A Phase 1 Dose-Escalation Study of ADXS-NEO Expressing Personalized Tumor Antigens, Alone and in Combination With Pembrolizumab in Subjects With Advanced or Metastatic Solid Tumors

This is a Phase 1, open-label, multicenter study of ADXS-NEO administered alone and in combination with pembrolizumab in participants with select advanced or metastatic solid tumors. This study will be performed in 2 phases, a safety phase (Part A and Part B) and an efficacy phase (Part C).

Start Date28 Mar 2018

Sponsor / Collaborator

Advaxis, Inc.

100 Clinical Results associated with Neoepitope-based immunotherapies(Advaxis, Inc.)

100 Translational Medicine associated with Neoepitope-based immunotherapies(Advaxis, Inc.)

100 Patents (Medical) associated with Neoepitope-based immunotherapies(Advaxis, Inc.)

Literatures (Medical) associated with Neoepitope-based immunotherapies(Advaxis, Inc.)

01 Apr 2021·Cancer Immunology, ImmunotherapyQ2 · MEDICINE

Combination therapies utilizing neoepitope-targeted vaccines

Q2 · MEDICINE

Review

Author: Schlom, Jeffrey ; Hamilton, Duane H ; Lee, Karin L

AbstractClinical successes have been achieved with checkpoint blockade therapy, which facilitates the function of T cells recognizing tumor-specific mutations known as neoepitopes. It is a reasonable hypothesis that therapeutic cancer vaccines targeting neoepitopes uniquely expressed by a patient’s tumor would prove to be an effective therapeutic strategy. With the advent of high-throughput next generation sequencing, it is now possible to rapidly identify these tumor-specific mutations and produce therapeutic vaccines targeting these patient-specific neoepitopes. However, initial reports suggest that when used as a monotherapy, neoepitope-targeted vaccines are not always sufficient to induce clinical responses in some patients. Therefore, research has now turned to investigating neoepitope vaccines in combination with other cancer therapies, both immune and non-immune, to improve their clinical efficacies.

01 Jan 2021·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

Use of plasma ctDNA as a potential biomarker for longitudinal monitoring of a patient with metastatic high-risk upper tract urothelial carcinoma receiving pembrolizumab and personalized neoepitope-derived multipeptide vaccinations: a case report

Q2 · MEDICINE

Author: Kelkenberg, Sabine ; Frick, Maximilian ; Pieper, Natalia ; Kayser, Simone ; Hadaschick, Dirk ; Blumendeller, Carolin ; Kopp, Maria ; Battke, Florian ; Schulze, Martin ; Boehme, Julius ; Biskup, Saskia ; Stenzl, Arnulf ; Bartsch, Oliver ; Rinckleb, Antje ; Kyzirakos, Christina

Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Only limited data are available concerning therapeutic regimes and potential biomarkers for disease monitoring. Standard therapies often provide only insufficient treatment options. Hence, immunotherapies and complementary approaches, such as personalized neoepitope-derived multipeptide vaccine (PNMV), come into focus. In this context, genetic analysis of tumor tissue by whole exome sequencing represents an essential diagnostic step in order to calculate tumor mutational burden (TMB) and to reveal tumor-specific neoantigens. Furthermore, disease progression is essential to be monitored. Longitudinal screening of individually known mutations in plasma circulating tumor DNA (ctDNA) by the use of next-generation sequencing and digital droplet PCR (ddPCR) might be a promising method to fill this gap.Here, we present the case of a 55-year-old man who was diagnosed with high-risk metastatic UTUC in 2015. After initial surgery and palliative chemotherapy, he developed recurrence of the tumor. Genetic analysis revealed a high TMB of 41.2 mutations per megabase suggesting a potential success of immunotherapy. Therefore, in 2016, off-label treatment with the checkpoint-inhibitor pembrolizumab was started leading to strong regression of the disease. This therapy was then discontinued due to side effects and treatment with a previously produced PNMV was started that induced strong T cell responses. During both treatments, plasma Liquid Biopsies (pLBs) were performed to measure the number of mutated molecules per mL plasma (MM/mL) of a known tumor-specific variant in the MLH1 gene by ddPCR for longitudinal monitoring. Under treatment, MM/mL was constantly zero. A few months after all therapies had been discontinued, an increase of MM/mL was detected that persisted in the following pLBs. When MRI scans proved tumor recurrence, treatment with pembrolizumab was started again leading to a rapid decrease of MM/mL in the pLB to again zero. Treatment response was then also confirmed by MRI.This case shows that use of immunotherapy and PNMV might be a promising treatment option for patients with high-risk metastatic UTUC. Furthermore, measurement of individually known tumor mutations in plasma ctDNA by the use of pLB could be a very sensitive biomarker to longitudinally monitor disease.

