Clinical Trials

Date: 2016-06-06

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago

Company: Vaximm (Switzerland - Germany)

Product: VXM01

Action mechanism:

• immunotherapy product. VXM01 is an oral T-cell immunotherapy that targets the tumor-specific vasculature and certain immune-suppressive cells. It is based on a live attenuated, safe, orally available, bacterial vaccine strain, which is modified to carry vascular endothelium growth factor receptor-2 (VEGFR2) as the target gene. VXM01 stimulates the patient's immune system to activate VEGFR2-specific, cytotoxic T-cells (so-called killer cells). These immune killer cells then actively destroy cells in the tumor vasculature leading to an increased infiltration of various immune cells into the tumor. In pre-clinical studies, a murine analog VXM01 vaccine showed broad anti-tumor activity in different tumor types. This activity was linked to a VEGFR2-specific T-cell response and was accompanied by the destruction of the tumor vasculature and increased immune cell infiltration. In a double-blind, randomized, placebo-controlled study in 71 patients with advanced pancreatic cancer, VXM01 appeared to be safe and well tolerated and led to the activation of VEGFR2-specific cytotoxic T-cells, which was associated with significantly improved patient survival.

Disease: pancreatic cancer

Therapeutic area: Cancer - Oncology

Country: Germany

Trial details:

• The first clinical study of VXM01 enrolled 45 patients with inoperable pancreatic cancer and primarily tested the safety and tolerability of the oral, VEGFR-2 directed T-cell vaccine. Secondary endpoints of the trial included immunological response, effects on tumor perfusion and other angiogenesis-related biomarkers, clinical responses (RECIST) and overall survival. VXM01-01-DE was designed as a randomized, double-blind, placebo-controlled dose escalation study. Each of the five dose groups consisted of six patients receiving VXM01 and three patients receiving placebo, in addition to gemcitabine as standard of care. Patients were treated with four vaccinations, which were administered during the first seven days. The detailed protocol has been published in BMC Cancer.

Latest news:

• • On June 6, 2016,Vaximm announced that data on its lead product candidate VXM01 in pancreatic cancer were presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois. The poster , entitled, A phase 1 trial extension to assess immunologic efficacy and safety of prime-boost vaccination with VXM01, an oral T cell vaccine against VEGF-receptor 2, in patients with advanced pancreatic cancer (Abstract 3091),discussed findings from a 26-patient study extending the randomized, double-blind, placebo-controlled Phase 1 dose-escalation trial in 45 patients with advanced pancreatic cancer . The purpose of the study extension was to explore if continuous treatments with VXM01 could be safely administered and maintain the increased specific T-cell levels previously observed after VXM01 induction treatment (four administrations within one week). In the extension part of the trial, 26 patients with locally advanced, inoperable, Stage IV pancreatic cancer were treated with either VXM01 (N=18) or a placebo (N=8). Two different doses of VXM01 were tested. Patients received the induction treatment, followed by six monthly treatments beginning on Day 38. All patients were allowed to receive standard of care gemcitabine up to Day 38 and any treatment thereafter.In the study, VEGFR2-specific T-cell responses were detected in a large proportion of the VXM01-treated patients. After the induction period, pronounced (>=grade 2) T-cell responses were observed in about half the patients who received at least one additional administration. In the VXM01 group, specific T-cell responses peaked after three months, with an average four-fold increase compared to baseline; at completion of dosing after six months, these levels were still increased. VXM01 was shown to be generally well tolerated, with some mild to moderate decreases in platelets and lymphocytes and an increase in diarrhea, confirming the findings of the previous studyi. The frequency of drug-related adverse events was comparable after induction treatment and further administrations, indicating that continued dosing with VXM01 did not aggravate the side effect profile of this immunotherapy.While there were no significant differences between placebo and VXM01-treated patients in overall survival, due to the very small number of patients in the study, VXM01-treated patients who responded to vaccination with increased T-cell reactivity towards VEGFR2 showed a significantly improved survival compared to non- or low-grade responders. Notably, all VXM01-treated patients with a grade >=2 response survived the entire vaccination and up to Month 8. In the placebo group and in the previous study with induction treatment only, no association between grade of response and significantly improved survival was found. Dr. Jarl Ulf Jungnelius, Chief Medical Officer at VAXIMM, commented: "The results presented at ASCO demonstrate the importance of continued boost administration of VXM01 to optimize the outcome in patients. We are seeing a relation between increase in overall survival and response to VXM01 on the T-cell level. We plan to further evaluate this innovative oral immunotherapy in a variety of solid tumors. A Phase 2a trial in advanced colorectal cancer is already underway."
• • On February 7, 2013, Vaximm, a Swiss-German biotech company focusing on oral cancer vaccines, has announced topline data from the first clinical trial of its investigational oral cancer vaccine VXM01. The randomized, placebo-controlled, double-blind Phase I/II dose escalation study met all key endpoints and demonstrated safety and tolerability. The study code-named VXM01-01-DE enrolled 45 patients with inoperable pancreatic cancer at the Heidelberg University Hospital (Heidelberg, Germany). In addition to standard-of-care treatment, the patients received several doses of VXM01, a therapeutic vaccine targeting the tumor vasculature, or placebo.
• The results of the study indicate that the vaccine was safe and well tolerated. No dose-limiting toxicities were observed. Besides this primary endpoint, several important secondary endpoints, including specific T-cell response and changes in tumor perfusion, were met. After vaccination with VXM01, a quarter of the patients showed a strongly increased T-cell mediated immune response against the target (VEGFR-2). This effect was distinct from fluctuations observed in the placebo-treated patients. Immunologically responding patients occurred already in the lowest dose group. A third of the VXM01-treated patients had a strong drop in tumor perfusion following the treatment, accompanied by corresponding changes in tumor-specific and angiogenesis-related biomarkers. Tumor perfusion changes in the treatment group were correlated with the VEGFR-2 specific effector and regulatory T-cell responses. More detailed results from the trial will be submitted for presentation at upcoming scientific meetings and for publication in a peer-reviewed journal.
• • On October 22, 2012, Vaximm announced that the companu has completed enrollment in the first clinical trial of its investigational oral therapeutic cancer vaccine VXM01. The randomized, placebo-controlled, double-blind Phase I/II dose escalation study enrolled 45 patients with inoperable pancreatic cancer at the Heidelberg University Hospital (Heidelberg, Germany). In addition to standard-of-care treatment, the patients received several doses of VXM01, a therapeutic cancer vaccine targeting the tumor vasculature. The results of the first, blinded part of the study are expected in the first quarter of 2013.

Is general: Yes