Breast Neoplasms
Conditions
Keywords
HER2/HER3, Bispecific Antibody, Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer, HER2 Positive Breast Cancer, Trastuzumab, Herceptin
Brief summary
This is an open-label Phase 1 trial of MM-111 in combination with Herceptin.
Detailed description
Phase 1: Safety and tolerability of the MM-111 + Herceptin combination will be evaluated and the recommended Phase 2 dose will be determined.
Interventions
DRUGMM-111 + Herceptin
For Phase 1: Dose escalation cohorts, MM-111 and Herceptin are administered weekly or bi-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 breast cancer that is amplified for HER2, based on archived tumor biopsy (IHC 2+ or greater) * Patients must have histologically or cytologically confirmed advanced breast cancer that is heregulin positive based on fresh tumor tissue biopsy * The patient's cancer must have recurred, progressed or not responded to standard chemotherapy or other standard treatment. Prior therapies may include but are not limited to Herceptin, Tykerb (lapatinib), anthracyclines, and taxanes * 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 (per RECIST 1.1) or non-measurable tumor(s) (for Phase 1) * Patients should have ECOG Performance Score (PS) 0, 1 or 2 (for Phase 1). * Patients should have a life expectancy of at least 12 weeks * Patients must have adequate bone marrow reserves * Patients must have adequate hepatic function * Patients must have adequate renal function * Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy. * Women of childbearing potential as well as fertile men and their partners must agree 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 MM-111.
Exclusion criteria
* Patients who are pregnant or lactating * Patients with an active infection or with an unexplained fever \> 38.5°C (101.3° F) during screening visits or on the first scheduled day of dosing. * Patients with untreated and/or symptomatic metastatic CNS malignancies. * Patients with known hypersensitivity to any of the components of MM-111 or who have had hypersensitivity reactions to fully human monoclonal antibodies, including Herceptin. * Patients who have received other recent antitumor therapy including: * Treatment with Herceptin within the 28 days prior to the first scheduled day of dosing with MM-111 * Investigational therapy administered within the 28 days prior to the first scheduled day of dosing MM-111 (Dosing in less than 28 days' since receiving investigational therapy is acceptable once a time interval equal to at least five half-lives of the investigational agent has passed.) * Any standard chemotherapy, Tykerb (lapatinib) or radiation within 14 days (and having passed the time of any actual or anticipated toxicities) prior to the first scheduled dose of MM-111 * Patients who have previously received MM-111 * Patients with NYHA Class III or IV congestive heart failure or LVEF \< 50% * Patients with a history of allogeneic transplant * Patients with known HIV, hepatitis B or C (if patients have previously been treated for hepatitis C and have undetectable viral loads, they can be considered eligible for the trial) * Patients with any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Treatment-emergent AE's | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| To Determine the Recommended Phase 2 Doses of MM-111 + Herceptin in Combination | 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MM-111 + Herceptin MM-111 will be combined with Herceptin
MM-111 and Herceptin: For Phase 1: Dose escalation cohorts, MM-111 and Herceptin are administered weekly or bi-weekly via IV | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | MM-111 + Herceptin |
|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 11.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 2 / 16 |
Outcome results
Primary
Incidence of Treatment-emergent AE's
Time frame: 2 years
Population: Patients that received at least one dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MM-111 + Herceptin | Incidence of Treatment-emergent AE's | 16 participants |
Secondary
To Determine the Recommended Phase 2 Doses of MM-111 + Herceptin in Combination
Time frame: 2 years