immunotherapy

Advaxis requests orphan drug designation for treatment of HPV-associated head and neck cancer with ADXS-HPV

Source: www.marketwatch.com
Author: press release

Advaxis, Inc., a leader in developing the next generation of immunotherapies for cancer and infectious diseases, announced that it has submitted an Application for Orphan Drug Designation with the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD) for ADXS-HPV, its lead drug candidate, for the treatment of human papillomavirus (HPV)-associated head and neck cancer. There are about 50,000 new cases of head and neck cancer annually, with about 15,000 deaths. HPV infection is estimated to account for 20-50% of current incidence.

Orphan Drug Designation is granted to drug therapies intended to treat diseases or conditions that affect fewer than 200,000 people in the United States. Orphan Drug Designation entitles the sponsor to clinical protocol assistance with the FDA, as well as federal grants, tax credits, and a seven year market exclusivity period.

“HPV-associated head and neck cancer is growing at an epidemic rate in the United States and other regions throughout the world. According to the U.S. Centers for Disease Control and Prevention (CDC), over 80% of new cases occur in men, who are not typically part of HPV vaccination programs,” commented Dr. Robert Petit, Chief Scientific Officer of Advaxis. “Data from our Phase 2 study in recurrent cervical cancer show that ADXS-HPV is an active treatment in this HPV-associated cancer. We believe that ADXS-HPV immunotherapy will show similar activity in HPV-associated head and neck cancer, given the shared causality of the cancers. We have one ongoing Phase 1/2 study in HPV-positive head and neck cancer in the United Kingdom and plan to initiate another in the United States in 2013. We believe ADXS-HPV could become an important new non-cytotoxic treatment for patients with HPV-associated head and neck cancer.”

“If granted, Orphan Drug Designation (ODD) for our lead drug candidate, ADXS-HPV, could expedite our ability to help the over 10,000 Americans that the American Cancer Society estimates will be newly diagnosed with HPV-associated head and neck cancer in 2013. ODD would also provide seven years of market exclusivity for ADXS-HPV if it is approved by the FDA, tax credits on U.S. clinical trials, eligibility for orphan drug grants, and a waiver of the $1.9 million regulatory application filing fee,” commented Thomas A. Moore, Chairman and CEO of Advaxis. “It is believed that the number of new HPV-caused head and neck cancers in the United States now approaches the number of new cervical cancer cases. This indication, with these incentives, if achieved, could substantially increase the potential value of the ADXS-HPV franchise.”

About Orphan Drug Designation
Under the Orphan Drug Act (ODA), the FDA may grant orphan designation to a drug or biological product intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making a drug or biological product available in the United States for this type of disease or condition will be recovered from sales of the product. The benefits of orphan drug designation can be substantial and include federal grants, tax credits, and a seven year market exclusivity period once the product is approved, provided that the product is first to market.

In order for a sponsor to obtain orphan designation for a drug or biological product, an application must be submitted to OOPD, and the designation approved. The approval of an application for orphan designation is based upon the information submitted by the sponsor. A drug that has obtained orphan designation is said to have “orphan status.” Each designation request must stand on its own merit. Sponsors requesting designation of the same drug for the same indication as a previously designated product must submit their own data in support of their designation request. The approval of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. Safety and efficacy of a compound must be established through adequate and well-controlled studies.

Interim results from CEL-SCI’s Multikine Phase III study on head and neck cancer

Source: www.news-medical.net

CEL-SCI Corporation announced today that an interim review of the safety data from its open label, randomized, controlled, pivotal Phase III study of Multikine (Leukocyte Interleukin, Injection) investigational immunotherapy by an Independent Data Monitoring Committee (IDMC) raised no safety concerns. The IDMC also indicated that no safety signals were found that would call into question the benefit/risk of continuing the study. CEL-SCI considers the results of the IDMC review to be important since studies have shown that up to 30% of Phase III trials fail due to safety considerations and the IDMC’s safety findings from this interim review were similar to those reported by investigators during CEL-SCI’s Phase I-II trials. Ultimately, the decision as to whether a drug is safe is made by the FDA based on an assessment of all of the data from a trial.

