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

• Sponsor: Merrimack Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00911898
• Collaborator: (none)
• Enrollment: 20
• Locations: 4
• Arm: 1
• Duration (Months): 33
• Patients Per Site: 5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Her2 Amplified Solid Tumors; Metastatic Breast Cancer	Drug: MM-111	Phase 1

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 and Pharmacologic Study of MM-111 in Patients With Advanced, Refractory Her2 Amplified, Heregulin Positive Cancers
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) or Maximum Feasible Dose [28 days]

   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.

Secondary Outcome Measures

1. 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]

2. To Explore the Role Functional Imagining (FDG-PET CT Scan), as a Predictor of Clinical Activity [December 2011]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	Indiana University (IUPUI)	Indianapolis	Indiana	United States	46268
3	Fox Chase Center	Philadelphia	Pennsylvania	United States	19111
4	South Texas Accelerated Research Therapeutics	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Merrimack Pharmaceuticals

Investigators

• Principal Investigator: Muralidhar Beeram, MD, The START Center for Cancer Care

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merrimack Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00911898
• Other Study ID Numbers: MM-111-01-100
• First Posted: Jun 3, 2009
• Last Update Posted: Jan 13, 2015
• Last Verified: Dec 1, 2014

• Keywords provided by Merrimack Pharmaceuticals: Her2 amplified solid tumors; Breast Cancer; Her3/ErbB3; Bispecific Antibody
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Arm/Group Title	MM-111
Arm/Group Description	MM-111: For Phase 1: Dose-escalation cohorts, drug is administered weekly via IV
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	MM-111
Arm/Group Description	MM-111: For Phase 1: Dose-escalation cohorts, drug is administered weekly via IV
Overall Participants	20
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61.0
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 60%
>=65 years	8 40%
Sex: Female, Male (Count of Participants)
Female	18 90%
Male	2 10%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Secondary Outcome

Title	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)
Time Frame	December 2011

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

2. Secondary Outcome

Title	To Explore the Role Functional Imagining (FDG-PET CT Scan), as a Predictor of Clinical Activity
Time Frame	December 2011

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Primary Outcome

Title	Maximum Tolerated Dose (MTD) or Maximum Feasible Dose
Description	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.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MM-111
Arm/Group Description	All participants
Measure Participants	20
Number [mg/kg]	NA

Adverse Events

Arm/Group Title	MM-111
Arm/Group Description	MM-111: For Phase 1: Dose-escalation cohorts, drug is administered weekly via IV
All Cause Mortality
	MM-111
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	MM-111
	Affected / at Risk (%)	# Events
Total	3/20 (15%)
General disorders
Disease Progression	1/20 (5%)
Infections and infestations
Acute viral myocarditis	1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Peural effusion	1/20 (5%)
Other (Not Including Serious) Adverse Events
	MM-111
	Affected / at Risk (%)	# Events
Total	5/20 (25%)
General disorders
Fatigue	5/20 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.