September 26, 2018 Positive results from the 6-months Interim analysis of the phase IIa clinical study in high grade cervical dysplasia provides Proof-of-Concept for Vaccibody’s immunotherapy platform.
Vaccibody AS today announced positive 6-months interim results from the phase IIa part of the clinical study VB C-01. This study is a first human dose, open-label, multicenter phase I/IIa study of VB10.16 immunotherapy for the treatment of high grade Cervical Intraepithelial Neoplasia (CIN 2/3) caused by human papillomavirus 16 (HPV16). 12-months data will be announced in Q1, 2019.
The phase IIa enrolled 18 CIN 2/3 patients, 1 patient was withdrawn and 17 patients each received four doses of 3 mg of VB10.16 at week 0, 3, 6 and 16 weeks. The primary objective of the study was to evaluate the safety and tolerability of VB10.16. The secondary objectives were to assess T cell mediated immune responses in the peripheral blood and to evaluate early signs of efficacy by means of CIN regression and HPV clearance. The vaccine was delivered with a pain-less PharmaJet® Stratis Needle-free Injection System.
The treatment with the four doses of VB10.16 was well tolerated in the phase IIa part as it was in the phase I part of the study. No serious adverse advents (SAEs) or unexpected adverse events were reported. The most frequently reported AEs were transient mild to moderate reactions at the injection site.
Immunological analyses of the peripheral blood demonstrated a strong HPV16-specific T cell immune response in 17 of 17 patients evaluated. The response was induced by the vaccine in 16 of 17 patients against both antigens used in the vaccine (HPV16 proteins E6 and E7). One patient had a strong baseline response and thus was not further induced by the vaccine. These results constitute a proof-of-concept for the Vaccibody DNA vaccine technology delivered by jet injection regarding its ability to generate a rapid, strong and long-lasting response.
One patient had conization at 4 months and could not be assessed at 6 months. Of the remaining 16 patients, 15 patients showed a partial or complete response at 6 months (13 partial responders, 2 complete responders, 1 stable disease). 14 patients showed a reduction in lesion size from colposcopic examination at 6 months (median reduction for these 14 patients was 50%). Histopathological regression to low grade neoplasia (CIN 1) or no disease was seen in 8 patients. Of the 8 patients that have not regressed to CIN1 or less at 6 months, 6 patients showed upregulation of PD-L1 in the lesions which may delay or inhibit elimination of all affected cells. Three of these patients had also persistent co-infection with other high-risk HPV strains, including one patient which had cleared HPV16.
Adding a 4th vaccination at 4 months significantly boosted the T cell response and the strongest response was observed at 6 months. Change in lesion size and CIN regression will be monitored until 12 months after first vaccination.
Martin Bonde, CEO of Vaccibody, commented: We are very pleased with the data we have seen so far. The vaccine has an excellent safety profile and the T cell immune responses observed indicate that VB10.16 induces a stronger HPV16-specific immune response than what we have seen reported in the literature and the 4th dose significantly boosts and thus prolongs the T cell response where we observe the strongest response at 6 months (at the time of this interim analysis). While other DNA vaccines developed for this indication require delivery with in vivo electroporation, which requires more investment in equipment and is reported to be quite painful, VB10.16 is delivered by a simple needle-free, painless jet injection which we believe improves patient compliance tremendously and will be a significant asset in further development of this product. The fact that we see a high response rate, with significant lesion size reduction shows that most patients truly benefit from the strong T cell response induced by VB10.16 monotherapy. Moreover, we observe CIN regression in a high percentage of these patients at 6 months. The fact that we observe PD-L1 upregulation in response to vaccination in the patients that do not have CIN regression before 6 months, substantiates the mechanism of action of the vaccine and invites to pursue potential synergistic effects by combining therapeutic Vaccibody cancer vaccines and checkpoint inhibitors, like we have observed in preclinical experiments. We are currently exploring opportunities for the combination of the VB10.16 vaccine with a checkpoint inhibitor in order to treat established HPV16+ cervical cancer, head and neck cancer, anal cancers and other HPV16+ cancers.
The VB C-01 is the first clinical study utilizing Vaccibody’s Vaccine Platform Technology and the positive results can have a significant impact not only on the development of the company’s lead product, VB10.16, but very importantly also represent a proof of principle for the technology and the potential to use this platform in further indications. One such example is our cancer neoantigen study VB N-01 in patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma , urothelial cancer or squamous cell carcinoma of the head and neck.
The company’s first product, VB10.16, is a therapeutic DNA vaccine developed to treat human papillomavirus type 16 (HPV16) induced pre-malignancies and malignancies.
About Cervical Intraepithelial Neoplasia (CIN) and Cervical Cancer
Per year, approximately 530,000 women are diagnosed with cervical cancer worldwide and over 275,000 women die of the disease annually. Invasive cervical cancer is preceded by a long phase of pre-invasive disease called Cervical Intraepithelial Neoplasia (CIN). Globally the number of high grade lesions (CIN 2/3), the immediate precursors to malignancy, is estimated to be in the range of 10 million.
Virtually all cervical cancers are caused by high risk HPV types. Among the different high risk HPV types known, HPV16 has been reported to be the most common genotype in high grade cervical intraepithelial neoplasia. It can be detected in up to 60 % of all cervical cancers, especially in younger women and it has also been found to play an essential role in the development of several other cancer types (approximately 90% of anal cancers; 40% of penile, vaginal, and vulvar cancers; 25% of oral cavity cancers and 35% of oropharyngeal cancers).
Current standard therapy for CIN 2/3 varies between countries and regions and often involves surgical removal of the affected tissue. These invasive procedures are associated with bleeding, infection, cervical stenosis, scarring and most importantly pre-term deliveries in subsequent pregnancies. As a result, there is a significant need for an effective therapeutic vaccine to treat existing HPV infection and associated pre-malignancies and malignancies of the cervix and thereby prevent the development of cervical cancer caused by human papillomavirus.
About Vaccibody AS
Vaccibody is a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel immunotherapies. The company is a leader in the rapidly developing field of individualized cancer neoantigen vaccines and is using the Vaccibody technology to generate best-in-class therapeutics to treat cancers with a high unmet medical need. A phase I/IIa neoantigen clinical trial is now enrolling patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell carcinoma of the head and neck. Vaccibody’s front runner program (VB10.16) is a therapeutic DNA vaccine against HPV16 induced pre-malignancies and malignancies. The first-in-human study (phase I/IIa), which is now fully enrolled, evaluates the safety and immunogenicity of VB10.16 in women with high grade cervical intraepithelial neoplasia (HSIL; CIN 2/3).
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