Colorectal Cancer, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of the Head and Neck
Conditions
Keywords
Heregulin-positive, EGFR, ErbB3, Phase I, Oncology, Cancer, IGF-1, MEKinhibitor, IGF-1R inhibitor, KRAS, NRAS
Brief summary
This is a Phase 1 open-label, dose-escalation trial using 3+3 design, evaluating MM-151 co-administration with MM-121, MM-141, and trametinib at varying dose levels.
Detailed description
This is a two-part Phase 1, non-randomized, open-label study of MM-151 plus MM-121, MM-141, or trametinib in patients with advanced, heregulin-positive lung, head and neck, and colorectal cancers. In part 1 of the study, cohorts of 3 or more patients will be treated at escalating doses of MM-151 in combination with MM-121, MM-141, and trametinib until a maximum tolerated combination dose for each combination is identified. In part 2 of the study, patients will be treated with the combination dose identified in part 1 of the study.
Sponsors
Merrimack Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be \>18 years of age * Patients must be able to provide informed consent * Willing to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of any study therapy). This applies to women of childbearing potential as well as fertile men and their partners * Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy, up to CTCAE grade 1 * Patients must have either heregulin-positive cancer, cancer with RAS mutation, IGF-1 positive cancer, or RAS wild type cancer.
Exclusion criteria
* Patients who are pregnant or lactating * Patients who have an active infection or with an unexplained fever \> 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumor fever may be enrolled.) * Patients with untreated (primary) or symptomatic CNS (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least 2 weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial. * Patients who have received other recent antitumor therapy including any standard chemotherapy or radiation within 14 days (and having passed the time of any actual or anticipated toxicities) prior to the first scheduled dose of the study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To find a phase II dose of MM-151 in combination with MM-121, MM-141, and trametinib based on maximum tolerated dose (MTD) in patients with lung, head and neck, and colorectal cancers | 1.5 years |
Secondary
| Measure | Time frame |
|---|---|
| Number of dose limiting toxicities (DLTs) within a group | 1.5 years |
| Adverse event profile of MM-151 in combination with MM-121, MM-141, and trametinib | 1.5 years |
| Objective response to MM-151 in combination with MM-121, MM-141, and trametinib based on RECIST | 1.5 years |
Countries
United States
Outcome results
None listed