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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1 Multi Arm Study Evaluating the Safety, Pharmacology and Preliminary Activity of the Co-Administration of MM-151 With Seribantumab (MM-121), Istiratumab (MM-141), or Trametinib in Biomarker-selected Cancer Patients

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

Intervention / Treatment
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* Drug: MM-151
* Drug: MM-121
* Drug: MM-141
* Drug: trametinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MM-151+MM-121 Dose Escalation<br>MM-151 and MM-121 dose escalation in lung, head and neck, and colorectal cancers | Drug: MM-151<br>* MM-151<br>Drug: MM-121<br>* MM-121<br>|
| Experimental: MM-151+ trametinib Dose Escalation<br>MM-151 and trametinib dose escalation in lung, head and neck, and colorectal cancers. | Drug: MM-151<br>* MM-151<br>Drug: trametinib<br>* trametininb<br>* Other names: MEKINIST;|
| Experimental: MM-151+MM-141 Dose Escalation<br>MM-151 and MM-141 dose escalation in lung, head and neck, and colorectal cancers | Drug: MM-151<br>* MM-151<br>Drug: MM-141<br>* MM-141<br>|
| Experimental: MM-151+trametinib Dose Escalation<br>MM-151 and trametinib dose escalation in lung, head and neck, and colorectal cancers. | Drug: MM-151<br>* MM-151<br>Drug: trametinib<br>* trametininb<br>* Other names: MEKINIST;|
| Experimental: Colorectal cancer Expansion<br>Doses established in part 1 of the study | Drug: MM-151<br>* MM-151<br>Drug: MM-121<br>* MM-121<br>Drug: MM-141<br>* MM-141<br>Drug: trametinib<br>* trametininb<br>* Other names: MEKINIST;|
| Experimental: Head and neck Expansion<br>Doses established in part 1 of the study | Drug: MM-151<br>* MM-151<br>Drug: MM-121<br>* MM-121<br>Drug: MM-141<br>* MM-141<br>Drug: trametinib<br>* trametininb<br>* Other names: MEKINIST;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heregulin-positive, EGFR, ErbB3, Phase I, Oncology, Cancer, IGF-1, MEKinhibitor, IGF-1R inhibitor, KRAS, NRAS