ASCO: Nivolumab Treatment in Melanoma Patients Has Manageable Safety Profile

“The monoclonal antibody nivolumab has shown promise as a therapeutic agent, particularly by improving the survival rates of melanoma patients. Jeffrey S. Weber, M.D., Ph.D., director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt Cancer Center will be presenting data from a retrospective analysis of the safety of nivolumab in 4 ongoing phase I-III studies in melanoma patients at the 2015 American Society of Clinical Oncology Annual Meeting in Chicago.

“Nivolumab targets a protein called the programmed death-1 (PD-1) receptor. The PD-1 pathway plays an important role in controlling the immune system to prevent inadvertent immune cell activation and autoimmune disease. PD-1 is found on immune cells called T cells, while its ligand PD-L1 is expressed on antigen presenting cells. Binding of PD-L1 to PD-1 inhibits the replication and activity of immune cells and prevents an immune response. Melanoma cells express high levels of PD-L1 to avoid immune detection and improve their survival potential.”


ASCO: Antibody Adds 6 Weeks to Squamous NSCLC Survival

“The novel anti-EGFR monoclonal antibody necitumumab modestly improved survival in squamous non-small cell lung cancer (NSCLC) in a pivotal trial, but many called the effect too small to count.

“Adding the drug to a standard chemotherapy regimen improved overall survival by 16% (P=0.012), Nick Thatcher, MD, of Christie Hospital in Manchester, England, and colleagues found in the SQUIRE trial.

“While only about a 6-week gain over chemotherapy alone (median 11.5 versus 9.9 months), Thatcher called the findings an important advance.”

Editor’s note: Necitumumab is a drug that may hold promise for some patients with squamous non-small cell lung cancer (NSCLC). In a clinical trial to test the drug on volunteer patients, researchers found that necitumumab can increase survival by 6 weeks, compared to standard chemotherapy treatment. Some researchers say a 6 week increase in survival time is not terribly meaningful, and may be setting the bar too low for treatment of squamous NSCLC.


New Cancer Vaccine Approach Directly Targets Dendritic Cells

“Celldex Therapeutics announced today that final data from its Phase 1 study of CDX-1401 in solid tumors, including long-term patient follow-up, have been published inScience Translational Medicine. The data demonstrate robust antibody and T cell responses and evidence of clinical benefit in patients with very advanced cancers and suggest that CDX-1401 may predispose patients to better outcomes on subsequent therapy with checkpoint inhibitors. CDX-1401 is an off-the-shelf vaccine consisting of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC-205 linked to the NY-ESO-1 tumor antigen. The vaccine is designed to activate the patient’s immune system against cancers that express the tumor marker NY-ESO-1. While the function of NY-ESO-1 continues to be explored, references in the literature suggest that its expression might reflect the acquisition of properties that cancers find useful, such as immortality, self-renewal, migratory ability and the capacity to invade.”

Editor’s note: Cancer vaccines like CDX-1401 are a type of immunotherapy, meaning that they boost a patient’s own immune system to fight cancer. CDX-1401 is able to attack tumor cells because the tumor cells have a molecule called NY-ESO-1 that CDX-1401 recognizes. We recently published a story about another treatment that is meant for patients whose tumors have NY-ESO-1. To learn more about how patients can use molecular testing to see if particular treatments might work for them, click here.


New Cancer Vaccine Approach Directly Targets Dendritic Cells

“Celldex Therapeutics announced today that final data from its Phase 1 study of CDX-1401 in solid tumors, including long-term patient follow-up, have been published inScience Translational Medicine. The data demonstrate robust antibody and T cell responses and evidence of clinical benefit in patients with very advanced cancers and suggest that CDX-1401 may predispose patients to better outcomes on subsequent therapy with checkpoint inhibitors. CDX-1401 is an off-the-shelf vaccine consisting of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC-205 linked to the NY-ESO-1 tumor antigen. The vaccine is designed to activate the patient’s immune system against cancers that express the tumor marker NY-ESO-1. While the function of NY-ESO-1 continues to be explored, references in the literature suggest that its expression might reflect the acquisition of properties that cancers find useful, such as immortality, self-renewal, migratory ability and the capacity to invade.”

