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2 week run-in of MM-121 followed by MM-121 + dosing of paclitaxel IV, followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.

Standard dosing of paclitaxel IV, followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.

MM-121 IV at 40 mg/mg loading dose on Cycle 1, Week 1 followed by 20 mg/mg weekly for all subsequent doses

MM-121

Victor Moyo, MD

To demonstrate whether addition of MM-121 to paclitaxel is more effective than treatment with paclitaxel alone, when administered as part of the neoadjuvant treatment in Her2 negative locally advanced operable breast cancer patients.

This is a multicenter, open-label, randomized, Phase II study of preoperative MM-121 with paclitaxel in HER2-negative breast cancer. Patients will be randomized to receive paclitaxel with or without MM-121 for 12 weeks followed by 4 cycles of doxorubicin plus cyclophosphamide and subsequent surgery.

A Trial of Preoperative MM-121 With Paclitaxel in HER2-negative Breast Cancer

A Randomized, Phase 2 Trial of Preoperative MM-121 With Paclitaxel in HER2-negative Breast Cancer

Pathologic Complete Response was defined as the absence of invasive cancer in the breast and lymph nodes following completion of neoadjuvant systemic therapy and reported according to the current AJCC staging system for neoadjuvant clinical studies. The endpoint was to determine the pathologic Complete Response (pCR) rates associated with weekly treatment of MM-121 plus paclitaxel followed by the combination treatment of doxorubicin plus cyclophosphamide compared with weekly paclitaxel alone followed by the combination treatment of doxorubicin plus cyclophosphamide in patients with human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer.

Sanofi

Merrimack Pharmaceuticals

All related AEs ongoing at the time of treatment discontinuation were followed until resolution. Investigators were to report any AEs/SAEs assumed to be related any time, even if occurring more than 30 days after last dose. Though different for each patient, on average, patients could be followed for related AEs/SAEs for \~1 year after termination.

Hormone-receptor positive (HR+) sub-group randomized to receive:

2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks)

HR+: MM-121+ Paclitaxel

Hormone-receptor positive (HR+) sub-group randomized to receive:

Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.

HR+: Paclitaxel Only

Triple Negative (TN) patients randomized to receive:

2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks)

TN: MM-121 + Paclitaxel

Triple negative (TN) patients randomized to receive:

Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.

TN: Paclitaxel

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Subject of Child-Bearing Potential (Y/N)

Clinical Trial Manager

Subjects with no pCR

Subjects with pCR

Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR)

Overall Study

Cisplatin

Cisplatin (50 mg/m2) in combination with doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) every 21 days and for a total of 6 cycles

cisplatin (50 mg/m2) in combination with doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) every 21 days and for a total of 6 cycles

José Bines, Doctorate

Otto Metzger, Oncologist

This is a single arm, single center, non-randomized, phase II trial of stage IIB/III TNBC. Patients received neoadjuvant chemotherapy with cisplatin (50 mg/m2) in combination with doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) every 21 days and for a total of 6 cycles. After surgery, adjuvant chemotherapy consisting of docetaxel (75 mg/m2) every 21 days was further provided for 4 cycles. Primary outcome was pathological complete response in the breast and axilla (pCR; ypT0ypN0). Secondary outcomes were safety, disease-free survival and overall survival.

This is a non-randomized, open-label, single arm, single center, phase II clinical trial. Patients received neoadjuvant chemotherapy with cisplatin (50 mg/m2, intravenous \[IV\], day 1) in combination with doxorubicin (50 mg/m2, IV, day 1) and cyclophosphamide (500 mg/m2, IV, day 1) every 21 days and for a total of 6 cycles (CAP regimen). Subsequent mastectomy plus axillary lymph node dissection was performed. Pathological specimen was analyzed to assess tumor response in the breast and axilla. Adjuvant chemotherapy consisting of docetaxel (75 mg/m2, IV) every 21 days was further provided for 4 cycles. In case of tumor progression during neoadjuvant treatment, CAP was discontinued and additional local or systemic treatment was provided at the discretion of the investigator. The protocol was approved by the institutional review board of National Cancer Institute - Brazil. All patients provided written informed consent. The Brazilian Group of Breast Cancer Studies (GBECAM) and National Cancer Institute -Brazil were the academic sponsors and National Cancer Institute- Brazil was the funding source of the trial.

Study of Neoadjuvant Treatment of Locally Advanced Breast Cancer With CAP Regimen

Phase II Study of Neoadjuvant Treatment of Locally Advanced Breast Cancer Patients With the CAP Regimen

All data from this study was monitored by the GBECAM (Brazilian Group of studies on breast cancer) and the protocol approved by the research ethics committee of the National Cancer Institute.

The collected data are archived in the research center, available for consultation in individual clinical records by patients, in addition to the source documents and folders with all regulatory material of the study.

We are in the process of finalizing a scientific paper, to be published in an international magazine, in order to disseminate the results of the study.

Pathological complete response (pCR) assessed by the local pathology lab, and defined as the absence of tumor (invasive and/or in situ) both in the breast and axilla (ypT0 ypN0)

Safety was assessed according to NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0.

DFS was defined as time from surgery to disease recurrence or death from any cause

OS was defined as time from surgery to death from any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Trial of Preoperative MM-121 With Paclitaxel in HER2-negative Breast Cancer	NCT01421472	ER Positive, He... Triple Negative...	MM-121 Paclitaxel	18 Years -	Merrimack Pharmaceuticals
Study of Neoadjuvant Treatment of Locally Advanced Breast Cancer With CAP Regimen	NCT03304756	Triple Negative...	CAP	18 Years -	Instituto Nacional de Cancer, Brazil

Spots Global Cancer Trial Database for triple negative breast cancer patients