An early clinical trial of the drug MK-3475 in non-small cell lung cancer (NSCLC) has yielded promising results. MK-3475 targets PD-1, a protein on the surface of immune cells. Another protein, PD-L1, is present on many tumor cells and can bind to PD-1, which deactivates immune cells. MK-3475 blocks PD-1, allowing the immune cells to keep attacking cancer cells. Patients with advanced NSCLC who had failed at least two other treatments were given MK-3475. Tumors shrank in 24% of the patients overall. However, tumor shrinkage occurred in 67% of patients with high levels of PD-L1 on their tumors, compared to only 9% of others. PD-L1 levels may therefore help predict which patients will likely respond to MK-3475.
A new clinical trial will investigate the safety of vantictumab (OMP-18R5), a new lung cancer drug targeting cancer stem cells (CSCs). CSCs, the actively multiplying cells responsible for generating tumors, are thought to be central in cancer relapse by ‘repopulating’ tumors, even if the bulk of the tumors cells are destroyed during treatment. Vantictumab blocks the Wnt pathway, a key molecular signaling pathway used by CSCs. Patients with previously treated advanced non-small cell lung cancer (NSCLC) will receive vantictumab in combination with the chemotherapy agent docetaxel (Taxotere). In addition to the safety of the drug combination, the trial will also investigate how effective it is and whether any biomarkers predict how well patients respond.
While medical research has produced significant treatment innovations for many cancer types, so far little has changed for small cell lung cancer (SCLC). Current treatment guidelines recommend chemotherapy with etoposide (Etopophos) and cisplatin (Platinol), drugs than are more than 30 years old. Relapse is common, and survival rates remain low. Now, the new PINNACLE clinical trial will investigate a new drug against SCLC. Patients with extensive-stage SCLC who have never received any other cancer treatment will be treated with Etopophos and Platinol either by themselves or in combination with the new drug, OMP-59R5. The drug acts by inhibiting NOTCH, a protein involved in cell development and growth that plays a role in various cancers. For more information, call 646-888-4203.
A phase I clinical trial marks the start of early testing for new cancer drug IMGN289. IMGN289 is a so-called antibody-drug conjugate (ADC). ADCs combine antibodies (immune system proteins designed to bind to specific targets) with chemotherapy drugs to help steer the chemotherapy agents specifically towards tumors and spare healthy tissues. IMGN289 consists of an antibody that binds to EGFR, a protein expressed in many lung cancer tumors, connected to a cell-killing agent called DM1. The trial will study patients with non-small cell lung cancer (NSCLC) and other cancers that express high levels of EGFR. After determining the highest IMGN289 dose that can safely be administered to patients, the study will evaluate the effectiveness of the drug in different patient subgroups.
Three new immunotherapy drugs for non-small cell lung cancer (NSCLC) – nivolumab, lambrolizumab (MK-3475), and MPDL-3280A – have produced encouraging early results. All three interfere with PD-1 and PD-L1, molecules that interact to shield tumors from being attacked by the body’s immune system. In phase I trials, more than 20% of participants experienced tumor shrinkage in response to each of the three drugs. For these patients, effects tended to be rapid and long-lasting. Most continue to respond favorably to treatment at this time, having been in the trials for up to 7 months (MPDL-3280A), an average of 9 months (lambrolizumab), or an average of 1.5 years and ranging up to 2.5 years (nivolumab). Overall toxicity was acceptable, though some cases of severe side effects were seen, including two deaths with nivolumab.
Results from an early clinical trial suggest that the drug MPDL3280A is effective against non-small cell lung cancer (NSCLC). The phase I study found that tumors shrank in 23% of patients with advanced NSCLC treated with MPDL3280A. The effect was more pronounced in smokers (who had a 26% response rate) than in nonsmokers (a 10% rate), making it the first treatment with stronger activity in smokers. MPDL3280A inhibits PD-L1, a protein expressed on cancer cells that suppresses the immune response. Blocking PD-L1 allows the immune system to keep attacking the cancer. The tumor cells in smokers may carry more mutations, provoking a stronger attack from the unleashed immune system, which could explain the stronger effects in smokers.
Mesothelioma is a form of lung cancer strongly associated with exposure to asbestos. Even though asbestos has been banned or heavily regulated in most developed nations, due to delayed onset, the number of mesothelioma cases is predicted to climb until around 2020. In the UK, which has the highest mesothelioma incidence worldwide, two new clinical trials are aiming to find treatments for the disease. The Meso2 trial will investigate ganetespib, while the COMMAND trial will examine defactinib. Defactinib specifically targets cancer stem cells, which often survive cancer treatment and cause cancer recurrence. The drug may therefore help prevent relapse after first-line therapy.
The Novartis second-generation ALK inhibitor LDK378 showed an overall response rate of 60% in a phase I trial involving 130 patients with ALK-positive non–small cell lung cancer. Both patients who had never received a targeted therapy and those who had become resistant to crizotinib responded to the drug.