Phase I, Multicenter, Dose Escalation Study of DCR-MYC in Patients With Solid Tumors, Multiple Myeloma, or Lymphoma

Inclusion Criteria:

   1. Male or female patients, > 18 years of age at the time of obtaining informed consent.

   2. Patients with a documented solid tumor malignancy that is locally advanced or
   metastatic; patients with documented multiple myeloma or non-Hodgkin's lymphoma.

   3. Patients with a malignancy that is either refractory to standard therapy or for which
   no standard therapy is available.

   4. Patients with a malignancy that is currently not amenable to surgical intervention due
   to either medical contraindications or non-resectability of the tumor.

   5. Dose escalation portion of study: Patients with measurable or non-measurable disease
   according to standard response criteria .

   6. MTD Biopsy Cohort ONLY: Patients with measurable disease with primary or metastatic
   tumor site(s) considered safely accessible for biopsy; patients must consent to
   undergo 2 tumor biopsies.

   7. MTD PNET Cohort ONLY: Patients with advanced (unresectable or metastatic),
   histologically-confirmed low or intermediate grade PNET according to the World Health
   Organization (WHO) 2010 classification. Patients with neuroendocrine tumors (e.g.,
   gastrinoma, VIPoma) in whom a pancreatic or peripancreatic primary is strongly
   suspected are also eligible. Patients must also have:

      - A Ki-67 proliferation index < 20%

      - Demonstrated radiological evidence of disease progression during or following the
      last treatment regimen (based on CT, MRI, or Octreoscan®)

      - Measurable disease according to RECIST v1.1 (determined by CT or MRI). Any
      lesions which have been subjected to percutaneous therapies or radiotherapy
      should not be considered measureable, unless the lesion has clearly progressed
      (per RECIST v1.1) since the procedure.

      - Received < 2 prior systemic treatments for PNET, at least one of which must have
      been an FDA-approved targeted therapy for PNET (i.e., sunitinib [Sutent®] or
      everolimus [Afinitor®]). Treatment with a somatostatin analog (SSA) will not be
      considered as a systemic treatment for the purposes of eligibility.

   8. Patients with an Eastern Cooperative Oncology Group performance status of 0, 1, or 2,
   and an anticipated life expectancy of ≥ 3 months.

   9. Patients, both male and female, who are either not of childbearing potential or who
   agree to use a medically effective method of contraception during the study and for 3
   months after the last dose of study drug.

10. Patients with the ability to understand and give written informed consent for
   participation in this trial, including all evaluations and procedures as specified by
   this protocol.

Exclusion Criteria-Patients:

   1. Women who are pregnant or lactating. Women of child-bearing potential (WOCBP), and
   fertile men with a WOCBP-partner not using and not willing to use a medically
   effective method of contraception.

   2. Patients with known central nervous system (CNS) or leptomeningeal metastases not
   controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS
   involvement for which treatment is required.

   3. Patients with leukemia (any form) or myelodysplastic syndromes.

   4. MTD PNET Cohort ONLY: Patients with poorly differentiated, high grade (grade 3)
   neuroendocrine carcinoma, as well as patients with adenocarcinoid, goblet cell
   carcinoid, or small cell carcinoma, or PNET patients with a Ki-67 proliferation index
   > 20 %.

   5. Patients with any of the following hematologic abnormalities at baseline:

      - Absolute neutrophil count < 1,500 per mm3

      - Platelet count < 100,000 per mm3

   6. Patients with any of the following serum chemistry abnormalities at baseline:

      - Total bilirubin > 1.5 × the ULN for the institution

      - AST or ALT > 3 × the ULN for the institution (> 5 × if due to hepatic involvement
      by tumor)

      - Creatinine > 1.5 × ULN for the institution

   7. Patients with any of the following coagulation parameter abnormalities at baseline:

      - PT (INR) > 1.5 × ULN for the institution

      - PTT > 1.5 × ULN for the institution

   8. Patients with:

      - Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism,
      within 6 months prior to first study drug administration; patients receiving
      systemic anti-coagulation for prophylactic or therapeutic reasons

      - Active uncontrolled bleeding or a known bleeding diathesis

   9. Patients with a significant cardiovascular disease or condition, including:

      - Congestive heart failure currently requiring therapy

      - Need for antiarrhythmic medical therapy for a ventricular arrhythmia

      - Severe conduction disturbance (e.g., 3rd degree heart block)

      - Angina pectoris requiring therapy

      - Known left ventricular ejection fraction < 50% by MUGA or echocardiogram

      - QTc interval > 450 msec in males, or > 470 msec in females

      - Uncontrolled hypertension (per the Investigator's discretion)

      - Class III or IV cardiovascular disease according to the New York Heart
      Association's Functional Criteria.

      - Myocardial infarction within 6 months prior to first study drug administration

10. Patients with a known or suspected hypersensitivity to any of the components of lipid
   nanoparticle-formulated DCR-MYC.

11. Patients with a known history of human immunodeficiency virus or active infection with
   hepatitis B virus or hepatitis C virus.

12. Patients with any other serious/active/uncontrolled infection, any infection requiring
   parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks prior to first
   study drug administration.

13. Patients with inadequate recovery from an acute toxicity associated with any prior
   antineoplastic therapy.

14. Patients with inadequate recovery from any prior surgical procedure, or patients
   having undergone any major surgical procedure within 4 weeks prior to first study drug
   administration.

15. Patients with any other life-threatening illness, significant organ system
   dysfunction, or clinically significant laboratory abnormality, which, in the opinion
   of the Investigator, would either compromise the patient's safety or interfere with
   evaluation of the safety of the study drug.

16. Patients with a psychiatric disorder or altered mental status that would preclude
   understanding of the informed consent process and/or completion of the necessary
   study-related evaluations.

17. Patients with the inability or with foreseeable incapacity, in the opinion of the
   Investigator, to comply with the protocol requirements.

Exclusion Criteria-Treatments:

   1. MTD PNET Cohort ONLY: Greater than 2 prior systemic treatments for the underlying
   malignancy

   2. Any antineoplastic agent for the primary malignancy (standard or experimental) within
   4 weeks prior to first study drug administration with the exception of monoclonal
   antibody therapy, nitrosoureas, and nitrogen mustard for the primary malignancy within
   6 weeks prior to first study drug administration

   3. Radiotherapy for the primary malignancy within 4 weeks prior to first study drug
   administration and during study.

   4. Herbal preparations or related over-the-counter preparations/supplements containing
   herbal ingredients within 2 weeks prior to first study drug administration and during
   study.

   5. Systemic hormonal therapy within 2 weeks prior to first study drug administration and
   during study.

   6. Any other investigational treatments during study. This includes participation in any
   medical device or therapeutic intervention clinical trials.

   7. Prophylactic use of hematopoietic growth factors within 1 week prior to first study
   drug administration and during Cycle 1 of study; thereafter prophylactic use of growth
   factors is allowed as clinically indicated.