MCS110 Combined With Neoadjuvant Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer

Summary

In patients with locally advanced hormone receptor positive (HR+)/HER2- breast cancer, neoadjuvant chemotherapy produces a pathologic complete response rate (pCR) of only 9-15%, and late recurrences often occur despite neoadjuvant chemotherapy. Therefore, there is an unmet clinical need to improve the outcomes of these patients. Tumor-associated macrophages (TAM) infiltration leads to poor outcomes in breast cancer patients by promoting angiogenesis, activating epithelial-mesenchymal transition, degrading the extracellular matrix, and suppressing the anti-tumor immune response. Pre-clinical studies, as summarized above, have shown that the breast cancer immune microenvironment may be reprogrammed by targeting colony-stimulating factor-1 (CSF-1) to decrease TAM infiltration and increase CD8+ TIL infiltration, in order to foster antitumor immunity and improve response to therapy.

Here, the investigators propose a phase I dose-escalation study in patients with locally advanced HR+/HER2- breast cancer to determine the feasibility of adding MCS110, a CSF-1 inhibitor, to the standard neoadjuvant chemotherapy regimen of dose-dense doxorubicin, cyclophosphamide followed by paclitaxel. The investigators will also include a dose expansion cohort for preliminary efficacy analysis and correlative studies. The investigators propose that if they can decrease the TAM-induced immunosuppression and TAM-induced chemoresistance observed in breast cancer patients, then the patients' own immune system could find and destroy the dormant and resistant tumor cells, and combined with enhanced chemotherapy efficacy, the investigators will see durable remissions and long term cures.

Conditions

• Breast Cancer
• Cancer of Breast

Interventions

BIOLOGICAL

MCS110

-MCS110 is an IgG1/κ humanized monoclonal antibody directed against human macrophage colony stimulating factor

DRUG

Doxorubicin

-Standard of care

DRUG

Cyclophosphamide

-Standard of care

DRUG

Paclitaxel

-Standard of care

PROCEDURE

Bone marrow aspirate

-Time of enrollment and at time of surgery

PROCEDURE

Peripheral blood samples

-Time of enrollment and at time of surgery

PROCEDURE

Tumor tissue

-Time of enrollment and at time of surgery

Sponsors & Collaborators

• Novartis Pharmaceuticals

  collaborator INDUSTRY

• Washington University School of Medicine

  lead OTHER

Principal Investigators

• Leonel Hernandez-Aya, M.D. · Washington University School of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-09-30

Primary Completion

2019-10-31

Completion

2021-02-28

FDA Drug

Yes