Summary of Clinical Use

A Phase 2 clinical trial of MCS110 (given with 7624 and 4793) in patients with advanced triple negative breast cancer (TNBC) is underway (NCT02435680). In these patients MCS110 is expected to enhance the effects of the other chemotherapy agents by eliminating tumour-associated macrophages (TAMs). Another Phase 2 trial in patients with pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCTTS) is underway (NCT01643850). PVNS is a rare joint cancer driven by aberrant CSF-1 production> High levels of CSF-1 attracts an abnormal number of macrophages in to the joints. PVNS tumor tissue is largely composed of CSF-1 responsive (i.e. CSF1R +ve) macrophages.

Mechanism Of Action and Pharmacodynamic Effects

MCS110 blocks the ability of colony stimulating factor 1 (CSF-1 a.k.a. M-CSF) to drive proliferation in responsive cells. In immuno-oncology anti-CSF-1 antibodies are hypothesized to reduce tumor-associated macrophages (TAMs) which appear to actively promote all aspects of tumor initiation, growth, and development. Blocking this activity should provide anti-cancer and anti-inflammatory effects. Other CSF-1 actions: CSF-1 promotes the differentiation of osteoclasts from precursor cells of the monocytic lineage, and CSF-1 secretion by invasive tumor cells is thought to drive aberrant osteoclastogenesis and bone degradation in cancer patients withbone metastases. It is hypothesised that blocking abberant CSF-1-CSF1R activation will reduce the skeletal-related events in this patient group. However, a Phase I clinical trial (NCT00757757) in patients with prostate cancer and bone metastases was terminated.

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT01643850	MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)	Phase 2 Interventional	Novartis
NCT02435680	Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)	Phase 2 Interventional	Novartis