Vx-001 is composed of two separate peptides: the native cryptic peptide ARG-Vx001 (TERT572) and its optimized variant TYR-Vx001 (TERT572Y). Vx-001 has been tested in in vivo experiments in mice, in vitro experiments on human lymphocytes, and a large exploratory Phase I/II clinical trial. Vx-001 vaccination of humanized mice demonstrated protection against tumor growth in vivo (J Clin Invest. 2004 113:425-33). Furthermore, Vx-001 induces anti-tumor immune responses by human lymphocytes in vitro. Vx-001 completed a Phase I/II trial with 33 patients with NSCLC extended to 83 patients with different cancers (mainly breast, prostate and pancreatic cancers) (Oncology .2006;70:306-14, Journal of Clinical Oncology , 2007 19, 2729-34, ASCO 2008 abstract 3030, AACR 2008 abstract 2541, Ann. Oncol., 2012, 23: 442-9, Cancer Immunol. Immunother., 2012, 61: 157-68). The majority of patients (70%) entered the study with progressive disease. Moreover, more than 70% of patients had metastatic disease.
The major conclusions of this Phase I/II trial are the following:
- Vx-001 was safe and well tolerated: only Grade I/II vaccine-related toxicity was observed in vaccinated patients (local skin reaction).
- Vx-001 was strongly immunogenic. Immune responses were observed in the majority of evaluable patients (70%) and appeared as early as after the second vaccination. Long-duration (4-year) immune responses were maintained with vaccination boosts.
- Promising results were obtained in the exploratory analysis of efficacy. One patient (breast cancer) experienced a complete response, three patients (two NSCLC and one HCC) experienced partial responses, and 33 patients demonstrated disease stabilization for more than 6 months. Importantly, clinical outcome correlated with the immune response.
- Analysis of the 33 patients with metastatic NSCLC showed that survival was clearly related to the developed immune response. Immune-responders displayed substantially longer survival than non-immune-responders (24.8 vs 6.9 months).
Vx-001 is being studied in a Phase IIb trial in NSCLC
Vx-001 entered a randomized, placebo controlled, double blind Phase IIb clinical trial in HLA-A*0201 positive patients with TERT expressing NSCLC (stage IV and distant recurrent stage I-III) and controlled disease after first line chemotherapy (NCT01935154) (Clinical Lung Cancer 2013, 14 : 461-5). The primary endpoint is overall survival. Two hundred twenty one patients have been randomized out of 1400 patients screened in more than 70 sites in eight European countries. Results are expected in September 2016.