NCT03715985

Personalized Neo-antigen Vaccine in Advanced Solid Tumors (NeoPepVac)

A Pilot Study of the Safety, Tolerability, Feasibility and Efficacy of Anti-PD-1 or Anti-PD-L1 in Combination With a Personalized Neo-antigen Vaccine in Advanced Solid Tumors (NeoPepVac)

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Herlev Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

The primary objective is to assess tolerability and safety of a personalized neo-antigen vaccine containing up to 15 peptides derived from somatic mutation of the individual patient's cancer, with CAF09b as adjuvant. The vaccine formulation will be administered in combination with an approved anti-PD-1 or anti-PD-L1 inhibitor to patients with advanced solid tumors. The endpoint is the characterization of adverse events (AE) assessed by CTCAE 4.0. The secondary objective is feasibility to manufacture a personalized neo-antigen vaccine within 6 weeks of enrolment with the PIONEER pipeline, and to evaluate the immune response before, during and after treatment with the personalized neo-antigen vaccine. And evaluate the effect on the immune response correlated to dose escalation of peptides in the vaccine. The endpoint is to evaluate the induction of adaptive immune responses to the personalized neo-antigen vaccine measured by functional assays and peptide-MHC multimer stainings. The tertiary objective is to evaluate the clinical efficacy of the treatment. The endpoints will be objective responses (OR), progression free survival (PFS) and overall survival (OS).

Detailed description

Cancer immunotherapy has shown the ability to improve the survival of patients with multiple types of advanced cancers. The human immune system can recognize the products of somatic genetic alterations in tumors, or neo-antigens, which are not expressed on normal cells. These neoantigens are an attractive immune target because their selective expression on tumors can minimize immune tolerance as well as the risk of side effects such as autoimmune reaction. Although neoantigens are ideal targets for cancer immunotherapies, most neoantigens arise from unique mutations and are not shared between individual patients. Thus, neoantigen-directed immunotherapy will need to be personalized. Novel technical advances in next-generation sequencing allow fast and systematic prediction of cancer neoantigens for each individual patient. Initial attempts of therapeutic cancer vaccination targeting individual neo-antigens have proven non-toxic and met their immunological endpoints. In this study investigators will use the proprietary platform PIONEER for fast and accurate identification of a neo-antigen vaccine tailored to each individual patient. The vaccine, based on 5-15 peptides derived from a patient's tumor individual neo-antigens, will be formulated with a novel adjuvant to strengthen CD8+ T cell immunity to cancer. Immune checkpoint inhibitors targeting PD-1 or PD-L1 will be administered both before, during and after vaccination to unleash the activity of vaccine-induced immune responses.

Conditions

• Malignant Melanoma, Metastatic
• Non Small Cell Lung Cancer Metastatic
• Bladder Urothelial Carcinoma, Metastatic

Interventions

Type	Name	Description
DRUG	EVAX-01-CAF09b	The personalised NPV-ds001 drug substance consists of multiple linear peptides (Pep-Ints) comprising natural L-amino acids dissolved in Dimethyl sulfoxide (DMSO) and 1 ml adjuvants (CAF09b) and 1,08 ml Tris buffer (25 ml).

Timeline

• Start date: 2019-01-28
• Primary completion: 2022-12-01
• Completion: 2022-12-01
• First posted: 2018-10-23
• Last updated: 2022-01-11

Locations

2 sites across 1 country: Denmark