IDMCs are committees commonly used by sponsors of clinical trials to protect the interests of the patients in ongoing trials especially when the trials involve patients with life threatening diseases, and when, as in cancer clinical trials, they extend over long periods of time (3-5 years). The committee’s membership should include physicians and clinical trial scientists knowledgeable in the appropriate disciplines, including statistics. The CEL-SCI IDMC includes prominent physicians and scientists from major institutions in the USA and abroad who are key opinion leaders in head and neck cancer and who are knowledgeable in all of the disciplines related to CEL-SCI’s study, including statistics.

The Multikine Phase III study is enrolling patients with advanced primary, not yet treated, head and neck cancer on 3 continents around the world. The objective of the study is to demonstrate a statistically significant 10% improvement in overall survival of enrolled patients who are treated with Multikine plus Standard of Care (SOC) vs. subjects who are treated with SOC only. The universally accepted current standard of care for the patient population being enrolled in the CEL-SCI study is surgery plus radiation or surgery plus concurrent radiation and chemotherapy, dependent on the risk factors for recurrence found after surgery. Multikine treated patients receive 15 local injections of Multikine over a 3 week period prior to standard of care treatment. Multikine injections are administered in the area around the tumor and in the area of the adjacent lymphnodes since those two areas are where the tumor is most likely to recur. Multikine is intended to create an anti-tumor immune response to reduce local / regional tumor recurrence and thereby increase the survival of these patients.

Multikine is the first immunotherapeutic agent being developed as a potential first-line treatment for advanced primary head and neck cancer. If it were to be approved for use following completion of our clinical development program, Multikine would become an additional and different kind of therapy in the fight against cancer: one that employs our body’s natural ability to fight tumors.

Source: CEL-SCI Corporation

October, 2012|Oral Cancer News|

Advaxis recruiting for HPV+ head and neck cancer trial

Source: www.cancertreatment.net
Author: Ross Bonander

Advaxis is announcing the enrollment of patients into the REALISTIC Phase I/II trial sponsored by Cancer Research UK to evaluate ADXS-HPV for the treatment of HPV-positive head and neck cancer. HPV has been linked to as many as seventy percent of all head and neck cancers.

ADXS-HPV is a next-generation immunotherapy that acts as a therapeutic vaccine and is being tested in trials against HPV-associated diseases, including cervical cancers.

Cancer Research UK assumes all patient costs. Advaxis seeks to recruit 45 patients.

The REALISTIC trial is being carried out at the Aintree Hospital at the University of Liverpool, the Royal Marsden Hospital at the University of London, and the Cardiff Hospital at the University of Wales. Qualified patients will have already received treatment for head and neck cancer, either surgery, radiotherapy, chemotherapy, or a combination of treatments.

Head and neck cancers account for roughly three percent of all cancers in the US, according to the American Cancer Society. They are more commonly diagnosed in men than women, and while they are traditionally linked to smoking and to alcohol consumption, HPV-related oropharyngeal cancers are on the rise among white males under 50 years of age.

“We are pleased to be working with an internationally-renowned oncology group to further expand the ADXS-HPV clinical development program to another HPV-associated tumor type,” said Advaxis Chairman & CEO Thomas A. Moore. “Through this collaboration, we hope that our proprietary technology will be able to offer a new treatment option to patients suffering from the recurrence of head and neck cancer, an important unmet medical need.”

Queensland researchers make cancer treatment breakthrough

Source: HealthCanal.com

The culmination of 10 years of collaborative research between scientists from the Queensland Institute of Medical Research (QIMR) and The University of Hong Kong (HKU) Li Ka Shing Faculty of Medicine has led to a significant breakthrough in the treatment of nasopharyngeal carcinoma (NPC), an aggressive throat cancer with a high prevalence in South-East Asia.

NPC is associated with Epstein-Barr virus infection in a manner similar to the association of hepatitis B virus and liver cancer.

By using immunotherapy, the human body’s own immune system was used to successfully fight the disease.

Professor Rajiv Khanna who heads the Australian Centre for Vaccine Development at QIMR said by enhancing the immune cells of NPC patients they have doubled the survival time of terminally ill patients.

“The presence of EBV in the cancer cells gives the body’s immune system a definite target to help battle the NPC, resulting in few side-effects,” Professor Khanna said.

