Dataset Information

Phase Ib clinical trial of the anti-frizzled antibody vantictumab (OMP-18R5) plus paclitaxel in patients with locally advanced or metastatic HER2-negative breast cancer.

ABSTRACT:

Purpose

Vantictumab is a monoclonal antibody that binds to frizzled (FZD) receptors and inhibits canonical WNT signaling. This phase Ib dose escalation study enrolled patients with locally recurrent or metastatic HER2-negative breast cancer who were treated with weekly paclitaxel in combination with escalating doses of vantictumab.

Methods

Patients were enrolled in dose escalation cohorts treated with weekly paclitaxel 90 mg/m² on days 1, 8 and 15 in combination with vantictumab 3.5-14 mg/kg days 1 and 15 or 3-8 mg/kg day 1 of every 28-day cycle. Primary endpoints were safety, dose-limiting toxicities (DLTs). Secondary endpoints included pharmacokinetics, efficacy and an exploratory biomarker analysis.

Results

Forty-eight female patients with a mean age of 54 were enrolled. The majority (66.6%) received prior chemotherapy for recurrent or metastatic disease; 45.8% were hormone receptor (HR)-positive, HER2-negative and 54.2% triple-negative. The most frequent adverse events related to any study treatment were nausea (54.2%), alopecia (52.1%), fatigue (47.9%), and peripheral neuropathy (43.8%). No DLTs occurred; however, 6 patients experienced fractures outside of the DLT window. The overall response rate was 31.3% and the clinical benefit rate was 68.8%. A 6-gene WNT pathway signature showed significant association with progression-free survival (PFS) and overall survival (OS) for the biomarker high versus biomarker low groups (PFS: p = 0.029 and OS: p = 0.00045, respectively).

Conclusions

The combination of vantictumab and weekly paclitaxel was generally well tolerated with promising efficacy; however, the incidence of fractures limits future clinical development of this particular WNT inhibitor in metastatic breast cancer.

Clinical trial registration

ClinicalTrials.gov registration: NCT01973309.

SUBMITTER: Diamond JR

PROVIDER: S-EPMC7572714 | biostudies-literature |

REPOSITORIES: biostudies-literature

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