ArQule, Inc.’s (Nasdaq: ARQL) partner, Basilea Pharmaceutica Ltd. (SIX: BSLN), announced today that it entered into a collaboration with Roche (SIX: RO, ROG) to explore a combination of derazantinib (BAL087) and Roche’s PD-L1-blocking immune-checkpoint inhibitor, atezolizumab (Tecentriq), in patients with urothelial cancer. Basilea expects to start a biomarker-driven multi-cohort phase 1/2 study in mid-2019.
The planned study will assess the safety, tolerability and efficacy of the derazantinib-atezolizumab combination in patients with advanced urothelial cancer and confirmed FGFR genomic aberrations. Basilea will be the sponsor of the study, and Roche will provide clinical supply of atezolizumab.
Peter Lawrence, President and Chief Operating Officer of ArQule, said, “This new combination trial with Tecentriq represents an important step in the development of derazantinib (BAL087, formerly ARQ087) and has the potential to expand meaningfully its therapeutic utility. We look forward to further progress and updates from Basilea.”
Derazantinib was licensed to Basilea Pharmaceutica in April 2018 in the US, EU, Japan and the rest of world excluding Greater China. Under the terms of the license agreement, ArQule is eligible to receive up to $326 million in regulatory and commercial milestone payments.
Derazantinib (BAL087, formerly ARQ 087) is an investigational orally administered small molecule inhibitor of the FGFR family of kinases with strong activity against FGFR1, 2, and 3. Therefore, it is called a panFGFR kinase inhibitor. FGFR kinases are key drivers of cell proliferation, differentiation and migration. FGFR alterations, e.g. gene fusions, overexpression or mutations, have been identified as potentially important therapeutic targets for various cancers, including intrahepatic cholangiocarcinoma (iCCA), urothelial (bladder), breast, gastric and lung cancers.1 Current scientific literature suggests that FGFR alterations exist in a range of 5% to 30% in these cancers.2 In addition, derazantinib inhibits the colony-stimulating-factor-1-receptor kinase (CSF1R). CSF1R-mediated signaling is important for the maintenance of tumor-promoting macrophages and therefore has been identified as a potential target for anti-cancer drugs.3 Moreover, pre-clinical data has shown that tumor macrophage depletion through CSF1R blockade renders tumors more responsive to T-cell checkpoint immunotherapy, including approaches targeting PD-L1/PD-1.3, 4, 5 Basilea in-licensed derazantinib from ArQule Inc. in April 2018. The drug candidate has demonstrated favorable clinical data in previous clinical studies, including a biomarker-driven Phase 1/2 study in iCCA patients.6 Derazantinib has U.S. and EU orphan drug designation for this disease.
Urothelial cancer is the sixth most common cancer in the U.S. These cancers start in the urothelial cells that line the inside of the bladder. 80,000 new cases of bladder cancer have been estimated in the U.S. for 2017. Up to 20 percent of patients will have muscle-invasive disease and present with or will later develop metastases.7 For patients with metastatic disease, outcomes can be poor due to the often rapid progression of the tumor and the lack of efficacious treatments, especially in relapsed or refractory disease.