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Vintafolide/Docetaxel Shows Promise in Lung Cancer Patients

Combo therapy improves progression-free survival in phase IIb study

A phase IIb clinical trial has met its primary endpoint for the combination of vintafolide and docetaxel (Endocyte, Inc.) in patients with folate receptor-positive recurrent non–small-cell lung cancer (NSCLC).

The data showed that the risk of disease worsening or death was reduced by 25% in patients treated with the vintafolide/docetaxel combination compared with those treated with docetaxel alone (hazard ratio for progression-free survival: 0.75; P = 0.0696).

In the TARGET trial, 199 patients were randomly assigned to one of three treatment arms: vintafolide alone, docetaxel alone, or the vintafolide/docetaxel combination. Secondary endpoints, including the overall response rate and overall survival (OS), also showed trends in favor of the combination arm. Median OS has been reached for the vintafolide and docetaxel single-agent arms but not for the combination-treatment arm. In addition, the combination regimen showed improved activity in patients with adenocarcinoma in a prespecified subset analysis.

The safety profile of the combination arm was consistent with that observed with docetaxel alone and vintafolide alone, although a higher rate of hematologic and peripheral neuropathy adverse events were observed in the combination arm. No drug-related deaths occurred in the combination arm. Single-agent vintafolide at the schedule evaluated in this study demonstrated less activity than single-agent docetaxel.

The international, open-label, phase IIb TARGET trial was designed to evaluate vintafolide in patients with stage IIIb or IV NSCLC who had all lesions positive for the folate receptor, as determined by the investigational companion imaging agent etarfolatide, and who had failed one prior chemotherapy. Secondary endpoints include a comparison of the overall response rate, the disease control rate, the duration of response, the duration of disease control, OS of the participants between treatment arms, and the incidence of adverse and serious adverse events.

The TARGET study included three investigational arms: vintafolide monotherapy and vintafolide in combination with docetaxel, each of which was compared with a standard-of-care control arm, docetaxel monotherapy.

Vintafolide is an investigational conjugate of folic acid (vitamin B9) linked to an anti-cancer agent, the potent vinca alkaloid desacetylvinblastine hydrazide (DAVLBH). Since cancer cells generally consume higher levels of folate than do normal cells to fuel their growth, some cancer cell types — including ovarian and NSCLC — have high concentrations of the folate receptor on their surface. Vintafolide is designed to selectively target the folate receptor to deliver the anti-cancer agent to the cancerous tissue. Tumors that have high concentrations of the folate receptor are identified by etarfolatide, a non-invasive imaging diagnostic agent. Intravenous folic acid is used with technetium (99mTc)-etarfolatide for the enhancement of image quality.

The FDA has granted "orphan drug” status to the combination of vintafolide and etarfolatide. Further evaluation is ongoing in the global phase III PROCEED trial in patients with folate receptor-positive platinum-resistant ovarian cancer. The randomized phase IIb TARGET study of vintafolide in patients with NSCLC has completed enrollment, and a phase II study in patients with triple-negative breast cancer is expected to be initiated in the second quarter of 2014.

Source: Endocyte, Inc.; March 21, 2014.

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