Personalized Neo-antigen Vaccine in Advanced Solid Tumors (NeoPepVac) (NeoPepVac)
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|ClinicalTrials.gov Identifier: NCT03715985|
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : April 8, 2019
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. 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).
|Condition or disease||Intervention/treatment||Phase|
|Malignant Melanoma, Metastatic Non Small Cell Lung Cancer Metastatic Kidney Cancer Metastatic||Drug: EVAX-01-CAF09b||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Not a randomized study. 25 patients to be included. Group A) has not yet started standard treatment Group B) has begun standard treatment at least 4 months before first vaccine, and the decease development is status quo.|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Actual Study Start Date :||January 28, 2019|
|Estimated Primary Completion Date :||January 1, 2021|
|Estimated Study Completion Date :||January 1, 2022|
Group A (has not yet started standard treatment) and Group B (has begun standard treatment at least 4 months before first vaccine, and the decease development is status quo) will receive 6 vaccines in total. Firstly 3 vaccines intraperitoneal biweekly and lastly 3 vaccines intramuscular biweekly while the patients are receiving standard immune therapy.
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).
Other Name: NPV-ds001-CAF09b
- Number and type of reported adverse events [ Time Frame: 0-100 weeks ]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.
- Treatment related immune responses [ Time Frame: 0-100 weeks ]To evaluate the immunological impact of the treatment. Elispot and tetramer staining methods will be applied to identify NeoPepVac specific T cells in the blood over time
- Overall survival [ Time Frame: 3 years ]Overall survival (OS), defined as the time from the start of treatment to death, will be described with the Kaplan-Meier curve.
- Objective response rate Progression free survival [ Time Frame: 3 years ]Progression-free survival (PFS), defined as the time from start of treatment to disease progression, relapse or death due to any cause, whichever is earlier, will be described with the Kaplan-Meier curve.
- Objective response rate [ Time Frame: 3 years ]Tumor responses will be evaluated using RECIST1.1 for the assessment of efficacy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03715985
|Contact: Sofie K Moerk, MDfirstname.lastname@example.org|
|Contact: Inge Marie Svane, Prof., MDemail@example.com|
|Herlev Hospital, Center for Cancer Immune Therapy,||Recruiting|
|Herlev, Denmark, 2730|
|Contact: Sofie K Moerk, MD|
|Herlev, Denmark, 2730|
|Contact: Sofie K Moerk, MD|
|Principal Investigator:||Inge Marie Svane, Prof., MD||CCIT (Center for Cancer Immune Therapy)|