Study of Imprime PGG® in Combination With Cetuximab in Subjects With Recurrent or Progressive KRAS Wild Type Colorectal Cancer

Study BT-CL-PGG-CRC1031 is a Phase 3, open-label, randomized, multi-center study. Qualified subjects, who have KRAS wild type (WT) colorectal cancer will be randomized in a 2:1 ratio to treatment with either Imprime PGG and cetuximab or cetuximab alone. Subjects will be dosed until progression or discontinuation for some other reason. Efficacy will be assessed via Response Evaluation Criteria in Early Tumors 1.1 (RECIST 1.1); computed tomography (CT) scans will be conducted every 6 weeks. Safety, pharmacokinetics (PK), quality of life, and biomarker parameters will also be assessed.

Study BT-CL-PGG-CRC1031 is a Phase 3, open-label, randomized, multi-center study. Qualified subjects, who have KRAS WT colorectal cancer will be randomized in a 2:1 ratio to either:

Arm 1: Imprime PGG and cetuximab or Arm 2: Cetuximab

Approximately 795 subjects will be randomized into the study. Dosing will occur in 6-week cycles. Imprime PGG will be dosed at 4 mg/kg and will be administered weekly in each cycle (Weeks 1-6/Days 1, 8, 15, 22, 29, and 36) preceding the administration of cetuximab (Arm 1 only). The initial cetuximab dose (both arms) will be 400 mg/m2 on Cycle 1/Day 1 and subsequent doses will be 250 mg/m2 administered weekly in each cycle (Weeks 1-6/Days 1, 8, 15, 22, 29, and 36).

Subjects will be dosed until progressive disease (PD) per RECIST 1.1 or discontinuation of study drug for other reasons; e.g., safety. Following completion of the treatment period of the study, subjects will be monitored for survival until death or loss to follow-up. Tumor measurements and determination of tumor responses will be evaluated according to RECIST 1.1. Safety, PK, quality of life, and biomarker parameters will also be assessed.

Eligibility Criteria:
Inclusion Criteria:

1. Is \>18 years old;
2. Has recurrent or metastatic carcinoma of the colon or rectum with documented histological or cytological confirmation;
3. Must be KRAS WT;
4. Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1;
5. Has never received cetuximab or panitumumab, and has not received any treatment for colorectal cancer within 30 days prior to the first dose of study treatment under this protocol;
6. Has an Eastern Cooperative Oncology Group (ECOG) score of 0-1, with a life expectancy of \>3 months;
7. Has received at least 2 prior chemotherapeutic regimens for colorectal cancer;
8. Has adequate bone marrow reserve as evidenced by:

   * Absolute neutrophil count ≥1,500/μL
   * Platelets ≥100,000/μL;
9. Has adequate renal function as evidenced by serum creatinine ≤2.5 × the upper limit of normal (ULN) for the reference lab;
10. Has adequate hepatic function as evidenced by:

    * Aspartate aminotransferase ≤3 × ULN for the reference lab (≤5 × ULN for subjects with known hepatic metastases)
    * Alanine aminotransferase ≤3 × ULN for the reference lab (≤5 × ULN for subjects with known hepatic metastases)
    * Bilirubin \<1.5 mg/dL or direct bilirubin \<1.0 mg/dL
    * Serum Albumin \>3.0 gm/dL
11. Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Independent Ethics Committee (IRB/IEC); and
12. If the subject is a woman of childbearing potential or a fertile man, he/she must agree to use an effective form of contraception during the study and for 60 days following the last dose of study drug (an effective form of contraception is abstinence, a hormonal contraceptive, or a double-barrier method).

Exclusion Criteria:

1. Has a known hypersensitivity to cetuximab, murine proteins, or any component of cetuximab;
2. Has a known hypersensitivity to baker's yeast or has an active yeast infection;
3. Has had previous exposure to Betafectin® or Imprime PGG;
4. Has an active, uncontrolled infection;
5. Has known untreated or symptomatic brain metastases;
6. Had a second malignancy within the previous 5 years, except for basal cell carcinoma, cervical intra-epithelial neoplasia or treated prostate cancer with a prostate-specific antigen (PSA) of \<2.0 ng/mL;
7. Has known human immunodeficiency virus or acquired immune deficiency syndrome, hepatitis B, hepatitis C, connective tissue disease, or other clinical diagnosis, ongoing or intercurrent illness that in the Investigators opinion should preclude the subject from participation;
8. If female, is pregnant or breast-feeding;
9. Is receiving concurrent standard and/or investigational anti-cancer therapy or has received such therapy within a period of 30 days prior to the first scheduled day of dosing (investigational therapy is defined as treatment for which there is currently no regulatory-authority-approved indication); or
10. Has previously received an organ or progenitor/stem cell transplant.