Her2 Amplified Solid Tumors, Metastatic Breast Cancer
Conditions
Keywords
Her2 amplified solid tumors, Breast Cancer, Her3/ErbB3, Bispecific Antibody
Brief summary
This study is an open-label Phase 1 trial of MM-111.
Detailed description
Phase 1: Patients with any solid tumor type may be enrolled to evaluate the safety and tolerability of MM-111.
Interventions
DRUGMM-111
For Phase 1: Dose-escalation cohorts, drug is administered weekly via IV
Sponsors
Merrimack Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MM-111 MM-111: For Phase 1: Dose-escalation cohorts, drug is administered weekly via IV | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | MM-111 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 61.0 years |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 20 |
| serious Total, serious adverse events | 3 / 20 |
Outcome results
Primary
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.
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MM-111 | Maximum Tolerated Dose (MTD) or Maximum Feasible Dose | NA mg/kg |
Secondary
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
Secondary
To Explore the Role Functional Imagining (FDG-PET CT Scan), as a Predictor of Clinical Activity
Time frame: December 2011