“Drugmakers including Bristol-Myers Squibb Co and Merck & Co are testing which patients will most benefit from new cancer treatments based on a protein found in their tumors, but that guide, known as a biomarker, may be too unreliable, researchers and health experts said.
“Bristol’s Opdivo and Merck’s Keytruda are both therapies designed to block a protein known as Programmed Death receptor (PD-1) that tumors use to evade the body’s natural defenses. Competitors Roche Holding, AstraZeneca and Pfizer also have similar drugs in an earlier stage of development. The drugmakers are conducting clinical trials that test patient tumors for a related protein called PD-L1.
“The new drugs are mainly aimed at patients with so-called solid tumors suffering from diseases including lung cancer and liver cancer. Lung cancer, the most common type, claims 1.8 million new cases each year worldwide. Sales of drugs to block PD-1 could reach $33 billion a year by 2022, according to Morningstar.”
“Roche (SIX: RO, ROG; OTCQX: RHHBY) will present encouraging results from a Phase Ib study of the investigational cancer immunotherapy atezolizumab (MPDL3280A), in combination with a range of platinum-based chemotherapy combinations commonly used in the treatment of non-small cell lung cancer (NSCLC). The study showed that atezolizumab, a PD-L1 (programmed death ligand-1) inhibitor, shrank tumours (objective response rate; ORR) in 67 percent (20/30) of people with advanced NSCLC when combined with chemotherapy. The addition of atezolizumab to chemotherapy was well tolerated and no unexpected toxicities were reported. The most frequent adverse events (AEs) included those commonly associated with chemotherapy, such as nausea, fatigue and constipation. The data will be presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO).1
” ‘We are encouraged that a high proportion of people responded to combined treatment with atezolizumab (MPDL3280A) and chemotherapy in this early lung cancer study,’ said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. ‘This result indicates that combinations may provide a way to extend the benefits of atezolizumab to a wider range of people, including those with low levels of PD-L1 expression.’
“Roche currently has three ongoing Phase III studies of atezolizumab in combination with chemotherapy in previously untreated advanced NSCLC.”
“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.”
“Chicago May 29 Bristol-Myers Squibb Co’s drug, Opdivo, improved survival for patients with the most common form of lung cancer, nearly doubling survival for those with high levels of a specific protein in their tumors compared with chemotherapy, according to clinical trial results presented on Friday.
“The trial found that Opdivo, part of a new class of drugs that harness the immune system to fight cancer, reduced by 27 percent the risk of death from advanced non-squamous non-small cell lung cancer (NSCLC), compared with chemotherapy. The benefit reached 60 percent for patients with the highest levels of the PD-L1 protein.
“The Bristol drug was approved by U.S. regulators in December to treat advanced melanoma and competes with Keytruda from Merck & Co Inc. Investors have been keeping a close eye on Opdivo’s performance in lung cancer, the most common form of the disease worldwide, and a far larger market. Opdivo was cleared in March to treat the less-common squamous type of NSCLC. Between 85 percent and 90 percent of all lung cancers are NSCLC, and more than two-thirds of those are the non-squamous type, according to the American Cancer Society.”
“A new drug that unleashes the body’s immune system to attack tumors can prolong the lives of people with the most common form of lung cancer, doctors reported on Friday, the latest example of the significant results being achieved by this new class of medicines.
“In a separate study, researchers said they had found that a particular genetic signature in the tumor can help predict which patients could benefit from the immune-boosting drugs.
“The finding could potentially extend use of these drugs to some patients with colorectal cancer, prostate cancer and other tumors that have seemed almost impervious to the new drugs. Most of the substantial results so far with these expensive drugs have been in treating melanoma and lung cancer.
“ ‘If you have the signature, you should treat with these checkpoint inhibitors,’ Dr. Luis A. Diaz Jr., an associate professor of oncology at Johns Hopkins University and the senior author of the study on the genetic marker, said in an interview, referring to the new drugs.”
“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…
“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced interim results from a global, randomised Phase II study (POPLAR) in people with previously treated NSCLC. The study showed the investigational cancer immunotherapy MPDL3280A (anti-PDL1) doubled the likelihood of survival (overall survival [OS]; HR=0.47) in people whose cancer expressed the highest levels of PD-L1 (programmed death ligand-1) compared with docetaxel chemotherapy. An improvement in survival was also observed in people who had medium and high (HR=0.56) or any level of PD-L1 expression (HR=0.63), as characterised by a test being developed by Roche. MPDL3280A was generally well tolerated and adverse events were consistent with what has been previously reported for MPDL3280A in NSCLC. Updated results will be presented in an oral session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO).
“ ‘In our study of MPDL3280A in previously treated lung cancer, the amount of PD-L1 expressed by a person’s cancer correlated with improvement in survival,’ said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. ‘The goal of PD-L1 as a biomarker is to identify people most likely to experience improved overall survival with MPDL3280A alone and which people may be appropriate candidates for a combination of medicines.’ “
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…