“Patients who participated in the trial were in the late stages of the cancer and quite unwell, so it was important to ensure the treatment was non-invasive, non toxic and did not damage healthy cells.

“By offering such targeted treatment, we were able to increase the expected time of patient survival from 200 to over 500 days, which is an extremely positive result.

“We believe that if we offer this treatment in the earlier stages of NPC, accompanied with chemotherapy and radiation, we can further enhance survival rates.”

Twenty four NPC patients were recruited at the Queen Mary Hospital, the teaching hospital of HKU in Hong Kong and the trial has recently been expanded to the Princess Alexandra Hospital in Brisbane.

Blood was taken from patients then transported to QIMR where the white blood cells (lymphocytes) were grown and trained to specifically recognize EBV infected cancer cells. These trained immune cells (also referred to as immunotherapy) were then returned back to Hong Kong and infused into the patients where they would selectively kill EBV infected cancer cells. The patients were then closely monitored and followed up for side effects by the oncologists at the Queen Mary Hospital.

“The majority of our study participants are located in Hong Kong, but this novel immunotherapy was prepared at QIMR in Brisbane using our highly specialized manufacturing facility, Q-Gen,” Professor Khanna said.

“While there is not a high incidence of NPC in Australia, it is common amongst our population from South-East Asian background and our neighbours in China, Indonesia, Thailand, Philippines, Vietnam, Singapore and many other countries in the South-East Asian region and our work may hold the key to treating other cancers with a link to a specific virus such as glioblastoma and EBV associated lymphomas.”

Professor Khanna and his research team will be continuing their investigation of immunotherapy for the treatment of NPC at the Princess Alexandra Hospital and need NPC patients to help with their work. For more information or to volunteer, please contact: rajiv.khanna@qimr.edu.au

The results of this study have been published in Cancer Research and can be viewed at http://cancerres.aacrjournals.org/.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

February, 2012|Oral Cancer News|

CEL-SCI gets Israeli nod to commence phase III trial of multikine in head and neck cancer

Source: www.pharmabiz.com
Author: staff

CEL-SCI Corporation announced that the State of Israel’s Ministry of Health has given approval to begin enrolment of subjects for a phase III clinical trial of Multikine in Israel. Israel is one of nine countries to participate in this global phase III trial. The phase III trial will be conducted in approximately 48 clinical centres. CEL-SCI’s partner Teva Pharmaceutical Industries will be conducting the trial at three clinical centers in Israel.

The phase III trial started in the United States in late December 2010 and is expected to commence in other countries around the world within the next 30-60 days. Multikine is the company’s flagship immuno-therapy developed as a first-line standard of care in treating head and neck cancer.

CEL-SCI’s phase III clinical trial is an open-label, randomized, controlled, multi-centre study designed to determine if Multikine administered prior to current standard of care (surgery plus radiotherapy or surgery plus concurrent chemo radiotherapy) in previously untreated subjects with Advanced Primary Squamous Cell Carcinoma of the Oral Cavity/Soft Palate (Head and Neck cancer) will result in an increased overall rate of survival, versus the subjects treated with standard of care only. CEL-SCI’s 880 patient phase III trial is expected to be the largest clinical study of head and neck cancer ever conducted. It is also the first trial in which immunotherapy will be administered before any other traditional means of care are attempted. This is significant because conventional cancer therapy weakens the immune system and likely compromises the benefits of immunotherapy.

Phase II clinical trials of Multikine demonstrated that the product was safe and well-tolerated and eliminated tumours in 12% of the subjects less than a month into treatment. The Multikine treatment regimen was also shown to kill, on average, about half of the cancer cells in the subjects’ tumours before the start of standard therapy. Follow-up studies of subjects enrolled in phase II trials showed a 33% improvement in the survival rate of those treated with Multikine at a median of three and a half years following surgery. The US Food and Drug Administration granted orphan drug status to Multikine in the neoadjuvant therapy of patients with squamous cell carcinoma of the head and neck.

CEL-SCI Corporation is developing products that empower immune defenses. Its lead product, Multikine is currently being tested in a global phase III clinical trial that started in December 2010. In phase II clinical trials Multikine was shown to be safe and well-tolerated and to improve the patients overall survival by 33 percent at a median of three and half years following surgery.

