A phase 1b/2a study evaluating the combination of MM-151 + nal-IRI + 5-FU + Leucovorin in RAS/RAF wild-type Metastatic Colorectal Cancer.
Part 1: Patients will be enrolled to determine the maximum tolerated dose, safety and tolerability of MM-151 + nal-IRI + 5-FU + LV in patients with mCRC that are RAS/RAF wild-type. Part 2: Patients will be enrolled at the maximum tolerated dose of MM-151 in combination with nal-IRI + 5-FU + LV to characterize initial efficacy in conjunction with levels of irinotecan and SN-38 measured in tissue.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
To find the phase II dose of MM-151 based on safety and tolerability of MM-151 + nal-IRI + 5-FU + Leucovorin that will be assessed through evaluation of dose limiting toxicity reporting.
Time frame: The DLT timeframe is from date of first dose up until 42 days after that date
To correlate disease response according to RECIST with levels of irinotecan and SN-38 in tumor tissue
Time frame: 2 years
The number of participants with adverse events (AE) related to treatment with MM-151 + nal-IRI + 5-FU + leucovorin, assessed according to NCI CTCAE v4.0
These will be described by abnormalities in hematology, blood chemistry and other laboratory abnormalities, ECG, physical examination, vital signs and other safety parameters. Frequency, duration and severity of the adverse events according to NCI CTCAE v4.0 will be assessed.
Time frame: 2 years
The PK parameters of MM-151 and nal-IRI will be described per Cmax
Time frame: Priming Phase Day 1, Priming Phase Day 8, C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C2D17, C2D22, C3D1, C5D1
The PK parameters of MM-151 and nal-IRI will be described per AUC
Time frame: Priming Phase Day 1, Priming Phase Day 8, C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C2D17, C2D22, C3D1, C5D1
Objective response based on RECIST
Time frame: 2 years
Measure pre-treatment and on-treatment levels of EGFR ligands
Time frame: 2 years
Presence of anti-drug antibodies will be assessed
Time frame: 2 years
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Chemotherapy