A Study of MM-111 in Patients With Advanced, Refractory Her2 Amplified, Heregulin Positive Cancers (Monotherapy)

A Phase 1 and Pharmacologic Study of MM-111 in Patients With Advanced, Refractory Her2 Amplified, Heregulin Positive Cancers

This study is an open-label Phase 1 trial of MM-111.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer; Her2 Amplified Solid Tumors
• Intervention / Treatment: Drug: MM-111

Detailed Description

Phase 1: Patients with any solid tumor type may be enrolled to evaluate the safety and tolerability of MM-111.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California Norris Comprehensive Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46268
      • Indiana University (IUPUI)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed advanced cancer that is:

  • HER2 amplified (IHC 2+ or greater) based on archived tumor evaluation
  • Heregulin positive based on a study required fresh biopsy sample performed at screening and confirmed by central laboratory
• Patients must have blocks of archived formalin-fixed, paraffin-embedded tumor tissue available for sectioning and immunohistochemical staining
• Patient's cancer must have recurred or progressed following standard therapy, have not responded to standard therapy, or for which no standard therapy exists.
• Patients must be >= 18 years of age
• Patients or their legal representatives must be able to understand and sign an informed consent
• Patients may have measurable or non-measurable tumor(s)
• Patients should have ECOG Performance Score (PS) 0 or 1

• Patients must have adequate bone marrow reserves as evidenced by:

  • Absolute neutrophil count (ANC) >= 1,500/uL and
  • Platelet count >= 100,000/uL
  • Hemoglobin >= 9 g/dL
• Patients must have tumor tissue amenable to biopsy
• Patients must be willing to undergo biopsy prior to treatment to MM-111

Exclusion Criteria:

• Patients for whom potentially curative antineoplastic therapy is available
• Patients who are pregnant or lactating
• Patients with an active infection or with an unexplained fever greater than 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 and/or symptomatic primary or metastatic CNS malignancies (patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial
• Patients with known hypersensitivity to any of the components of MM-111 or who have had hypersensitivity reactions to fully human monoclonal antibodies (patients with a history of hypersensitivity to trastuzumab, a humanized antibody, are not excluded)
• Patients with known HIV, hepatitis B or C (if patients have previously been treated for C and have undetectable viral loads, they can be considered eligible for the trial)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MM-111	Drug: MM-111; For Phase 1: Dose-escalation cohorts, drug is administered weekly via IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) or Maximum Feasible Dose	The Maximum Tolerated Dose (MTD) was defined as the highest dose level in which a DLT is experienced by fewer than two patients in a cohort of 3 - 6 patients. If a DLT is observed in at least two patients in a cohort of 3 - 6 patients, the MTD will be determined to have been exceeded and an additional three patients (up to a total of six) are to be treated at the next lower dose level.	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
To Determine the Clinical Activity of MM-111 in Patients Based on Objective Response Rate (ORR), Duration of Response (DoR), Progression Free Survival (PFS), and 16 & 24-week Clinical Benefit Rate (CBR)	December 2011
To Explore the Role Functional Imagining (FDG-PET CT Scan), as a Predictor of Clinical Activity	December 2011

Collaborators and Investigators

• Sponsor: Merrimack Pharmaceuticals
• Investigators: Principal Investigator: Muralidhar Beeram, MD, The START Center for Cancer Care

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: June 2, 2009
• First Submitted That Met QC Criteria: June 2, 2009
• First Posted (Estimate): June 3, 2009

Study Record Updates

• Last Update Posted (Estimate): January 13, 2015
• Last Update Submitted That Met QC Criteria: December 30, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Breast Cancer; Bispecific Antibody; Her2 amplified solid tumors; Her3/ErbB3
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: MM-111-01-100