February 8, 2016
By Alex Keown, BioSpace.com Breaking News Staff
LONDON – A new combination cancer treatment of durvalumab and tremelimumab developed by London-based AstraZeneca is showing potential in treating tumors that have not traditionally responded to other immunotherapy treatments, the company announced this morning.
AstraZeneca and its research and development arm MedImmune published data from a Phase Ib study in “The Lancet Oncology” showing the combination treatment was effective in patients with patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) irrespective of PD-L1 status. The data shared is from a small study of only 26 patients, so some caution must be taken when looking at the information. However, the effect of the combination of durvalumab and tremelimumab was more impressive than durvalumab alone. According to the data, the combination of durvalumab and tremelimumab produced a 29 percent response rate from patients with PD-L1 positive and negative tumors, a significant improvement over durvalumab alone, which saw positive responses in 5 percent of patients.
Durvalumab is a monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. The drug has been effective in reversing the ability of some tumors to avoid detection by the immune system. Tremelimumab inhibits the activity of cytotoxic T-lymphocyte-associated antigen-4 (prCTLA-4) to boost the immune response against cancer cells. Preclinical data suggested that targeting both PD-L1 and CTLA-4 may have additive or synergistic effects.
Research has shown that immune checkpoint inhibitors hold promise in treating cancer patients. Many immunotherapies being developed focus on Pd-L1 positive tumors. However, AstraZeneca said less than half of NSCLC patients have tumors that are PD-L1 positive, which leaves a “significant unmet medical need in the PD-L1 negative patient population.” AstraZeneca said the presence of PD-L1 expression in a tumor is considered a significant biomarker for response to PD-L1 blockade.
“The latest findings reinforce our belief that the combination strategy we are pursuing is key to the future success of immuno-oncology treatment,” Ed Bradley, senior vice president of oncology at MedImmune said in a statement.
Despite the positive report of the combination treatment, AstraZeneca’s stock is down more than 5 percent this morning, hitting a morning low of $28.29 per share.
While AstraZeneca is seeing positive results with the combination of durvalumab and tremelimumab in this lung trial, the company halted two clinical trials testing the combination of AZD9291 and durvalumab for lung cancer following reports of patients developing interstitial lung disease-like problems in one trial. The halting of the trials may have stymied some of the momentum AstraZeneca was gaining from AZD9291. In September, AstraZeneca presented data from its AURA Phase I and II studies showing progression free symptoms over a one-year period in 72 percent of patients administered AZD9291 to first-line patients with epidermal growth factor receptor mutation (EGFRm) positive advanced non-small cell lung cancer (NSCLC) and previously treated patients with EGFR T790M mutation-positive NSCLC.
In June, AstraZeneca submitted marketing authorization to the U.S. Food and Drug Administration. Earlier the FDA gave priority review to AZD9291. The drug had already been awarded Breakthrough Therapy designation, Orphan Drug and Fast Track status. Should AZD9291 make it to market, the drug is expected to yield annual revenue of approximately $3 billion.
