Novel Immune-Based Cancer Drug Imprime PGG Appears Effective in Certain Lung Cancer Patients

Adding the drug Imprime PGG to chemotherapy and antibody therapy may be effective for certain patients with non-small cell lung cancer (NSCLC). Imprime PGG contains a molecule called beta glucan, which can stimulate the body’s immune cells to destroy cancer cells. This process may be especially effective in patients with high levels of immune system proteins that bind to beta glucan, so-called antibeta glucan antibodies. In a recent clinical trial, patients with advanced NSCLC received the antibody drug cetuximab (Erbitux) and the chemotherapy agents carboplatin (Paraplatin) and paclitaxel (Taxol/Abraxane), and some were also given Imprime PGG. While survival across all patients was not affected by Imprime PGG treatment, it was increased in Imprime PGG-treated patients with high levels of antibeta glucan antibodies. Seventeen percent of these patients survived 3 years or more, while none of the other patient groups did.


Four-Drug Combination Shown to Be Safe and Effective for NSCLC

A combination of the drugs carboplatin (Paraplatin), paclitaxel (Taxol/Abraxane), cetuximab (Erbitux), and bevacizumab (Avastin) has demonstrated effectiveness against non-small cell lung cancer (NSCLC) in a phase II clinical trial. One hundred two patients with advanced non-squamous NSCLC received the four-drug combo as a first-line treatment. Tumors shrank in 56% of patients and stopped growing in an additional 21%. Patients went an average of 7 months without their cancer progressing; the average survival time was 15 months. Four treatment-related deaths occurred, including two due to hemorrhage (heavy bleeding), which can be a rare but serious effect of Avastin treatment. This side effect profile was within the predefined safety margin. A phase III trial further investigating this drug combination for NSCLC is currently enrolling participants.


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.


Phase II Trial of Carboplatin, Paclitaxel, Cetuximab, and Bevacizumab Followed by Cetuximab and Bevacizumab in Advanced Nonsquamous Non-Small-Cell Lung Cancer: SWOG S0536

Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC.

 

This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819.


Tumor-Specific Activation of an EGFR-Targeting Probody Enhances Therapeutic Index

Target-mediated toxicity constitutes a major limitation for the development of therapeutic antibodies. To redirect the activity of antibodies recognizing widely distributed targets to the site of disease, we have applied a prodrug strategy to create an epidermal growth factor receptor (EGFR)–directed Probody therapeutic—an antibody that remains masked against antigen binding until activated locally by proteases commonly active in the tumor microenvironment. In vitro, the masked Probody showed diminished antigen binding and cell-based activities, but when activated by appropriate proteases, it regained full activity compared to the parental anti-EGFR antibody cetuximab. In vivo, the Probody was largely inert in the systemic circulation of mice, but was activated within tumor tissue and showed antitumor efficacy that was similar to that of cetuximab.


Safer, Peptide-Based Therapies Studied as Alternative to Monoclonal Antibodies

Monoclonal antibodies and small-molecule inhibitors have been the primary treatment methods for many types of cancer for many years, but new studies may change that. Peptides, proteins made of small chains of 10 to 50 amino acids, are being examined as possible cost-effective, more successful, safer anticancer vaccines. Researchers have identified two regions on the HER1 (also known as the EGFR) protein as possible targets for these peptide-based drugs. These agents could be used in the treatment of lung cancer, breast cancer, colorectal cancer, and head and neck cancers. If successful, the EGFR-targeting peptide vaccines could be combined with immunotherapies for the HER2 and VEGF proteins, possibly reducing the likelihood that the cancer will develop resistance to the treatment, a common pitfall of monoclonal antibody drugs such as cetuximab (Erbitux).


Evidence of Epidermal Growth Factor Receptor Expression in Uveal Melanoma: Inhibition of Epidermal Growth Factor-Mediated Signalling by Gefitinib and Cetuximab Triggered Antibody-Dependent Cellular…

“Despite advances in surgery and radiotherapy of uveal melanoma (UM), many patients develop distant metastases that poorly respond to therapy. Improved therapies for the metastatic disease are therefore urgently needed. Expression of the epidermal growth factor receptor (EGFR), a target of kinase inhibitors and humanised antibodies in use for several cancers, had been reported. Forty-eight human UMs were analysed by expression profiling. Signalling was tested in three EGFR expressing UM cell lines by Western blotting using phosphorylation specific antibodies for EGFR and the downstream mediators AKT (v-akt murine thymoma viral oncogene homolog) and extracellular signal-regulated kinase (ERK). Evidence for signalling in tumours was obtained through the application of a UM-specific EGF-signature. The EGFR specific kinase inhibitor, Gefitinib and the humanised monoclonal antibody, Cetuximab, were tested for their effect on EGFR signalling. Natural killer cell mediated antibody-dependent cellular cytotoxicity (ADCC) and tumour necrosis factor α (TNF-α) release was analysed for Cetuximab.”


Standard-Dose Radiation Therapy Safer and More Effective Than High-Dose Therapy in Stage III NSCLC

Standard-dose radiation therapy gives better results compared to high-dose radiation in patients with locally advanced stage III non-small cell lung cancer (NSCLC), a recent clinical trial showed. Patients treated with 60 Gy of radiation had longer median survival (28.7 vs 19.5 months) and higher 18-month survival rates (66.9% vs 53.9%) compared to those receiving 74 Gy of radiation. Standard-dose therapy resulted in less cancer spread, lower rates of recurrence, and fewer severe side effects and treatment-related deaths than high-dose radiation. All patients also received chemotherapy with or without cetuximab (Erbitux) in addition to radiation; a future analysis will look at whether Erbitux helped survival.


Phase II Trial of Lung Cancer Drug Imprime PGG Completes Patient Enrollment

Biothera has completed patient enrollment in a second phase II clinical trial testing a drug called Imprime PGG against non-small cell lung cancer (NSCLC). Imprime PGG redirects the immune system to attack the cancer. The drug also enhances the effectiveness of antibody drugs (drugs in the form of a type of immune system protein) like bevacizumab (Avastin) or cetuximab (Erbitux). The current phase II trial will compare NSCLC patients receiving Imprime PGG in combination with Avastin and chemotherapy to those receiving only Avastin and chemotherapy. Another ongoing phase II trial uses a similar design, but with Erbitux instead of Avastin, and has produced promising preliminary results.