Clinical Trials

Date: 2015-09-07

Type of information: Presentation of results at a congress

phase: 2b

Announcement: presentation of results at the World Conference on Lung Cancer

Company: Endocyte (USA - IN)

Product: vintafolide

Action mechanism:

• 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 normal cells to fuel their growth, some cancer cell types - including 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.

   

Disease: folate receptor (FR) positive recurrent non-small cell lung cancer (NSCLC)

Therapeutic area: Cancer - Oncology

Country:

Trial details:

• TARGET is an international, multicenter, open-label Phase 2b study designed to evaluate vintafolide in patients with stage IIIb or IV NSCLC with all lesions positive for the folate receptor [FR(100%)] as determined by the investigational companion imaging agent etarfolatide (EC20) and who have failed one prior chemotherapy  The trial was conducted in 199 patients. The primary endpoint was an improvement in PFS and secondary endpoints include the comparison of overall response rate, disease control rate, duration of response, duration of disease control, overall survival of the participants between treatment arms, and the incidence of adverse and serious adverse events. TARGET included three investigational arms, vintafolide monotherapy and vintafolide in combination with docetaxel, each of which was compared to a standard-of-care control arm, docetaxel monotherapy. (NCT01577654).

Latest news:

• • On September 7, 2015, Endocyte presented the final overall survival (OS) analysis from the Phase 2b TARGET trial evaluatin vintafolide in combination with docetaxel in patients with FR positive recurrent NSCLC at the World Conference on Lung Cancer in Denver, Colorado.
• Vintafolide plus docetaxel improved overall survival by 2.7 months in NSCLC regardless of histology (Median OS 11.5 vs. 8.8 months, OS HR=0.86, 95% CI [0.58, 1.26]). In the predefined subset analysis of patients with adenocarcinoma, which expresses higher levels of folate receptor, vintafolide plus docetaxel improved OS by 5.9 months (12.5 vs. 6.6 months, HR=0.72, 95% CI [0.44, 1.16]). OS for vintafolide as single agent was similar to docetaxel (OS 8.4 vs. 8.8 months, HR=1.02, 95% CI [0.70, 1.50]).
• The study previously reported that the PFS primary endpoint was met, (HR=0.75, 95% CI [0.52, 1.09]) regardless of histology and in the adenocarcinoma subgroup (HR=0.73, 95% CI [0.46, 1.16]). The safety profile of the combination arm was consistent with those observed with docetaxel alone and vintafolide alone, though a higher rate of hematologic and peripheral neuropathy adverse events were observed in the combination arm.
• • On September 27, 2014, Endocyte announced that vintafolide in combination with docetaxel extended overall survival (OS) for patients with folate receptor (FR) positive recurrent non-small cell lung cancer (NSCLC) compared to patients receiving monotherapy docetaxel in its TARGET Phase 2b clinical trial. The late-breaking TARGET trial data have been presented at the European Society for Medical Oncology Congress (ESMO), by Rohit Lal, M.D., consultant medical oncologist at Guys and St Thomas' Hospital and an Honorary Consultant Medical Oncologist for Kings College Hospital, London.
• The data show that patients in the predefined adenocarcinoma subgroup treated with the vintafolide plus docetaxel combination had a 27 percent reduction in risk of the disease worsening or death (HR=0.73, p=0.0899, one-sided test), and a 30 percent reduction in the risk of death (HR=0.70, p=0.1018) compared to docetaxel monotherapy. Stratified analysis, which adjusts for pre-defined patient characteristics in the trial, reflect a 49 percent reduction in the risk of death in patients with adenocarcinoma (HR=0.51, p=0.0147). These data include approximately 78 percent of the targeted number of events in the overall survival analysis. Overall survival in all patients, including those with squamous disease, reflect a 12 percent reduction in the risk of death (HR=0.88, p=0.2874) or 25 percent reduction when stratified (HR=0.75, p=0.1066). The primary endpoint of the study, as presented previously, showed that risk of disease worsening or death (progression-free survival, or PFS) was reduced by 25 percent for patients who received vintafolide plus docetaxel (HR=0.75, p=0.0696).
• The study enrolled and treated 199 patients whose target tumors were all positive for the folate receptor, as determined with the companion imaging agent etarfolatide. Patients were randomized between three arms: vintafolide monotherapy, a combination of vintafolide and docetaxel, and docetaxel monotherapy. The independent data safety monitoring board determined before the completion of the trial that the vintafolide monotherapy arm was not likely to demonstrate increased benefit in the delay of disease progression compared to docetaxel alone.

Patients with recurrent folate-receptor positive adenocarcinoma NSCLC
		Vintafolide +
		Docetaxel	Docetaxel
	Comparison*	(N=43)	(N=49)
Overall response rate	6.6% difference	20.90%	14.30%
Median progression free survival	1.2 month difference	4.2 months	3.0 months
Unstratified analysis	HR=0.73, p=0.0899
Stratified analysis	HR=0.68, p=0.0732
Median overall survival	5.9 month difference,	12.5 months	6.6 months
Unstratified analysis	HR=0.70, p=0.1018
Stratified analysis	HR=0.51, p=0.0147
* One-side p-value

• The most common ( > 5 percent incidence) Grade 3 or higher adverse events occurring more frequently in the vintafolide plus docetaxel arm compared to docetaxel monotherapy were neutropenia (72 percent vs. 55 percent), febrile neutropenia (14 percent vs. 6 percent), sepsis/neutropenic sepsis (6 percent vs. 2 percent), and peripheral neuropathy (9 percent vs. 0 percent).

Is general: Yes