Phase 1 Combination Study of MM-151 With MM-121, MM-141, or Trametinib

Merrimack Pharmaceuticals

Status and phase: Terminated; Phase 1

Conditions: Squamous Cell Carcinoma of the Head and Neck; Non-small Cell Lung Cancer; Colorectal Cancer

Treatments: Drug: MM-151; Drug: trametinib; Drug: MM-141; Drug: MM-121

Study type: Interventional

Funder types: Industry

Identifiers

NCT02538627

MM-151-01-01-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 5 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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5 participants in 6 patient groups

MM-151+MM-121 Dose Escalation

Experimental group

Description:

MM-151 and MM-121 dose escalation in lung, head and neck, and colorectal cancers

Treatment:

Drug: MM-151

Drug: MM-121

MM-151+ trametinib Dose Escalation

Experimental group

Description:

MM-151 and trametinib dose escalation in lung, head and neck, and colorectal cancers.

Treatment:

Drug: MM-151

Drug: trametinib

MM-151+MM-141 Dose Escalation

Experimental group

Description:

MM-151 and MM-141 dose escalation in lung, head and neck, and colorectal cancers

Treatment:

Drug: MM-151

Drug: MM-141

MM-151+trametinib Dose Escalation

Experimental group

Description:

MM-151 and trametinib dose escalation in lung, head and neck, and colorectal cancers.

Treatment:

Drug: MM-151

Drug: trametinib

Colorectal cancer Expansion

Experimental group

Description:

Doses established in part 1 of the study

Treatment:

Drug: MM-151

Drug: trametinib

Drug: MM-121

Drug: MM-141

Head and neck Expansion

Experimental group

Description:

Doses established in part 1 of the study

Treatment:

Drug: MM-151

Drug: trametinib

Drug: MM-121

Drug: MM-141