Date: 2014-05-31
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 50th American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 to June 3, 2014, in Chicago
Company: Roche (Switzerland)
Product: RG7155
Action
mechanism: RG7155 is an investigational humanized monoclonal IgG1 antibody designed to target and deplete tumor-associated macrophages (TAMs) in the tumor tissue. TAMs are an abundant component of the tumor microenvironment of many tumor types supporting tumorigenesis by suppressing the local immune system and promoting growth of tumor cells. RG7155 specifically targets TAMs by binding to colony-stimulating factor-1 receptor (CSF-1R) on the cell surface and blocking its activation by CSF-1. RG7155 therapy has been shown to significantly reduce CSF-1 dependent macrophages in PVNS and in tumors of cancer patients.
Disease: locally advanced pigmented villonodular synovitis (PVNS)
Therapeutic area: Cancer - Oncology
Country:
Trial
details: BP27772 is an open-label, multicenter, dose escalation Phase Ia/Ib study with extension phase to evaluate safety, pharmacokinetics and activity of RG7155, administered as an intravenous infusion as monotherapy and in combination with paclitaxel in patients with advanced solid tumors. 124 patients have been enrolled including 22 patients (DE and extension) with inoperable progressive or relapsing PVNS. To date clinical activity was evaluated in 17 respectively 18 patients using FDG-PET (at 4 weeks after treatment start; EORTC criteria) and MRI (at 6 weeks; RECIST 1.1). Pre- and on-treatment biopsies of tumor and surrogate skin tissue as well as peripheral blood PD markers were analyzed. RG7155 is further explored in monotherapy extension cohorts in mesothelioma, pancreatic, breast and ovarian cancer. In addition, a combination arm with weekly paclitaxel in metastatic breast cancer and ovarian cancer is ongoing. The Phase I DE and extension study enrolled 22 patients with inoperable progressive or relapsing PVNS. Treatment with RG7155 resulted in rapid onset of functional and symptomatic improvement occurring in the vast majority of patients within the first 3 infusions given every 2 weeks. Tumor MRI assessment was performed at baseline and at 6 weeks on treatment with follow up assessments every 6 weeks. 15/18 patients assessed (83%) showed a time point partial response (MRI at 6 weeks according to RECIST version 1.1.). In addition, 15/17 patients assessed (88%) showed a partial metabolic response (FDG-PET at 4 weeks, EORTC criteria). Currently, all except one patient remain clinically progression free (longest follow up 22 months). Patients received doses from 900 mg onwards, escalating to 1350 mg and 2000 mg, respectively. The maximum tolerated dose (MTD) was not reached and the optimal biological dose (OBD) for the extension cohort (1000 mg) was defined based on PD biomarker read-outs.
Latest
news: * On May 31, 2014, Roche announced that the company will present new data on its anti-CSF-1R monoclonal antibody, RG7155, at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) 2014. RG7155 is an investigational medicine designed to decrease tumor-associated macrophages, which are induced by cancers to suppress the body’s own anti-cancer immune response. PVNS is a rare, locally aggressive, neoplastic disease of the synovia of large joints. This disorder is mainly driven by accumulation of macrophages; thus, it has been considered as a model disease to prove RG7155 activity. Results will be presented from a phase I dose escalation and extension study with RG7155, which induced objective responses according to RECIST in 83% (15/18) of evaluable patients with advanced PVNS. RG7155 was well tolerated with the majority of adverse events being grade 1 and 2. Data will also be published in the online edition of the journal Cancer cell. Overall, RG7155 was well tolerated with mostly only grade 1 and 2 adverse events (AE). Out of 22 patients already available for the safety analysis, most common AE were asthenia (68%), periorbital and peripheral edema (59% and 45%, respectively) and pruritus (45%). Four patients experienced a serious adverse event (periorbital edema, appendicitis, Lupus erythematosis and erythema) at doses higher than the OBD. RG7155 will be further explored as monotherapy as well as in combination with other therapies including other cancer immunotherapy agents.