April, 2011|Oral Cancer News|

Cel-Sci to bump standard of care in head, neck cancer

Source: www.bioworld.com
Author: Catherine Shaffer

Cel-Sci Corp. began a carefully designed Phase III trial of Multikine, its investigational immunotherapy for head and neck cancer. Because Multikine is designed to recruit the support of a mostly healthy immune system, Cel-Sci is making a headlong charge at the goal of first-line therapy, instead of trying to develop the product in patients who have already received surgery, radiation and chemotherapy, and have suppressed or damaged immune systems as a result. If Cel-Sci can prove the therapy works in the narrow three-week testing window granted by the FDA, Multikine stands to replace a standard of care that has changed little in half a century.

“It makes no sense to develop an immunotherapy product for late-stage patients. You should develop it as a first line therapy, ahead of radiation or chemotherapy,” Cel-Sci CEO Geert Kersten told BioWorld Today.

Vienna, Va.-based Cel-Sci’s clinical trial plan takes advantage of a nearly inevitable delay of up to six weeks between diagnosis and surgery in most head and neck cancers. The FDA has allowed Cel-Sci a three-week period to give Multikine to patients before they commence with surgery, radiation, and chemotherapy. This will not deprive any patients of the best possible standard-of-care while they also try an experimental therapy.

Head and neck cancer strikes about 500,000 people annually worldwide. Some causal factors include smoking, drinking and chewing tobacco. Most cases are diagnosed outside the U.S., and about two-thirds of patients appear with advanced disease. The standard treatment for it is surgery followed by chemotherapy with platinum-based drugs (carboplatin or cisplatin) and radiation, which is sometimes done concurrently with chemotherapy. The protocol is arduous, to say the least, and typically only extends survival by six or seven months.

Most immunotherapies are antibodies specifically targeted at a type of cancer cell. Multikine is a mixture of natural cytokines that Cel-Sci said simulates the body’s immune response. It includes interleukins, interferons, chemokines and colony-stimulating factors.

The trial will enroll 880 patients at 48 clinical centers in the U.S., Canada, Hungary, Poland, Ukraine, Russia, India, Israel and Taiwan. According to Kersten, the trial design is highly portable because the same standard of care for head and neck cancer is used around the world.

Cel-Sci partners Teva Pharmaceutical Industries Ltd., of Jerusalem, and Orient Europharma Co. Ltd., of Taiwan, will carry out studies in Israel and Taiwan, respectively, under the supervision of Cel-Sci’s global contract research organization.

Cel-Sci has not partnered Multikine in major markets like the U.S. and Europe. “We can sell ourselves there,” said Kersten. Teva and Orient will help Cel-Sci access markets in the developing world. Taiwan, especially, will be an important market, since the use of betel nut (a mild stimulant) in that country leads to a high rate of head and neck cancers.

In order to maximize Multikine’s chances of approval, Cel-Sci selected overall survival as its endpoint. Overall survival is the most bullet-proof of clinical endpoints, and, said Kersten, “Survival is the endpoint [FDA regulators] want to see these days.”

In Phase II studies, Multikine boosted overall survival by 33 percent over standard of care. Patients in the Phase II study included those with advanced primary head and neck cancer who were scheduled for their first treatment, and they were given Multikine for three weeks before the standard course. Results from the study were published in the May 2005 edition of the Journal of Clinical Oncology. The median follow-up period for the patients was 3.2 years. Survival and two-year local regional control beat the rates reported in scientific literature from 39 trials between 1987 and 2004. (See BioWorld Today, Feb. 22, 2006.)

Based on the Phase II results, Cel-Sci is optimistic about hitting statistical significance with at least a 10 percent increase in survival.

Multikine’s route of administration also differs from other immunotherapies, which are given intravenously. According to Kersten, the goal is to stimulate a localized immune response at the site of the tumor.

The therapy is injected in the vicinity of the tumor not in the tumor itself. There are two reasons for that. One is that injection directly into the tumor risks dispersing tumor cells. The second, larger reason, is that Cel-Sci is attempting to target the therapy at micrometastases that form outside of the main tumor.

It is micrometastases that cause recurrence, said Kersten, because they can’t be removed surgically. The Multikine strategy for increasing survival is to decrease the odds of metastasis by wiping out the micromets at the very earliest stage.

