BTH1677 in combination with cetuximab with and without irinotecan in patients with advanced metastatic colorectal cancer

Cornelio, Gerardo H.; Tamayo, María; Flores, M. L.; Bautista, J. B.; Tioleco, P. S.; Gargano, M.; Kurman, Michael R.; Walsh, Richard; Béliveau, Martin; Marier, Jean-Francois; Patchen, Myra L.

doi:10.2217/crc-2016-0010

Cited by 4 publications

(6 citation statements)

References 28 publications

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“…Fatal AEs reported in the BTH1677 arm were generally associated with progression of disease. Overall, these safety findings further support a safety profile for BTH1677, which is consistent with our previous reports with BTH1677 alone [ 38 ] or in combination with MAb and chemotherapy in patients with metastatic colorectal cancer [ 39 ] and advanced NSCLC [ 40 ].…”

Section: Discussionsupporting

confidence: 90%

“…Pharmacokinetic (PK) parameters were proportional with dose [ 38 ]. Additionally, BTH1677 in combination with cetuximab, with or without irinotecan, was well tolerated with promising signs of efficacy in a phase Ib/II study in patients with recurrent or progressive metastatic colorectal cancer [ 39 ]. We also recently reported that BTH1677 combined with cetuximab/carboplatin/paclitaxel significantly improved ORR compared with cetuximab/carboplatin/paclitaxel in first-line treatment of patients with advanced NSCLC [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

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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

Engel-Riedel¹,

Lowe²,

Mattson³

et al. 2018

j. immunotherapy cancer

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BackgroundBTH1677, 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).MethodsPatients 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/m2, 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.ResultsORR 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.ConclusionsImprovements in tumor assessments and survival were observed with BTH1677/bevacizumab/carboplatin/paclitaxel compared with control treatment in patients with advanced NSCLC.Trial registrationClinicalTrials.gov registration ID: NCT00874107. Registered 2 April 2009. First participant was enrolled on 29 September 2009.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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

Engel-Riedel¹,

Lowe²,

Mattson³

et al. 2018

j. immunotherapy cancer

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“…BTH1677 is a novel PAMP being developed for the treatment of cancer in combination with tumor-targeted antibodies, as well as anti-angiogenic and checkpoint inhibitor antibodies. A previous phase Ib/II study in second- to third-line mCRC patients evaluated BTH1677 combined with cetuximab and showed good tolerability with promising efficacy [ 34 – 37 ]. This randomized, open-label, phase II study demonstrated that BTH1677 in combination with cetuximab, carboplatin, and paclitaxel numerically improved the ORR in patients with previously untreated, advanced NSCLC by 13% ( p = 0.2895; central review) to 24% ( p = 0.0468; investigator review) beyond the ORR observed in Control patients.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, BTH1677 in combination with cetuximab, with or without irinotecan, was well tolerated with promising evidence of efficacy in a phase Ib/II study in patients with recurrent or progressive metastatic colorectal cancer (mCRC) [35–37]. …”

Section: Introductionmentioning

confidence: 99%

“…Clinically, in healthy subjects, BTH1677 was well tolerated after single doses up to 6 mg/kg and after 7 daily doses up to 4 mg/kg and pharmacokinetic (PK) parameters demonstrated linearity with dose [ 34 ]. Additionally, BTH1677 in combination with cetuximab, with or without irinotecan, was well tolerated with promising evidence of efficacy in a phase Ib/II study in patients with recurrent or progressive metastatic colorectal cancer (mCRC) [ 35 – 37 ].…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2017

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Summary 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/m2 and subsequent doses 250 mg/m2, weekly; carboplatin, 6 mg/mL/min AUC (area-under-the-curve) by Calvert formula, once each 3-week cycle [Q3W]); and paclitaxel, 200 mg/m2, 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

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Tile-based self-assembly of a triple-helical polysaccharide into cell wall-like mesoporous nanocapsules

Wang

et al. 2017

Nanoscale

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Tile-based self-assembly is a robust system in the construction of three-dimensional DNA nanostructures but it has been rarely applied to other helical biopolymers. β-Glucan is an immunoactive natural polymer which exists in a triple helical conformation. Herein, we report that β-glucan, after modification using two types of short chain acyl groups, can self-assemble into tiles with inactivated sticky ends at the interface of two solvents. These tiles consist of a single layer of helices laterally aligned, and the sticky ends can be activated when a few acyl groups at the ends are removed; these tiles can further pack into mesoporous nanocapsules, in a similar process as the sticky DNA tiles pack into complex polyhedral nano-objects. These nanocapsules were found to have targeted effects to antigen presenting cells in a RAW264.7 cell model. Our study suggests that tile-based self-assembly can be a general strategy for helical biopolymers, and on fully exploiting this strategy, various new functional nanostructures will become accessible in the future.

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BTH1677 in combination with cetuximab with and without irinotecan in patients with advanced metastatic colorectal cancer

Cited by 4 publications

References 28 publications

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

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

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

Tile-based self-assembly of a triple-helical polysaccharide into cell wall-like mesoporous nanocapsules

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