (EP) as first-line treatment for pts with ES-SCLC. Results will be presented at WCLC 2019 including OS, key secondary endpoints, safety and tolerability

Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study

Objectives In the phase III CASPIAN study, first-line durvalumab plus etoposide in combination with either cisplatin or carboplatin (EP) significantly improved overall survival (primary endpoint) versus EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) at the interim analysis. Here we report patient-reported outcomes (PROs). Materials and methods Treatment-naïve patients with ES-SCLC received 4 cycles of durvalumab plus EP every 3 weeks followed by maintenance durvalumab every 4 weeks until progression, or up to 6 cycles of EP every 3 weeks. PROs, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), were prespecified secondary endpoints. Changes from baseline to disease progression or 12 months in prespecified key disease-related symptoms (cough, dyspnea, chest pain, fatigue, appetite loss) were analyzed with a mixed model for repeated measures. Time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization was analyzed. Results In the durvalumab plus EP and EP arms, 261 and 260 patients were PRO-evaluable. Patients in both arms experienced numerically reduced symptom burden over 12 months or until progression for key symptoms. For the improvements from baseline in appetite loss, the between-arm difference was statistically significant, favoring durvalumab plus EP (difference, −4.5; 99% CI: −9.04, −0.04; nominal p = 0.009). Patients experienced longer TTD with durvalumab plus EP versus EP for all symptoms (hazard ratio [95% CI] for key symptoms: cough 0.78 [0.600‒1.026]; dyspnea 0.79 [0.625‒1.006]; chest pain 0.76 [0.575‒0.996]; fatigue 0.82 [0.653‒1.027]; appetite loss 0.70 [0.542‒0.899]), functioning, and global health status/QoL. Conclusion Addition of durvalumab to first-line EP maintained QoL and delayed worsening of patient-reported symptoms, functioning, and global health status/QoL compared with EP

Effect of Amplitude on the Surface Dilational Visco-Elasticity of Protein Solutions

Harmonic drop surface area oscillations are performed at a fixed frequency (0.1 Hz) to measure the dilational visco-elasticity for three proteins: β-casein (BCS), β-lactoglobulin (BLG), and human serum albumin (HSA). The surface area oscillations were performed with different amplitudes in order to find the origin of non-linearity effects. The analysis of data shows that the non-linearity in the equation of state—i.e., the relation between surface pressure and surface concentration of adsorbed protein molecules—is the main source of the amplitude effects on the apparent visco-elasticity, while perturbations due to non-uniform expansions and compressions of the surface layer, inertia effects leading to deviations of the drop profile from the Laplacian shape, or convective transport in the drop bulk are of less importance. While for the globular proteins, HSA and BLG the amplitude effects on the apparent visco-elasticity are rather large, for the non-globular protein BCS this effect is negligible in the studied range of up to 10% area deformation