title: A Phase II Efficacy and Safety, Open-Label, Multicenter Study of Imprime PGG Injection in Combination With Cetuximab in Patients With Stage IV KRAS-Mutant Colorectal Cancer.
abstract: Imprime PGG (β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose) is an innate immune cell modulator that primes neutrophils and monocytes/macrophages to exert antitumor activity against complement opsonized tumor cells. In patients with KRAS-mutant colorectal cancer (CRC), cetuximab alone is ineffective; however, it can bind to tumor cells and induce opsonization for recognition by Imprime PGG-bound innate immune cells. The primary objective of this study was to determine the antitumor activity of Imprime PGG in combination with cetuximab in patients with KRAS-mutant metastatic CRC.
  
  
  
  The study had a 2-stage Simon optimal design with 80% power to detect a target objective response rate (ORR) of ≥10% at a 10% significance level. Patients received weekly Imprime PGG (4 mg/kg) and cetuximab (loading dose, 400 mg/m(2), then 250 mg/m(2)) intravenously. The primary end point was ORR; secondary end points included duration of response (DOR), time to progression (TTP), overall survival (OS), disease control rate, progression-free survival, and safety. Stage 1 of the study was to enroll 17 evaluable patients.
  
  
  
  One partial response (5.6%) was observed among 18 patients enrolled into stage 1. Median DOR was 4.2 months, TTP 2.7 months, and OS 6.6 months. Overall, observed toxicity was as expected from cetuximab alone. The most common (≥20%) adverse events related to Imprime PGG were fatigue (7 patients; 38.9%), infusion reaction (4 patients; 22.2%), and headache (4 patients; 22.2%). There was no Grade 4 toxicity nor treatment-related deaths.
  
  
  
  Imprime PGG in combination with cetuximab treatment in patients with KRAS-mutant CRC showed compelling, albeit modest, clinical activity. This study provides proof of principle that Imprime PGG, in combination with complement-activating antibodies, is associated with clinical activity.
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: segaln@mskcc.org.
authors.forename: Neil H
authors.initials: NH
authors.lastname: Segal
authors.affiliation: University of Minnesota, Minneapolis, MN.
authors.forename: Purvi
authors.initials: P
authors.lastname: Gada
authors.affiliation: Mary Crowley Cancer Research Center, Dallas, TX.
authors.forename: Neil
authors.initials: N
authors.lastname: Senzer
authors.affiliation: Biothera, Eagan, MN.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Gargano
authors.affiliation: Biothera, Eagan, MN.
authors.forename: Myra L
authors.initials: ML
authors.lastname: Patchen
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Saltz
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068818:Cetuximab / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005936:Glucans / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D005936:Glucans; C117307:KRAS protein, human; C033671:epiglucan; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab
keywords: Antibody; Complement; Epidermal growth factor receptor; Immune; β-glucan