Vofatamab shows promise in urothelial cancer
The experimental drug vofatamab, a fibroblast growth factor receptor 3 (FGFR3) targeted antibody, exhibited a favourable safety profile when used alone or in combination with the chemotherapeutic agent docetaxel in patients with metastatic urothelial carcinoma (mUC), according to the results of the FIERCE-21* trial presented at ASCO GU 2019.
This phase 1b/2 study comprised 60 individuals with measurable disease and ECOG** ≤1 who failed prior chemotherapy (including taxanes) or had ≤12 months of (neo)adjuvant chemotherapy. Of these, 19 entered the lead-in phase and received vofatamab 25 mg/kg and docetaxel 75 mg/m2 every 3 weeks. Following this, 42 participants (83 percent male) with FGFR3 mutations/fusions who also failed checkpoint inhibitors entered the expansion phase and were randomized 1:1 to vofatamab monotherapy or to continue with the combination regimen. The treatment regimen was administered on day one of each 21-day cycle. [ASCO GU 2019, abstract 409]
Most treatment-emergent adverse events (TEAEs) were grade 1/2, the most common being asthenia and diarrhoea (21 percent each), followed by decreased appetite and rash (12 percent each). There were no grade 5 events reported, and dose interruptions and reductions were infrequent. There was a low incidence of serious AEs (ie, febrile neutropenia, n=3; combination arm), grade ≥3 TEAEs (six and three in the combination and monotherapy arms, respectively), and treatment discontinuation due to an AE (one in each arm).
Both groups had similar preliminary disease control rates at 6 months (27 percent vs 21 percent for the combination vs monotherapy arms). Only 19 percent of patients continued with the treatment in the monotherapy arm as opposed to 43 percent in the combination arm.
Given evidence showing FGFR3 alterations as oncogenic drivers of bladder cancer, [Mol Cancer Ther 2013;12:1245-1254] FGFR3 inhibitors have the potential to revolutionize the management of mUC in biomarker-selected patients, as well as among those with inadequate response to checkpoint inhibitors, said Dr Andrea Necchi from the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, in a press release.
Given the limited treatment options available, there is a high unmet need for effective and tolerable therapies for patients with advanced mUC who have failed chemotherapy and checkpoint inhibitors, noted Necchi. “[Our findings show that] vofatamab has the potential to be a differentiated FGFR3 inhibitor with a tolerability and activity profile that may provide a much-needed therapeutic option to patients.”
The lack of long-term safety issues may also allow long-term use of vofatamab and docetaxel in this setting, said the researchers. Durability of response and survival rates shall be evaluated on follow-up, they added.
Given the promising combination activity observed with vofatamab, other combinations are also being explored, with a phase 2 study of vofatamab in combination with a checkpoint inhibitor underway, they said.