NCT03285607

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

Withdrawn Phase 1 Last updated 16 August 2018

What this trial tests

Phase 1 trial testing MCS110 in Breast Cancer. Withdrawn.

Timeline

30 September 2018

Primary endpoint
31 October 2019

28 February 2021

Quick facts

Lead sponsor	Washington University School of Medicine
Phase	Phase 1
Status	Withdrawn
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Start date	30 September 2018
Primary completion	31 October 2019
Estimated completion	28 February 2021

Drugs / interventions tested

• MCS110
• Doxorubicin
• Cyclophosphamide (cyclophosphamide) — full drug profile →
• Paclitaxel — full drug profile →
• Bone marrow aspirate
• Peripheral blood samples — full drug profile →
• Tumor tissue (tumor-tissue) — full drug profile →

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →
• Cancer of Breast — all drugs for Cancer of Breast →

Sponsor

Washington University School of Medicine

Who can join

18 and older, any sex, with Breast Cancer or Cancer of Breast. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immune Infiltrates in Breast Cancer: Recent Updates and Clinical Implications.
   Dieci MV, Miglietta F, Guarneri V. · · 2021 · cited 168× · PMID 33498711 · DOI 10.3390/cells10020223
2. Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy.
   He Y, de Araújo Júnior RF, Cruz LJ, Eich C. · · 2021 · cited 48× · PMID 34683963 · DOI 10.3390/pharmaceutics13101670
3. The role of macrophages-mediated communications among cell compositions of tumor microenvironment in cancer progression.
   Li M, Jiang P, Wei S, Wang J, et al · · 2023 · cited 30× · PMID 36845095 · DOI 10.3389/fimmu.2023.1113312
4. Despicable role of epithelial-mesenchymal transition in breast cancer metastasis: Exhibiting <i>de novo</i> restorative regimens.
   Famta P, Shah S, Dey B, Kumar KC, et al · · 2025 · cited 7× · PMID 39872366 · DOI 10.1016/j.cpt.2024.01.001