Madison Vaccines Announces Patient Dosing Underway in Clinical Trial Pairing Its Lead Prostate Cancer Vaccine, MVI-816, with PD1 Inhibitor Pembrolizumab

“Madison Vaccines Incorporated (MVI) today announced dosing has begun in a combination trial for MVI-816 (pTVG-HP), its lead prostate cancer vaccine, paired with pembrolizumab (Keytruda®), a PD-1 inhibitor, also called a checkpoint inhibitor. A PD-1 inhibitor works by exposing cancer cells to attack by the immune system by preventing the cancer cells from blocking an effective immune response. MVI-816, already in a Phase 2 clinical trial as monotherapy, has been shown to induce persistent T-cell responses in prostate cancer patients. The combination trial will test the hypothesis that both treatments work together synergistically. The first-of-its kind combination to reach this stage will be tested in men with metastatic, castrate-resistant prostate cancer, and will be conducted at the University of Wisconsin – Madison, Carbone Cancer Center under the direction of Douglas McNeel, MD, PhD, a leading prostate cancer researcher at the university.”


Generex Provides Data Update from AE37 Phase II Breast Cancer Trial One Year Post Completion of Enrollment

“Generex Biotechnology Corporation (www.generex.com) (OTCQB: GNBT) announced today that updated data from the on-going Phase II clinical trial of the AE37 breast cancer vaccine under development at the Company’s wholly-owned subsidiary, Antigen Express, Inc. (www.antigenexpress.com), will be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).  The current analysis was performed on data that was examined one year after the last patient was enrolled into the trial.  The ASCO meeting will be held from May 29 to June 2, 2015 in Chicago, IL.

“The abstract, entitled ‘Final Pre-specified Analysis of the Phase II Trial of the AE37+GM-CSF Vaccine in High Risk Breast Cancer Patients to Prevent Recurrence”, by Julia Greene, et al will be presented on May 30 during the Breast Cancer – HER2/ER session.  The study reports on the anticipated five year disease free survival in patients enrolled in a controlled, randomized, and single-blinded Phase II trial that completed enrollment in January of 2014.  A prior interim analysis conducted in 2011, as well as a primary efficacy analysis conducted in 2013, pointed to a benefit of the AE37 vaccine in patients not receiving Herceptin and, in particular, patients with triple negative breast cancer.  This latter group represents a patient population of high unmet need.  The present study continues to show a trend in this population, with a 35% reduction in the relative risk of recurrence in patients receiving the AE37 vaccine.”


Cuba Has a Lung Cancer Vaccine—And America Wants It

“Cuba has for several years had a promising therapeutic vaccine against lung cancer. The 55-year trade embargo led by the US made sure that Cuba was mostly where it stayed. Until—maybe—now.

“The Obama administration has, of course, been trying to normalize relations with the island nation. And last month, during New York Gov. Andrew Cuomo’s visit to Havana, Roswell Park Cancer Institute finalized an agreement with Cuba’s Center for Molecular Immunology to develop a lung cancer vaccine and begin clinical trials in the US. Essentially, US researchers will bring the Cimavax vaccine stateside and get on track for approval by the Food and Drug Administration.

“ ‘The chance to evaluate a vaccine like this is a very exciting prospect,’ says Candace Johnson, CEO of Roswell Park. She’s excited, most likely, because research on the vaccine so far shows that it has low toxicity, and it’s relatively cheap to produce and store. The Center for Molecular Immunology will give Roswell Park all of the documentation (how it’s produced, toxicity data, results from past trials) for an FDA drug application; Johnson says she hopes to get approval for testing Cimavax within six to eight months, and to start clinical trials in a year.”


Breakthrough Development in Cancer Immunology Published in Nature

“BioNTech AG announced the publication of a scientific article on therapeutic immune responses to cancer in the internationally renowned scientific journal Nature. The paper shows an important scientific foundation for the clinical development of truly personalized yet broadly applicable cancer treatment for any patient. This publication represents results from an interdisciplinary collaboration between scientific and clinical teams at TRON, La Jolla Institute for Allergy and Immunology and BioNTech AG to elucidate novel cancer immunotherapy principles, translate these into individually tailored mRNA cancer vaccines and progress clinical development to provide new treatment options for cancer patients.

“The article, titled ‘Mutant MHC II epitopes drive therapeutic immune responses to cancer,’ describes a novel immunological principle relevant to cancer immunotherapy and how this translates into patient specific mRNA cancer vaccines targeting multiple mutations. Ugur Sahin, co-founder and CEO of BioNTech and colleagues, identified tumor-specific mutations capable of inducing immune responses in mouse models of skin, breast and colon cancer, and showed that a large fraction of these mutations can be recognized by immune cells called CD4+T cells. The study shows that the proportion of mutations recognized by immune cells is at least ten times higher than previously reported. The finding is extremely important as immune recognition of tumor-specific mutations has been previously shown to be required for clinically successful cancer immunotherapy.”


Phase 3 Trial to Compare PV-10 with Chemotherapy in Stage III Melanoma

“Recruitment will begin soon for a phase 3 trial that will compare intralesional PV-10 with chemotherapy in patients with stage IIIb or IIIc melanoma, according to a presenter at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

“The analysis will include 225 patients. Two-thirds will be randomly assigned to monthly injections with PV-10 (Provectus), a sterile, non-pyrogenic solution of rose bengal disodium that destroys tumors by necrosis. The other patients will be assigned standard-dose chemotherapy with dacarbazine or temozolomide.

