PMID- 29486797 OWN - NLM STAT- MEDLINE DCOM- 20191015 LR - 20191015 IS - 2051-1426 (Electronic) IS - 2051-1426 (Linking) VI - 6 IP - 1 DP - 2018 Feb 27 TI - A randomized, controlled trial evaluating the efficacy and safety of BTH1677 in combination with bevacizumab, carboplatin, and paclitaxel in first-line treatment of advanced non-small cell lung cancer. PG - 16 LID - 10.1186/s40425-018-0324-z [doi] LID - 16 AB - BACKGROUND: BTH1677, a beta-glucan pathogen-associated molecular pattern molecule, drives an anti-cancer immune response in combination with oncology antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with bevacizumab/carboplatin/paclitaxel in patients with untreated advanced non-small cell lung cancer (NSCLC). METHODS: Patients were randomized to the BTH1677 arm (N = 61; intravenous [IV] BTH1677, 4 mg/kg, weekly; IV bevacizumab, 15 mg/kg, once each 3-week cycle [Q3W]; IV carboplatin, 6 mg/mL/min Calvert formula area-under-the-curve, Q3W; and IV paclitaxel, 200 mg/m(2), Q3W) or Control arm (N = 31; bevacizumab/carboplatin/paclitaxel as above). Carboplatin/paclitaxel was discontinued after 4-6 cycles and patients who responded or remained stable received maintenance therapy with BTH1677/bevacizumab (BTH1677 arm) or bevacizumab (Control arm). Efficacy assessments, based on blinded central radiology review, included objective response rate (ORR; primary endpoint), disease control rate, duration of objective response, and progression-free survival. Overall survival and adverse events (AEs) were also assessed. RESULTS: ORR was higher in the BTH1677 vs Control arm but the difference between groups was not statistically significant (60.4% vs 43.5%; P = .2096). All other clinical endpoints also favored the BTH1677 arm but none statistically differed between arms. PK was consistent with previous studies. Although a higher incidence of Grade 3/4 AEs occurred in the BTH1677 vs Control arm (93.2% vs 66.7%), no unexpected AEs were observed. Serious AEs and discontinuations due to AEs were lower in the BTH1677 vs Control arm. CONCLUSIONS: Improvements in tumor assessments and survival were observed with BTH1677/bevacizumab/carboplatin/paclitaxel compared with control treatment in patients with advanced NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov registration ID: NCT00874107 . Registered 2 April 2009. First participant was enrolled on 29 September 2009. FAU - Engel-Riedel, Walburga AU - Engel-Riedel W AD - Kliniken der Stadt Koln gGmbH, Krankenhaus Merheim, Thoraxchirurgische u. Pneumologische Klinik, Ostmerheimer Str. 200, 51109, Koln, Germany. FAU - Lowe, Jamie AU - Lowe J AD - Biothera Pharmaceuticals, Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 55121, USA. FAU - Mattson, Paulette AU - Mattson P AD - Biothera Pharmaceuticals, Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 55121, USA. FAU - Richard Trout, J AU - Richard Trout J AD - Rutgers University, 82 Rittenhouse Circle, Newtown, PA, 18940, USA. FAU - Huhn, Richard D AU - Huhn RD AD - Biothera Pharmaceuticals, Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 55121, USA. FAU - Gargano, Michele AU - Gargano M AD - Biothera Pharmaceuticals, Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 55121, USA. FAU - Patchen, Myra L AU - Patchen ML AD - Biothera Pharmaceuticals, Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 55121, USA. mpatchen@immunoresearch.com. AD - PresentAddress: Immuno Research, Inc., 3388 Mike Collins Drive, Suite B, Eagan, MN, 55121, USA. mpatchen@immunoresearch.com. FAU - Walsh, Richard AU - Walsh R AD - Biothera Pharmaceuticals, Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 55121, USA. FAU - Trinh, My My AU - Trinh MM AD - Certara Strategic Consulting, 2000 Peel Street, Suite 570, Montreal, Quebec, H3A2WS, Canada. FAU - Dupuis, Marieve AU - Dupuis M AD - Certara Strategic Consulting, 2000 Peel Street, Suite 570, Montreal, Quebec, H3A2WS, Canada. FAU - Schneller, Folker AU - Schneller F AD - Medical Clinic and Polyclinic of Klinikum rechts der Isar of Technical University Munich, Ismaninger Str. 22, 81675, Munich, Germany. LA - eng SI - ClinicalTrials.gov/NCT00874107 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180227 PL - England TA - J Immunother Cancer JT - Journal for immunotherapy of cancer JID - 101620585 RN - 0 (BTH1677) RN - 0 (Glucans) RN - 2S9ZZM9Q9V (Bevacizumab) RN - BG3F62OND5 (Carboplatin) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects/pharmacokinetics MH - Bevacizumab/*administration & dosage/adverse effects MH - Carboplatin/*administration & dosage/adverse effects MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Female MH - Glucans/*administration & dosage/adverse effects/pharmacokinetics MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Paclitaxel/*administration & dosage/adverse effects MH - Treatment Outcome PMC - PMC5830087 OTO - NOTNLM OT - Beta-glucan OT - Bevacizumab OT - Immunotherapy OT - NSCLC COIS- AUTHORS' INFORMATION: Not applicable. ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Prior to enrollment, all study materials were approved by the governing ethics committee, Technical University Munich, Faculty for Medicine, Ethics Committee, Ismaninger Str. 22, 81,675 Munich, Germany (Project No. 2292/08; EudraCT No. 2008-006780-37) or institutional review boards (Schulman Associates IRB, Inc., 4445 Lake Forest Drive, Suite 300, Cincinnati, OH 45242 USA; Compass Independent Review Board, LLC, 5416 East Baseline Rd., Suite 120, Mesa, AZ 85206 USA; Mary Crowley Medical Research Center, Institutional Review Board, 1700 Pacific Avenue, Suite 1100, Dallas, TX 75201 USA [no patients were enrolled]; UT Health Science Center San Antonio, Institutional Review Board, Mail Code 7830, 7703 Floyd Curl Drive, San Antonio, TX 78229 USA; Brooke Army Medical Center Institutional Review Board, 3551 Roger Brooke Dr., Fort Sam Houston, TX 78234 USA [no patients were enrolled]) at each site. This study was conducted in full accordance with the Good Clinical Practice: Consolidated Guideline approved by the International Conference on Harmonisation and all other applicable national and local laws/regulations. Adult patients who had given written informed consent were eligible to participate in the study. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: WE-R has received honoraria from Eli Lilly and Company, Boehringer-Ingelheim, Roche, BMS, and Merck. At the time this study was performed, JL, PM, RDH, MG, MLP, and RW were employed in leadership roles at Biothera Pharmaceuticals Inc. and owned stock/stock options in Biothera Pharmaceuticals Inc. MMT and MD were compensated by Biothera for pharmacokinetic and data analysis assistance. JRT was compensated by Biothera for statistical analysis assistance. FS has no conflicts of interest to disclose. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/03/01 06:00 MHDA- 2019/10/16 06:00 PMCR- 2018/02/27 CRDT- 2018/03/01 06:00 PHST- 2017/10/19 00:00 [received] PHST- 2018/02/13 00:00 [accepted] PHST- 2018/03/01 06:00 [entrez] PHST- 2018/03/01 06:00 [pubmed] PHST- 2019/10/16 06:00 [medline] PHST- 2018/02/27 00:00 [pmc-release] AID - 10.1186/s40425-018-0324-z [pii] AID - 324 [pii] AID - 10.1186/s40425-018-0324-z [doi] PST - epublish SO - J Immunother Cancer. 2018 Feb 27;6(1):16. doi: 10.1186/s40425-018-0324-z.