Kersten said that the drug has been given to 220 patients to date, with no serious adverse events. The low toxicity of Multikine will be an asset to patients who will be subjected to the highly toxic standard-of-care regime later. “Our drug wouldn’t work if it had any toxicity. You can’t add a toxic drug to anything that is horribly toxic,” he said.

December, 2010|Oral Cancer News|

HPV is changing the face of head and neck cancers

Source: www.hemonctoday.com
Author:  Christen Cona

In February, at the Multidisciplinary Head and Neck Cancer Symposium in Chandler, Ariz., Maura Gillison, MD, PhD, professor and Jeg Coughlin Chair of Cancer Research at The Ohio State University in Columbus, presented data that showed that the proportion of all head and neck squamous cell cancers that were of the oropharynx — which are most commonly HPV-positive cancers — increased from 18% in 1973 to 32% in 2005.

Maura Gillison, MD, PhD, Jeg Coughlin Chair of Cancer Research at The Ohio State University, said screening for HPV in the head and neck is years behind cervical screening for HPV. - Photo by Roman Sapecki

In addition, studies from the United States, Europe, Denmark and Australia indicate that HPV-positive patients have a more than twofold increased cancer survival than HPV-negative patients, according to Gillison.

With the rising incidence of HPV-related oropharynx cancers, it will soon be the predominant type of cancer in the oral or head and neck region, according to Andy Trotti, MD, director of radiation oncology clinical research, H. Lee Moffitt Cancer Center & Research Institute, in Tampa, Fla.

“We should be focusing on HPV-related oropharyngeal cancer because it will dominate the field of head and neck cancers for many years,” he said during an interview with HemOnc Today . “It is certainly an important population for which to continue to conduct research.”

Because HPV-associated oropharyngeal cancer is emerging as a distinct biological entity, the recent rise in incidence will significantly affect treatment, and prevention and screening techniques, essentially reshaping current clinical practice.

Social change driving incidence
In the analysis performed by Gillison and colleagues, trends demonstrated that change in the rates of head and neck cancers was largely due to birth cohort effects, meaning that one of the greatest determinants of risk was the year in which patients were born.

The increased incidence of HPV-related oropharyngeal squamous cell carcinoma started to occur in birth cohorts born after 1935, indicating that people who were aged in their teens and twenties in the 1960s were demonstrating increased incidence, Gillison said.

“Two important and probably related events happened in the 1960s. In 1964, the surgeon general published a report citing smoking as a risk factor for lung cancer, and public health policy began promoting smoking cessation along with encouragement not to start smoking,” she told HemOnc Today.

If you were 40 years old between 2000 and 2005, your risk for having HPV-related cancer is more than someone who was between the age of 40 and 45 years in 1970, according to Gillison. Social changes that occurred among people born after 1935, for example, a reduction in the number of smokers, is consistent with the increasing proportion of oropharyngeal cancers that were HPV-related.

“The rates for HPV-related cancers began to increase and the rates for HPV-unrelated cancers started to decline, consistent with the known decline in tobacco use in the U.S. population,” she said.

Now, most cases of head and neck squamous cell carcinoma in non-smokers are HPV-related; however, oral HPV infection is common and is a cause of oropharyngeal cancer in both smokers and non-smokers, research shows.

In addition to a decrease in tobacco use reducing HPV-unrelated oral cavity cancers, the number of sexual partners may have increased during this time and have helped to increase HPV-related oropharyngeal cancers, according to Gillison.

Determining the cause of the elevated incidence is only a small piece of the puzzle. Screening, establishing who is at risk, and weighing vaccination and treatment options are all relevant issues that must be addressed.

Screening is problematic
A critical area for examination and research is the issue of screening for oral cancers. In contrast to cervical cancer, there is no accepted screening that has been shown to reduce incidence or death from oropharyngeal cancer, according to Gillison.

Not many studies have examined the issue of screening for HPV-unrelated oral cancers, and the few that have, tend to include design flaws.

Gillison said there is a hope that dentists would examine the oral cavity and palpate the lymph nodes in the neck as a front-line screen for oral cancer; however, in her experience, and from her perspective as a scientist, this has never been shown to provide benefit for oral cancer as a whole.

