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

This study is conducted over two phases. The pilot phase of this trial is closed. The
expansion phase of this trial has completed enrolment, patients are still ongoing.

Pilot Phase: This study will enroll approximately 12 patients, up to 20 in total in the Pilot
Phase and 30 patients in the Expansion Phase. The first three patients that are enrolled in
the Pilot Phase can have any solid tumor type; however subsequent patients must have
Non-small cell lung cancer (NSCLC), Colorectal cancer (CRC), Triple negative breast cancer
(TNBC), Estrogen Receptor/Progesterone Receptor (ER/PR) positive breast cancer, pancreatic
cancer, ovarian cancer, gastric cancer, gastro-oesophageal junction adenocarcinoma or head
and neck cancer. No more than three patients with ER/PR positive breast cancer can be
enrolled in the Pilot Phase and similar restrictions may be placed on other tumor types to
ensure a heterogeneous population.

Expansion Phase: The expansion will enroll patients with advanced metastatic breast cancer
into three cohorts of 10 patients each depending on sub-type of breast cancer:

Cohort 1: ER and/or PR-positive breast cancer Cohort 2: TNBC Cohort 3: BC with active brain
metastasis

Inclusion Criteria:

All subjects:

- Pathologically confirmed diagnosis of solid tumors

- Metastatic disease

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1

- Adequate bone marrow, hepatic and renal function

- Normal Electrocardiogram (ECG)

- 18 years of age or above

- Able to understand and sign informed consent

Pilot study only:

- CRC, TNBC, ER/PR Breast Cancer, NSCLC, Pancreatic Cancer, Ovarian Cancer, Gastric Cancer,
Gastroesophageal Junction (GEJ) adenocarcinoma, Head and Neck Cancer

Expansion Phase Additional Criteria:

- Locally advanced or metastatic breast cancer

- Received at least one cytotoxic therapy in the locally advanced and metastatic setting

- Received ≤ 5 prior lines of chemotherapy in the metastatic setting

- Candidate for chemotherapy

Expansion Phase Cohort 3 additional inclusion criteria:

- Breast cancer with active brain metastasis

- Neurologically stable

Exclusion Criteria:

- Active Central nervous system (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