"Preclinical data suggests that combining molecularly targeted agents with immunotherapies such as nivolumab may have synergistic effects and lead to better outcomes for patients," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "This collaboration enables us to study several key compounds, including our new highly-potent ALK inhibitor Zykadia, together with a promising, novel immunotherapy agent, paving the way for potential new treatment approaches for patients with NSCLC."
Both studies will be conducted by Novartis. One trial will evaluate the combination of Opdivo with Zykadia(TM) (ceritinib), an FDA-approved treatment for patients with anaplastic lymphoma kinase-positive (ALK+) metastatic NSCLC who have progressed on or are intolerant to crizotinib. A second study will investigate Opdivo with INC280, a potent and highly selective inhibitor of c-MET receptor tyrosine kinase, and separately with EGF816, a potent, third-generation EGFR tyrosine kinase inhibitor that is active against T790 mutations. INC280 and EGF816 are currently being investigated in various Phase I/II NSCLC trials. Additional details of the collaboration were not disclosed.
This collaboration with Bristol-Myers Squibb further advances Novartis' development efforts in the field of immunotherapy. Earlier this year, Novartis acquired CoStim Pharmaceuticals Inc., adding late discovery stage immunotherapy programs focused on key oncogenic targets, including PD-1. Novartis is also actively investigating the potential of chimeric antigen receptor (CAR) T cell technologies in the treatment of various liquid and solid tumors through its alliance with the University of Pennsylvania.
Zykadia (ceritinib) is indicated in the US for the treatment of patients with ALK+ metastatic NSCLC who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Outside of the US, Zykadia (ceritinib) is an investigational agent and has not been approved by regulatory authorities. Regulatory reviews are currently underway in the European Union and several countries within South America, Central America and Asia.
About INC280 and EGF816
Because these are investigational compounds, the safety and efficacy profiles of INC280 and EGF816 have not yet been established. Access to these investigational compounds is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the treatments. Because of the uncertainty of clinical trials, there is no guarantee that INC280 and EGF816 will ever be commercially available anywhere in the world.
Novartis licensed INC280 from Incyte Corporation and holds exclusive worldwide development and commercialization rights to the compound in all indications.
About Opdivo (nivolumab)
Cancer cells may exploit "regulatory" pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Opdivo is an investigational, fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells.
Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 35 trials - as monotherapy or in combination with other therapies - in which more than 7,000 patients have been enrolled worldwide. Among these are several potentially registrational trials in NSCLC, melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and non-Hodgkin lymphoma. In July, 2014, Opdivo received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma. Opdivo is also under review by the U.S. Food and Drug Administration and European Medicines Agency. Bristol-Myers Squibb has proposed the name Opdivo (pronounced op-dee-voh), which, if approved by health authorities, will serve as the trademark for nivolumab.
Please see full Prescribing Information for Zykadia.
Opdivo® is a registered trademark of Bristol-Myers Squibb Company.
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 135,000 full-time-equivalent associates and sell products in more than 150 countries around the world.
1. Zykadia(TM) (ceritinib) Prescribing Information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; April 2014.