A randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of BTH1677 (1,3–1,6 beta glucan; Imprime PGG) in combination with cetuximab and chemotherapy in patients with advanced non-small cell lung cancer

• DOI: 10.1007/s10637-017-0450-3
• Publication Date: 2017-03-16T06:55:23Z
• Authors: M. Thomas; P. Sadjadian; J. Kollmeier; J. Lowe; P. Mattson; J. R. Trout; M. Gargano; M. L. Patchen; R. Walsh; M. Beliveau; J. F. Marier; N. Bose; K. Gorden; F. Schneller
• Keywords: Carboplatin; Clinical endpoint

Summary Introduction BTH1677, a 1,3–1,6 beta-glucan immunomodulator, stimulates coordinated anti-cancer immune response in combination with anti-tumor antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined cetuximab/carboplatin/paclitaxel untreated stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods Patients were randomized 2:1 to arm ( N =60; 4 mg/kg, weekly; cetuximab, initial dose 400 mg/m 2 subsequent doses 250 , carboplatin, 6 mg/mL/min AUC (area-under-the-curve) by Calvert formula, once each 3-week cycle [Q3W]); paclitaxel, 200 Q3W) or Control =30; as above). Carboplatin/paclitaxel was discontinued after 4–6 cycles; patients who responded remained stable received maintenance therapy BTH1677/cetuximab (BTH1677 arm) cetuximab (Control arm). Investigator blinded central radiology reviews conducted. Efficacy assessments included objective rate (ORR; primary endpoint), disease control rate, duration response, time-to-progression overall survival (OS); assessed adverse events (AEs). Potential biomarker analysis for also Results Compared treatment, addition numerically increased ORR both investigator (47.8% vs 23.1%; p=0.0468) (36.6% p=0.2895) reviews. No other endpoints differed between arms. PK consistent previous studies. well tolerated, AEs expected backbone predominating. Biomarker-positive displayed better OS than negative Conclusions tolerated improved first-line treatment advanced NSCLC. Future patient selection status may further improve efficacy ClinicalTrials.gov Identifier: NCT00874848