“All patients must have cutaneous and subcutaneous disease with no active nodal disease, and all lesions must be BRAF wild type. All patients must be either refractory to or not candidates for systemic immunotherapy.

“ ‘This is a trial design that is difficult to do,’ Sanjiv S. Agarwala, MD, chief of oncology and hematology at St. Luke’s Cancer Center, professor at Temple University School of Medicine and a HemOnc Today Editorial Board member, said during a presentation. ‘We’re going to need a lot of centers, and there will be smaller groups per center because these are not easy patients to find. But we’re not going to deprive patients of the ability to get checkpoint inhibitors if that is the right treatment for them.’ ”


Celldex Therapeutics Announces Initiation of Phase 1/2 Study of Varlilumab in Combination with Ipilimumab and CDX-1401 in Metastatic Melanoma

“Celldex Therapeutics, Inc. (CLDX) today announced the initiation of a Phase 1/2 safety pilot and expansion study examining the investigational combination of varlilumab and ipilimumab (Yervoy(R); Bristol-Myers Squibb) in patients with Stage III or IV metastatic melanoma. Varlilumab is Celldex’s fully human monoclonal antibody that targets CD27, a critical co-stimulatory molecule in the immune activation cascade. Ipilimumab, a recombinant, human monoclonal antibody that blocks CTLA-4, is FDA approved for the treatment of unresectable or metastatic melanoma. In the Phase 2 portion of the study, patients with tumors that express NY-ESO-1 will also receive CDX-1401, Celldex’s off-the-shelf antibody-based dendritic cell vaccine that targets tumors expressing the NY-ESO-1 oncoprotein.

“The three agents in this study were specifically selected because they uniquely intervene at key points of immune regulation and because Celldex has observed enhanced activity in preclinical studies when varlilumab is combined with either checkpoint inhibitors or with vaccines. In addition, this study will also build on previous clinical data from the CDX-1401 experience that suggests that CDX-1401 may predispose patients to better outcome on checkpoint inhibitors, including ipilimumab. “We believe sophisticated combination approaches centered on immunotherapy hold significant promise for the treatment of cancer and, to this end, are committed to exploring novel combinations across a broad array of mechanisms and indications. This latest trial marks the third Phase 1/2 combination study that varlilumab has entered and the first three-drug combination study,” said Thomas Davis, MD, Executive Vice President and Chief Medical Officer of Celldex Therapeutics.”


Personalized Vaccines May Hold Promise for Melanoma Treatment

“Personalized melanoma vaccines can be used to marshal a powerful immune response against unique mutations in patients’ tumors, according to early data in a first-in-people clinical trial at Washington University School of Medicine in St. Louis.

“The tailor-made vaccines, given to three with advanced melanoma, appeared to increase the number and diversity of -fighting T responding to the tumors. The finding is a boost to cancer immunotherapy, a treatment strategy that unleashes the immune system to seek out and destroy cancer.

“The research is reported April 2 in Science Express, in a special issue devoted to cancer immunology and immunotherapy.”


Bavarian Nordic Vaccine Helps Prolong Life in Prostate Cancer Trial

“An experimental therapeutic vaccine from Danish drugmaker Bavarian Nordic helped significantly extend survival in patients with advanced prostate cancer, according to results of a small early-stage trial conducted by the U.S. National Cancer Institute.

“Shares of Bavarian Nordic closed up almost 12 percent in Copenhagen after the company released the data on Tuesday.

“The study involved 30 patients with prostate cancer that had failed to benefit from standard treatments that reduce levels of testosterone, the male hormone that fuels the cancer.

“Patients were treated with the company’s Prostvac vaccine, in addition to escalating doses of Bristol-Myers Squibb Co’s Yervoy, an approved injectable treatment for advanced melanoma that works by taking the brakes off the body’s immune system.”


3-D Vaccine Spontaneously Assembles to Pack a Powerful Punch against Cancer, Infectious Diseases

Editor’s note: The immune system-boosting treatment discussed in this article has not yet been tested in patients. Nonetheless, this article provides a good explanation of cancer vaccines.

“NIBIB-funded researchers have developed a novel 3D vaccine that could provide a more effective way to harness the immune system to fight cancer as well as infectious diseases. The vaccine spontaneously assembles into a scaffold once injected under the skin and is capable of recruiting, housing, and manipulating immune cells to generate a powerful immune response. The vaccine was recently found to be effective in delaying tumor growth in mice.

” ‘This vaccine is a wonderful example of applying biomaterials to new questions and issues in medicine,’ says David Mooney, Ph.D., a professor of bioengineering at Harvard University in the School of Engineering and Applied Sciences, whose lab developed the vaccine. The project was co-led by Jaeyun Kim, Ph.D. and Aileen Li, a doctoral student in the Mooney lab. Their findings were published in the December 8, 2014 issue of Nature Biotechnology.

“Cancer cells are generally ignored by the immune system. This is because — for the most part — they more closely resemble cells that belong in the body than pathogens, such as bacterial cells or viruses. The goal of cancer vaccines is to provoke the immune system to recognize cancer cells as foreign and attack them.

“One way to do this is by manipulating dendritic cells, the coordinators of immune system behavior. Dendritic cells constantly patrol the body, sampling bits of protein found on the surface of cells or viruses called antigens. When a dendritic cell comes in contact with an antigen that it deems foreign, it carries it to the lymph nodes, where it instructs the rest of the immune system to attack anything in the body displaying that antigen.”