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Positive Results Reported for Targeted Immunotherapy in Lung Cancer Patients

Investigators evaluate recombinant vaccinia virus

Promising results have been reported from the phase IIb part of the phase IIb/III TIME study of investigational mucin 1 (MUC1)–targeted immunotherapy (TG4010, Transgene SA) in patients with advanced non–small-cell lung cancer (NSCLC).

After an updated analysis, the primary endpoint of progression-free survival (PFS) to validate the triple-positive activated lymphocyte (TrPAL) predictive biomarker was met in the normal TrPAL group. The high TrPAL group had not yet met the required number of events to conduct the primary analysis.

Importantly, in a subgroup of patients with a non-squamous histology — most of the patients in the trial (191/217) — the difference in PFS was statistically significant between TG4010 and placebo (hazard ratio [HR], 0.71; P = 0.02). As expected, in this non-squamous population, the PFS HR was greater in the normal TrPAL subgroup.

To date, more than 350 patients have been treated with TG4010. The TIME trial is a randomized, placebo-controlled study evaluating TG4010 in combination with chemotherapy compared with placebo plus chemotherapy in the first-line treatment of MUC1-positive patients with advanced NSCLC.

TG4010 is a recombinant vaccinia virus of the Ankara strain (MVA) expressing the coding sequences of the MUC1 antigen and of the cytokine interleukin-2. In healthy cells, the MUC1 protein is normally found on the surface of epithelial cells in many types of tissue and works to protect these cells.

In tumor cells, several modifications of MUC1 can occur: over-expression, hypo-glycosylation, and changes in cellular localization. These changes transform the MUC1 cell-surface protein into a highly immunogenic tumor-associated antigen and make it an attractive target for cancer immunotherapy. Therefore, the strategy is to induce MUC1 antigen expression in a non-tumor environment (i.e., where the immune system is fully functional) to induce both innate and MUC1-specific adaptive immunity.

In addition to NSCLC, the MUC1 tumor-associated antigen is expressed in many other solid tumor types, such as lung, breast, colorectal, kidney, and prostate cancers. TG4010 is also being studied in preclinical tests in combination with immune checkpoint inhibitors.

Lung cancer is one of the most common malignancies worldwide, with an estimated incidence of 1.6 million people, and is the leading cause of cancer-related deaths, accounting for an estimated 1.4 million deaths in 2008, the latest figures available. NSCLC represents approximately 80% of all lung cancers.

In the U.S., deaths due to lung cancer were expected to account for approximately 27% of all cancer deaths in 2013 — more than from colon, breast, and prostate cancers combined. It was estimated that more than 228,000 new cases of lung cancer would be diagnosed in the U.S. in 2013 and that more than 159,000 disease-related deaths would occur. Lung cancer remains one of the cancer types with the worst prognosis. The 5-year survival rate for NSCLC is 18% in the U.S.

Current treatments for lung cancer include surgery, chemotherapy, radiation, and targeted molecular therapy, but only one-third of patients present with resectable disease at diagnosis. The poor prognosis in patients with advanced disease is improved by platinum-based chemotherapies, which produce longer survival times. However, the medical need for new treatments for NSCLC remains high.

Source: Transgene; May 27, 2014.

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