Phase 1
Completed N=45
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
Solid Tumors · ER/PR Positive Breast Cancer · Triple-Negative Breast Cancer · Metastatic Breast Cancer With Active Brain Metastasis
Source: ClinicalTrials.gov NCT01770353 ↗
Enrolled (actual)
45
Serious AEs
50.0%
Results posted
Oct 2019
Primary outcomePrimary: Pilot Phase: Tumour Levels of Irinotecan and SN-38 at Cycle 1 Day 4 — 4253; 38.1 nanograms per gram (ng/g)
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pilot Phase: Tumour Levels of Irinotecan and SN-38 at Cycle 1 Day 4 |
4253; 38.1 | — |
| PRIMARY Expansion Phase: Impact of the Quality of MRI Scan on Tumour Evaluation |
4; 3; 7; 3; 2; 4 | — |
| PRIMARY Expansion Phase: Best Overall Tumour Response (BOR) by Tumour FMX Uptake Classification at 16 - 24 Hours Post-FMX Dose |
1; 0; 0; 1; 3; 0 | — |
| SECONDARY Pilot Phase + Expansion Phase: Median Progression-free Survival (PFS) (Non-CNS Assessment) |
1.8; 1.9; 4.3; 3.2 | — |
| SECONDARY Expansion Phase: Median PFS for Cohort 3 (CNS Assessment) |
3.6 | — |
| SECONDARY Pilot Phase + Expansion Phase: BOR (Non-CNS Assessment) |
0; 0; 0; 0; 1; 4 | — |
| SECONDARY Expansion Phase: BOR for Cohort 3 (CNS Assessment) |
0; 3; 3; 0; 2; 2 | — |
| SECONDARY Pilot Phase + Expansion Phase: Objective Response Rate (ORR) (Non-CNS Assessment) |
7.7; 40.0; 33.3; 30.0 | — |
| SECONDARY Expansion Phase: ORR for Cohort 3 (CNS Assessment) |
30.0 | — |
| SECONDARY Pilot Phase + Expansion Phase: Median Duration of Objective Response (DOR) (Non-CNS Assessment) |
3.84; 7.46; 5.62; 4.14 | — |
| SECONDARY Expansion Phase: Median DOR for Cohort 3 (CNS Assessment) |
1.84 | — |
| SECONDARY Pilot Phase + Expansion Phase: Clinical Benefit Response (CBR) (Non-CNS Assessment) |
15.4; 40.0; 33.3; 30.0 | — |
| SECONDARY Expansion Phase: CBR for Cohort 3 (CNS Assessment) |
50.0 | — |
| SECONDARY Pilot Phase + Expansion Phase: Number of Subjects Who Experienced Treatment Emergent Adverse Events (TEAEs) Related to MM-398 |
13; 28 | — |
| SECONDARY Pilot Phase: Time to Reach Maximum Plasma Concentration of Irinotecan and SN-38 (Tmax) |
1.72; 3.20 | — |
| SECONDARY Expansion Phase: Irinotecan and SN-38 Tmax |
NA; 1.71; 1.73; NA; 3.03; 2.12 | — |
| SECONDARY Pilot Phase: Maximum Observed Plasma Concentration of Irinotecan (Cmax) |
39.0 | — |
| SECONDARY Pilot Phase: SN-38 Cmax |
2.40 | — |
| SECONDARY Expansion Phase: Irinotecan Cmax |
NA; 28.1; 44.4; NA; 30.4; 46.6 | — |
| SECONDARY Expansion Phase: SN-38 Cmax |
3.08; 3.63; NA; 2.60; NA | — |
| SECONDARY Pilot Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC[0-tlast]) for Irinotecan |
1721 | — |
| SECONDARY Pilot Phase: SN-38 AUC(0-tlast) |
212 | — |
| SECONDARY Expansion Phase: Irinotecan AUC(0-tlast) |
NA; 1430; 1530; NA; 1589; 1788 | — |
| SECONDARY Expansion Phase: SN-38 AUC(0-tlast) |
237; NA; NA; 214; NA | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01770353). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.