Date: 2017-11-11
Type of
information: Presentation of results at a congress
phase: 1a-1b
Announcement: presentation of results at the Society for Immunotherapy of Cancer (SITC) 32nd Annual Meeting
Company: Five Prime Therapeutics (USA - CA) BMS (USA - NY)
Product: cabiralizumab (FPA008) and nivolumab
Action
mechanism:
- monoclonal antibody/immune checkpoint inhibitor . FPA008 is an antibody that inhibits colony stimulating factor-1 receptor (CSF1R). It blocks the activation and survival of monocytes and macrophages. Inhibition of CSF1R in inflamed RA joints blocks the production of inflammatory cytokines by macrophages and inhibits osteoclasts, monocyte-lineage cells that can cause bone erosions and joint destruction. Inhibition of CSF1R in many cancers reduces the number of immunosuppressive tumor-associated macrophages (TAMs), thereby facilitating an immune response against tumors.
- Opdivo® (nivolumab) is a fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. PD-1, a receptor expressed on the surface of lymphocytes, plays a role in a regulatory pathway that suppresses activated lymphocytes in the body. Available evidence suggests that cancer cells exploit this pathway to escape from immune responses. Opdivo® is thought to provide benefit by blocking PD-1-mediated negative regulation of lymphocytes (i.e., the interaction of PD-1 with its ligands PD-L1 and PD-L2), thereby enhancing the ability of the immune system to recognize cancer cells as foreign and eliminate them. Opdivo® is the world’s first approved drug targeting PD-1. This monoclonal antibody has been generated under a research collaboration entered into in May 2005 between Ono and Medarex. When Medarex was acquired by BMS in 2009, it also granted BMS its rights to develop and commercialize the anti-human PD-1 monoclonal antibody in North America. Through the collaboration agreement entered into in September 2011 between Ono and BMS, Ono granted BMS exclusive rights to develop and commercialize Opdivo® in the rest of the world, except in Japan, Korea and Taiwan where Ono has retained all rights to develop and commercialize the compound.
Disease: advanced solid tumors including pancreatic cancer
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
- The study is a Phase 1a/1b open-label study to evaluate safety, tolerability, pharmacokinetics (PK), and clinical benefit of cabiralizumab in combination with Opdivo® in patients with advanced cancers in single-arm cohorts. In the expansion cohorts, patients received cabiralizumab 4mg/kg plus Opdivo® 3mg/kg intravenous (IV) once every two weeks in a 3+3+3 design. (NCT02526017)
Latest
news:
- • On November 11, 2017, BMS and Five Prime announced preliminary results from a dose escalation and expansion study evaluating the safety, pharmacokinetics and pharmacodynamics of cabiralizumab in combination with Opdivo® (nivolumab) in patients with advanced solid tumors. This is the first disclosure of a clinical experience evaluating an anti-CSF-1 receptor antibody, which depletes immunosuppressive tumor associated macrophages (TAMs), in combination with an anti-PD-1 antibody. Preliminary results show that the safety profile of cabiralizumab plus Opdivo® was generally consistent with that of Opdivo® monotherapy, and that the combination results in dose-related decreases in circulating monocytes. In a cohort of heavily pre-treated patients with advanced pancreatic cancer (n=31 evaluable patients), a patient population that is generally insensitive to immunotherapy, durable clinical benefit was observed in five patients (16%), including confirmed objective responses in three patients with microsatellite-stable (MSS) disease (objective response rate 10%). The data have been presented at the Society for Immunotherapy of Cancer (SITC) 32nd Annual Meeting in a late-breaking oral presentation (abstract #O42).
- More cancer patients are being treated with immunotherapy, but most patients with advanced pancreatic cancer remain resistant to anti-PD-1/PD-L1 therapy and typically have poor outcomes, with an average one-year survival rate of only 16 percent and five-year survival of less than 3 percent. Pancreatic cancer is known to be associated with TAM infiltration and higher TAM infiltration is in turn associated with worse prognosis, suggesting that suppressed immune response contributes to tumor progression in this patient population. These data show for the first time that combining an anti-CSF-1 receptor antibody with Opdivo® may help restore T cell function by a simultaneous reduction of TAMs and inhibition of PD-1 signaling.
- As of data cut-off, 229 patients have been treated, including 205 patients in the combination dose expansion cohorts in advanced solid tumors, of which 33 were pancreatic cancer patients. Cabiralizumab PK activity appears similar as a monotherapy and in combination with Opdivo. The PK of cabiralizumab ? 4 mg/kg Q2W approaches the linear dose range, suggesting saturation of target-mediated clearance. Cabiralizumab alone or in combination with Opdivo results in dose-related decreases in circulating monocytes. Treatment-related adverse events (TRAEs) of any grade occurred in 90 percent (n=184) of patients treated with cabiralizumab and Opdivo, with 49 percent (n=100) of patients experiencing Grade 3/4 adverse events. Of the 24 patients in the monotherapy group, 63 percent (n=15) experienced TRAEs of any grade, and 54 percent (n=13) experienced Grade 3/4 adverse events. The most common TRAEs were elevations in creatine kinase and serum liver enzymes.
- The efficacy data reported at SITC pertain to an expansion cohort in pancreatic cancer. The ongoing Phase 1a/1b trial has started to enroll and treat an additional 30 pancreatic cancer patients to further evaluate the combination in this patient population in a total of 60 patients. Further, BMS is launching a new study of cabiralizumab plus Opdivo® to provide additional insight into the potential benefit of the combination in pancreatic cancer.
Is
general: Yes
