“Based on encouraging efficacy signals and safety data from separate trials exploring the PD-1 inhibitor pembrolizumab (Keytruda) and the PD-L1 inhibitor durvalumab (MEDI4736), there is a role for checkpoint inhibitors in the treatment of glioblastoma multiforme (GBM). Data from the studies were reported by David Reardon, MD, at the 21st Society for Neuro-Oncology (SNO) Annual Scientific Meeting.
“Reardon said that these results mark important firsts in the field: ‘There has been a lot of anticipation regarding the role of checkpoint inhibitors for glioblastoma and whether we’ll see results in any way similar to the exciting results that have been observed in other cancer indications with this new class of cancer therapeutics.’ ”
“Recent research suggests that the presence of PD-L1–positive and CD8+ cells may be useful for predicting responses in patients with non-small cell lung cancer (NSCLC) who have been treated with durvalumab (MEDI4736).
“Sonja Althammer, PhD, presented research on the association between improved survival rates to treatment with durvalumab and high CD8+ and PD-L1+ cell densities during a late-breaking abstract session at the Society for Immunotherapy of Cancer (SITC) 21st Annual Meeting & Associated Programs.”
“A combination of the anti–PD-L1 immune checkpoint inhibitor durvalumab (MEDI4736) with the anti–CTLA-4 monoclonal antibody tremelimumab showed improved tumor response in patients with advanced non–small cell lung cancer (NSCLC) over single-agent therapy.
“The study, published in the Journal for ImmunoTherapy of Cancer, was a phase I, open-label, dose-escalation/expansion study that contained 84 patients. Of these patients, 48 had two or more prior lines of therapy. Data from the study showed improved tumor response regardless of PD-L1 status, with an overall response rate of 25% and 35% of PD-L1-negative patients receiving a response (0% tumor cell staining).”
“AstraZeneca AZN, -0.75% and MedImmune, AstraZeneca’s global biologics research and development arm, today presented encouraging results from their novel combination-focused immuno-oncology portfolio at the American Society of Clinical Oncology (ASCO) Annual Meeting 2015.
“Overall, data indicated clinical activity with manageable safety profiles for the anti-programmed cell death ligand 1 (PD-L1) monoclonal antibody MEDI4736, both as monotherapy and in combination with other immuno-oncology and small molecule therapies across different tumor types and tumor biology.
“MEDI4736 and tremelimumab combination shows clinical activity and tolerability in both PD-L1 positive and PD-L1 negative advanced non-small cell lung cancer (NSCLC) patients; dose confirmed for future studies
“Results from the combination study of MEDI4736 and tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) monoclonal antibody, in the treatment of advanced NSCLC, demonstrated clinical activity in heavily-pretreated patients with a manageable safety profile, establishing appropriate doses to move forward into Phase III combination trials.”
“AstraZeneca and Eli Lilly and Company (Lilly) today announced that they have entered into a clinical trial collaboration to evaluate the safety and preliminary efficacy of AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with ramucirumab (CYRAMZA®), Lilly’s VEGF Receptor 2 antiangiogenic cancer medicine. The planned study will assess the combination as a treatment for patients with advanced solid tumours.
“The Phase I study is expected to establish the safety and a recommended dosing regimen, with the potential to open expansion cohorts in various tumours of interest, for the combination of MEDI4736 and ramucirumab. Under the terms of the agreement, the trial will be sponsored by Lilly. Additional details of the collaboration, including tumour types to be studied and financial terms, were not disclosed.”
It has become routine practice to prescribe targeted drugs to patients with metastatic non-small cell lung cancer (NSCLC), whose tumors harbor molecular alterations in EGFR, ALK, and ROS. However, the majority of patients with NSCLC have no targetable mutations and lack good treatment options. Enter immunotherapy drugs, specifically ‘immune checkpoint blockade antibodies,’ to which many refer simply as ‘anti-PD-1 drugs,’ or simply ‘PD-1 drugs.’ In this post, I provide some updates on the efficacy of anti-PD-1 and anti-PD-L1 drugs in lung cancer. Continue reading…
“A closely watched immune system-boosting drug cocktail from Britain’s AstraZeneca shows promise in advanced lung cancer, despite adverse side effects in a number of patients.
“Researchers said on Wednesday that the combination of the experimental drugs MEDI4736 and tremelimumab had ‘a manageable safety profile with evidence of clinical activity, including in PD-L1 negative disease’.
“The update was provided in a scientific summary, or abstract, released ahead of the annual meeting of the American Society of Clinical Oncology (ASCO) later this month.
“MEDI4736 is an anti-PD-L1 therapy, which works by stopping a tumor’s ability to evade the body’s defenses. Tremelimumab blocks a different molecule, CTLA-4, that also keeps the immune system from attacking cancer.”
“A first-of-its-kind combination of three drugs to treat a deadly form of skin cancer can be taken safely, passing the first hurdle to regulatory approval for a potentially long-lasting treatment.
“The treatment was tested in an early-stage trial that was a collaboration between AstraZeneca Plc and Novartis AG. Researchers combined two drugs, dabrafenib and trametinib — a so-called doublet therapy that has been proven effective in targeting melanomas with mutations in the BRAF gene — with an immune system-based treatment that may prevent the disease from relapsing.
“Dabrafenib, sold as Tafinlar, and trametinib, sold as Mekinist, were developed by GlaxoSmithKline Plc and acquired by Novartis in March. The immune therapy drug, MEDI4736, is being developed by AstraZeneca.
“Melanoma is a rare but deadly form of skin cancer for which a number of drugs have been approved in recent years. Among them are BRAF inhibitors like dabrafenib, which target mutations found in about half of all melanoma patients, as well as immune therapies like Bristol-Myers Squibb Co.’s Yervoy, which unleash the body’s own immune system. Because the immune system can be trained, those therapies may be more durable than other forms of treatment.”
The drugs pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2015, respectively. These two competing blockbuster drugs are already changing the outlook in metastatic melanoma, previously considered to be a fatal disease. Known as ‘immune checkpoint inhibitors,’ they work by releasing ‘brakes’ on a patient’s own immune system, freeing it to attack tumors. In the wake of their success, researchers are now taking immune checkpoint inhibition in new directions. Continue reading…