MM-398 (Nanoliposomal Irinotecan, Nal-IRI) to Determine Tumor Drug Levels and to Evaluate the Feasibility of Ferumoxytol Magnetic Resonance Imaging to Measure Tumor Associated Macrophages and to Predict Patient Response to Treatment


About this study

This is a Phase I study to understand the biodistribution of MM-398 and to determine the feasibility of using Ferumoxytol as a tumor imaging agent.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Pathologically confirmed diagnosis of solid tumors, CRC, TNBC, ER/PR Breast Cancer, NSCLC, Pancreatic Cancer, Ovarian Cancer, Gastric Cancer, GEJ adenocarcinoma, Head and Neck Cancer
  • Metastatic disease
  • ECOG Performance Status 0 to 2
  • Adequate bone marrow, hepatic and renal function
  • Normal ECG
  • 18 years of age or above
  • Able to understand and sign informed consent

Expansion Phase Additional Criteria:

The following invasive breast cancer tumor sub-types are required:

  • Cohorts 1 and 2 must be documented to be HER2 negative as outlined in the ASCO/CAP 2013 guidelines for HER2 testing, defined by at least one of the following:
    • HER2 immunohistochemistry (IHC) staining of 0 or 1+,OR if HER2 IHC 2+
    • Negative by In-Situ Hybridization (ISH) based on defined as a Single probe average HER2 copy number <4.0 signals/cell
    • OR Negative by Dual-probe ISH defined as a HER2/CEP17 ratio <2.0 with an average HER2 copy number <4.0 signals/cell
  • Cohort 1: hormone receptor positive breast cancer patients with ER-positive and/or PR-positive tumors defined as ≥1% of tumor nuclei that are immunoreactive for ER and/or PR and HER2 negative
  • Cohort 2: triple negative breast cancer (TNBC) patients with ER-negative, PR-negative tumors defined as < 1% of tumor nuclei that are immunoreactive for ER and PR and HER2 negative
  • Cohort 3: Any sub-type of metastatic breast cancer and active brain metastases
  • Documented locally advanced or metastatic disease with at least two radiologically measurable lesions as defined by RECIST v1.1 (except Expansion Cohort 3)
  • ECOG performance status 0 or 1
  • Bone marrow reserves as evidenced by: ANC > 1,500 cells/μl without the use of hematopoietic growth factors; Platelet count > 100,000 cells/μl; Hemoglobin > 9 g/dL
  • Adequate hepatic function as evidenced by: Normal serum total bilirubin; AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN is acceptable if liver metastases are present)
  • Adequate renal function as evidenced by serum creatinine ≤ 1.5 x ULN
  • Normal ECG or ECG without any clinically significant findings
  • Recovered from the effects of any prior surgery, radiotherapy or other anti-neoplastic therapy
  • At least 18 years of age
  • Able to understand and sign an informed consent (or have a legal representative who is able to do so)
  • Received at least one cytotoxic therapy in the locally advanced and metastatic setting, with exception of TNBC patients who progressed within 12 months of adjuvant therapy
  • Received 5 prior lines of chemotherapy in the metastatic setting (no limit to prior lines of hormonal therapy in Cohort 1)
  • At least one lesion amenable to multiple pass core biopsy (exception: Cohort 3 patients)
  • Candidate for chemotherapy

Expansion Phase Cohort 3 additional inclusion criteria:

  • Radiographic evidence of new or progressive brain metastases after prior radiation therapy with at least one brain metastasis measuring ≥ 1 cm in longest diameter on gadolinium-enhanced MRI (note: progressive brain lesions are not required to meet RECIST criteria in order to be eligible; extra-cranial metastatic disease is also allowed)
  • Neurologically stable
  • No evidence of diffuse leptomeningeal disease on brain MRI or by previously documented cerebrospinal fluid (CSF) cytology. NOTE: discrete dural metastases are permitted.

Exclusion Criteria:

  • Active CNS metastasis (applies to pilot phase and expansion phase cohort 1 and 2 only)
  • Clinically significant GI disorders
  • Prior irinotecan or bevacizumab therapy within last 6 months and for Expansion Phase patients, have received any prior treatment with Topol inhibitor
  • Known hypersensitivity to MM-398 or ferumoxytol
  • Inability to undergo MRI
  • Active infection
  • Pregnant or breast feeding
  • Prior chemotherapy administered within 3 weeks, or within a time interval less than at least 5 half-lives of the agent, whichever is longer, prior to the first scheduled day of dosing in this study
  • Received radiation therapy in the last 14 days
  • Treated with parenteral iron in the previous 4 weeks

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Donald Northfelt, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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