Editor’s note: Cancer vaccines like CDX-1401 are a type of immunotherapy, meaning that they boost a patient’s own immune system to fight cancer. CDX-1401 is able to attack tumor cells because the tumor cells have a molecule called NY-ESO-1 that CDX-1401 recognizes. We recently published a story about another treatment that is meant for patients whose tumors have NY-ESO-1. To learn more about how patients can use molecular testing to see if particular treatments might work for them, click here.


Erbitux-Avastin Combination Plus Chemotherapy in Lung Cancer Is Safe and Effective

Combining cetuximab (Erbitux), bevacizumab (Avastin), and traditional chemotherapy in patients with non-small cell lung cancer (NSCLC) appeared to be safe and effective in a phase II clinical trial. Patients with advanced non-squamous NSCLC received Erbitux and Avastin in addition to carboplatin (Paraplatin) and paclitaxel (Taxol/Abraxane) as first-line treatment, followed by maintenance treatment with Erbitux and Avastin. Tumors shrank in 56% of patients and stopped growing in an additional 21%. Serious side effects were relatively rare; the rate was comparable to that of either Erbitux or Avastin alone. Both Erbitux and Avastin have shown efficacy in NSCLC by themselves, but may be more effective when given together. An ongoing phase III clinical trial will further investigate this drug combination.


Effect of New Lung Cancer Drug Depends on MET Protein Expression Levels

The cell protein MET is overexpressed in more than half of non-small cell lung cancer (NSCLC) tumors. MET overexpression is associated with worse prognoses and plays a role in drug resistance to EGFR inhibitors like erlotinib (Tarceva). A recent clinical trial examined the effects of onartuzumab, which inhibits MET function, on recurrent NSCLC. Patients received either onartuzumab and Tarceva or Tarceva only. In patients who overexpressed MET, adding onartuzumab increased the time until cancer progression and prolonged overall survival. In contrast, in patients without MET overexpression, adding onartuzumab worsened outcomes. This finding highlights the importance of diagnostic testing in choosing the best cancer treatment. A clinical trial investigating the onartuzumab-Tarceva combination in MET-overexpressing patients only is currently enrolling participants.


Novel Anti-PD-L1 Antibody Achieves Durable Responses in Phase I Study of Patients With Metastatic NSCLC, Smokers Included

For the first time, an immunotherapy shows promise in smokers with non–small cell lung cancer (NSCLC). The engineered monoclonal antibody MPDL3280A achieved encouraging and durable responses in a phase I study in metastatic NSCLC in smokers and nonsmokers, and with squamous and adenocarcinoma histology. Responses were more robust in smokers than nonsmokers, which is not what usually happens in drug trials of NSCLC, explained lead author Jean-Charles Soria, MD, of Institut Gustave Roussy, Paris, at the European Cancer Congress 2013 in Amsterdam.


Tremelimumab for Patients with Chemotherapy-Resistant Advanced Malignant Mesothelioma: An Open-Label, Single-Arm, Phase 2 Trial

Monoclonal antibodies to cytotoxic T-lymphocyte antigen 4 (CTLA4) have therapeutic activity in different tumour types. We aimed to investigate the efficacy, safety, and immunological activity of the anti-CTLA4 monoclonal antibody, tremelimumab, in advanced malignant mesothelioma.

Although the effect size was small in our phase 2 trial, tremelimumab seemed to have encouraging clinical activity and an acceptable safety and tolerability profile in previously treated patients with advanced malignant mesothelioma.


EGFR Antibody Increases Survival in Lung Cancer Trial

The new cancer drug necitumumab increased survival in the SQUIRE clinical trial, a phase III trial examining squamous non-small cell lung cancer (NSCLC).  Patients with stage IV squamous NSCLC who received necitumumab in addition to the chemotherapy agents cisplatin (Platinol) and gemcitabine (Gemzar) survived longer than those treated with chemotherapy alone. Necitumumab is an antibody (a type of immune system protein) that blocks the function of EGFR, a protein that plays an important role in the survival, spread, and blood supply of tumors.