PMID- 28303530
OWN - NLM
STAT- MEDLINE
DCOM- 20180321
LR  - 20200306
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 35
IP  - 3
DP  - 2017 Jun
TI  - 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.
PG  - 345-358
LID - 10.1007/s10637-017-0450-3 [doi]
AB  - Introduction BTH1677, a 1,3-1,6 beta-glucan immunomodulator, stimulates a 
      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 with cetuximab/carboplatin/paclitaxel in untreated 
      stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods Patients were 
      randomized 2:1 to the BTH1677 arm (N=60; BTH1677, 4 mg/kg, weekly; cetuximab, 
      initial dose 400 mg/m(2) and subsequent doses 250 mg/m(2), weekly; carboplatin, 6 
      mg/mL/min AUC (area-under-the-curve) by Calvert formula, once each 3-week cycle 
      [Q3W]); and paclitaxel, 200 mg/m(2), Q3W) or Control arm (N=30; 
      cetuximab/carboplatin/paclitaxel as above). Carboplatin/paclitaxel was 
      discontinued after 4-6 cycles; patients who responded or remained stable received 
      maintenance therapy with BTH1677/cetuximab (BTH1677 arm) or cetuximab (Control 
      arm). Investigator and blinded central radiology reviews were conducted. Efficacy 
      assessments included objective response rate (ORR; primary endpoint), disease 
      control rate, duration of objective response, time-to-progression and overall 
      survival (OS); safety was assessed by adverse events (AEs). Potential biomarker 
      analysis for BTH1677 response was also conducted. Results Compared to control 
      treatment, the addition of BTH1677 numerically increased ORR by both investigator 
      (47.8% vs 23.1%; p=0.0468) and central (36.6% vs 23.1%; p=0.2895) reviews. No 
      other endpoints differed between arms. PK was consistent with previous studies. 
      BTH1677 was well tolerated, with AEs expected of the backbone therapy 
      predominating. Biomarker-positive patients displayed better ORR and OS than 
      negative patients. Conclusions BTH1677 combined with 
      cetuximab/carboplatin/paclitaxel was well tolerated and improved ORR as 
      first-line treatment in patients with advanced NSCLC. Future patient selection by 
      biomarker status may further improve efficacy ClinicalTrials.gov Identifier: 
      NCT00874848.
FAU - Thomas, M
AU  - Thomas M
AD  - Internistische Onkologie der Thoraxtumoren, Thoraxklinik im Universitatsklinikum 
      Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the 
      German Center for Lung Research (DZL), Amalienstrasse 5, 69126, Heidelberg, 
      Germany.
FAU - Sadjadian, P
AU  - Sadjadian P
AD  - Johannes Wesling Medical Center Minden, Clinic Hematology/Oncology, 
      Hans-Nolte-Str. 1, 32429, Minden, Germany.
FAU - Kollmeier, J
AU  - Kollmeier J
AD  - Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Specialist Department 
      1: Clinic for Pneumology, Pneumology Oncology, Walterhoferstr.11, 14165, Berlin, 
      Germany.
FAU - Lowe, J
AU  - Lowe J
AD  - Biothera Pharmaceuticals Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 
      55121, USA.
FAU - Mattson, P
AU  - Mattson P
AD  - Biothera Pharmaceuticals Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 
      55121, USA.
FAU - Trout, J R
AU  - Trout JR
AD  - Rutgers University, 82 Rittenhouse Circle, Newtown, PA, 18940, USA.
FAU - Gargano, M
AU  - Gargano M
AD  - Biothera Pharmaceuticals Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 
      55121, USA.
FAU - Patchen, M L
AU  - Patchen ML
AD  - Biothera Pharmaceuticals Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 
      55121, USA. mpatchen@immunoresearch.com.
AD  - Immuno Research, Inc., 3388 Mike Collins Drive, Suite B, Eagan, MN, 55121, USA. 
      mpatchen@immunoresearch.com.
FAU - Walsh, R
AU  - Walsh R
AD  - Biothera Pharmaceuticals Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 
      55121, USA.
FAU - Beliveau, M
AU  - Beliveau M
AD  - Pharsight/Certara, Pharsight - A Certara Company, 2000 Peel Street, Suite 570, 
      Montreal, Quebec, H3A 2W5, Canada.
FAU - Marier, J F
AU  - Marier JF
AD  - Pharsight/Certara, Pharsight - A Certara Company, 2000 Peel Street, Suite 570, 
      Montreal, Quebec, H3A 2W5, Canada.
FAU - Bose, N
AU  - Bose N
AD  - Biothera Pharmaceuticals Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 
      55121, USA.
FAU - Gorden, K
AU  - Gorden K
AD  - Biothera Pharmaceuticals Inc., 3388 Mike Collins Drive, Suite A, Eagan, MN, 
      55121, USA.
FAU - Schneller, F 3rd
AU  - Schneller F 3rd
AD  - Medical Clinic and Polyclinic, Klinikum rechts der Isar of Technical University 
      Munich, Ismaninger Str. 22, 81675, Munich, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT00874848
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170316
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antineoplastic Agents)
RN  - 0 (BTH1677)
RN  - 0 (Glucans)
RN  - BG3F62OND5 (Carboplatin)
RN  - P88XT4IS4D (Paclitaxel)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/adverse effects/blood/pharmacokinetics/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Carboplatin/adverse effects/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism
MH  - Cetuximab/adverse effects/*therapeutic use
MH  - Female
MH  - Glucans/adverse effects/blood/pharmacokinetics/*therapeutic use
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*drug therapy/metabolism
MH  - Male
MH  - Middle Aged
MH  - Paclitaxel/adverse effects/*therapeutic use
MH  - Treatment Outcome
PMC - PMC5418307
OTO - NOTNLM
OT  - Beta glucan
OT  - Biomarker
OT  - Cetuximab
OT  - Immunotherapy
OT  - NSCLC
COIS- CONFLICT OF INTEREST: At the time this study was performed, Nandita Bose, Michele 
      Gargano, Keith Gorden, Jamie Lowe, Paulette Mattson, Myra Patchen, and Richard 
      Walsh were employed in leadership roles at Biothera Pharmaceuticals Inc. and 
      owned stock/stock options in Biothera Pharmaceuticals Inc. Martin Beliveau and JF 
      Marier were compensated by Biothera for pharmacokinetic analysis assistance and J 
      Richard Trout was compensated by Biothera for statistical analysis assistance. 
      The remaining authors declare no conflict of interest. FUNDING: This work was 
      supported by Biothera Pharmaceuticals Inc. ETHICAL APPROVAL: This Phase II 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. All study materials were approved 
      by the governing ethics committee or institutional review board at each site. 
      INFORMED CONSENT: Informed consent was obtained from all individual patients 
      included in the study.
EDAT- 2017/03/18 06:00
MHDA- 2018/03/22 06:00
PMCR- 2017/03/16
CRDT- 2017/03/18 06:00
PHST- 2017/02/16 00:00 [received]
PHST- 2017/03/01 00:00 [accepted]
PHST- 2017/03/18 06:00 [pubmed]
PHST- 2018/03/22 06:00 [medline]
PHST- 2017/03/18 06:00 [entrez]
PHST- 2017/03/16 00:00 [pmc-release]
AID - 10.1007/s10637-017-0450-3 [pii]
AID - 450 [pii]
AID - 10.1007/s10637-017-0450-3 [doi]
PST - ppublish
SO  - Invest New Drugs. 2017 Jun;35(3):345-358. doi: 10.1007/s10637-017-0450-3. Epub 
      2017 Mar 16.