01 Aug 2019·Cancer Immunology ResearchQ1 · MEDICINE

Efficient Tumor Clearance and Diversified Immunity through Neoepitope Vaccines and Combinatorial Immunotherapy

Q1 · MEDICINE

Article

Author: Lee, John H. ; Sanborn, John Z. ; Rabizadeh, Shahrooz ; Palena, Claudia ; Lee, Karin L. ; Su, Zhen ; Rohlin, Lars ; Soon-Shiong, Patrick ; Nguyen, Andrew ; Niazi, Kayvan ; Schlom, Jeffrey ; Gameiro, Sofia R. ; Benz, Stephen C. ; Hicks, Kristin C. ; Hamilton, Duane H. ; Ordentlich, Peter

AbstractProgressive tumor growth is associated with deficits in the immunity generated against tumor antigens. Vaccines targeting tumor neoepitopes have the potential to address qualitative defects; however, additional mechanisms of immune failure may underlie tumor progression. In such cases, patients would benefit from additional immune-oncology agents targeting potential mechanisms of immune failure. This study explores the identification of neoepitopes in the MC38 colon carcinoma model by comparison of tumor to normal DNA and tumor RNA sequencing technology, as well as neoepitope delivery by both peptide- and adenovirus-based vaccination strategies. To improve antitumor efficacies, we combined the vaccine with a group of rationally selected immune-oncology agents. We utilized an IL15 superagonist to enhance the development of antigen-specific immunity initiated by the neoepitope vaccine, PD-L1 blockade to reduce tumor immunosuppression, and a tumor-targeted IL12 molecule to facilitate T-cell function within the tumor microenvironment. Analysis of tumor-infiltrating leukocytes demonstrated this multifaceted treatment regimen was required to promote the influx of CD8+ T cells and enhance the expression of transcripts relating to T-cell activation/effector function. Tumor-targeted IL12 resulted in a marked increase in clonality of T-cell repertoire infiltrating the tumor, which when sculpted with the addition of either a peptide or adenoviral neoepitope vaccine promoted efficient tumor clearance. In addition, the neoepitope vaccine induced the spread of immunity to neoepitopes expressed by the tumor but not contained within the vaccine. These results demonstrate the importance of combining neoepitope-targeting vaccines with a multifaceted treatment regimen to generate effective antitumor immunity.

100 Deals associated with Neoepitope-based immunotherapies(Advaxis, Inc.)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Head and neck cancer metastatic	Phase 2	US	Advaxis, Inc.	28 Mar 2018
Metastatic colon cancer	Phase 2	US	Advaxis, Inc.	28 Mar 2018
Metastatic melanoma	Phase 2	US	Advaxis, Inc.	28 Mar 2018
metastatic non-small cell lung cancer	Phase 2	US	Advaxis, Inc.	28 Mar 2018
Metastatic Solid Tumor	Phase 2	US	Advaxis, Inc.	28 Mar 2018
Transitional Cell Carcinoma	Phase 2	US	Advaxis, Inc.	28 Mar 2018
Bladder Cancer	Phase 1	-	Amgen, Inc.	-
Colorectal Cancer	Phase 1	-	Amgen, Inc.	-

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