Another caveat with regard to HPV detection is that head and neck HPV screening is about 20 years behind the cervical field.

“Clinicians screening for HPV in the field of gynecology were incredibly fortunate because Pap smear screening was already an accepted cervical cancer screening method before HPV was even identified,” she said. “There was already a treatment algorithm: If there were cytologic abnormalities, patients were referred to the gynecologist, who in turn did a colposcopy and biopsy.”

A similar infrastructure does not exist for oropharyngeal cancer. People with HPV16 oral infection are at a 15-fold higher risk for oropharynx cancer and a 50-fold increased risk for HPV-positive head and neck cancer, yet there is no algorithm for treatment and management of these at-risk individuals, Gillison said.

In 2007, WHO said there was sufficient evidence to conclude that HPV16 was the cause of oropharynx cancer, but with no clinical algorithm already established, progress in this area is much further behind.

Another problematic aspect of HPV-related oropharyngeal cancer screening is that the site where the cancer arises is not accessible to a brush sampling, according to Gillison.

“To try to find this incredibly small lesion in the submucosal area that you cannot see and cannot get access to with a brush, highlights that we need to develop new techniques, new technologies and new approaches,” she said.

The near future consists of establishing the actual rates of infection in the oral cavity and oropharynx, and then screening for early diagnosis, according to Erich Madison Sturgis, MD, MPH, associate professor in the department of head and neck surgery and the department of epidemiology at The University of Texas M.D. Anderson Cancer Center.

“I am not extremely hopeful because the oropharyngeal anatomy makes screening complicated, and these cancers likely begin in small areas within the tonsils and the base of the tongue,” Sturgis told HemOnc Today. “I am hopeful, however, that preventive vaccines will eventually, at a population level, start to prevent these cancers by helping people avoid initial infection by immunity through vaccination earlier in life.”

Much of the currently known information surrounding the issue of HPV-related oral cancers is new, so researchers continue to conduct research in various relevant areas. One key question to answer is who may be at higher risk for HPV-related oropharynx cancers.

Who is at risk?
As mentioned earlier, the number of oral sex partners seems to play a role in the risk for contracting the HPV virus.

In one study published in The New England Journal of Medicine in 2007, findings demonstrated that a high lifetime number of oral sex partners (at least six partners) was associated with an increased risk for oropharyngeal cancer (OR=3.4; 95% CI, 1.3-8.8).

In addition to a higher number of oral sex partners, other still unknown factors may be contributing to risk. This is an area that needs further research, according to Barbara Burtness, MD, chief of head and neck oncology, and professor of medical oncology at Fox Chase Cancer Center in Philadelphia.

The effect of smoking status is another area that needs further research. According to Burtness, smokers with HPV-associated oropharynx cancer have less favorable outcomes.

When discussing the prognosis of HPV-associated cancers, Sturgis said low risk is defined as low or no tobacco exposure and positive HPV status, and intermediate risk is defined as significant tobacco exposure but an HPV-positive tumor, and the highest risk group appears to be the HPV-negative group.

Although HPV-negative cancers are overwhelmingly tobacco-related cancers and tend to have multiple mutations, it appears that HPV-positive cancers, particularly those in patients with low tobacco and alcohol exposure, tend to lack mutations and to have a better prognosis, and this may ultimately help to guide treatment practices, according to Sturgis. Yet, there is still much to learn about HPV-related oropharyngeal cancers on various fronts.

Vaccination a hopeful ally
In HPV-related head and neck cancer, particularly oropharynx cancers, more than 90% of patients who have an HPV-type DNA identified, have type 16, according to Sturgis.

The two current HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), which are approved for cervical cancers, include HPV types 16 and 18; therefore, in theory, they should be protective against the development of infections in the oropharynx and protective at preventing these HPV-associated cancers from occurring.

The presumption is that if there was a population-wide vaccination against HPV, there would be less person-to-person transmission, and this would lead to fewer oropharynx cancers, according to Burtness, who said this theory still needs further research.

There is excitement at the possibility that therapeutic vaccines could be developed, and various groups are investigating this, Burtness added.

“There is reason to think that the vaccines may be helpful; however, when HPV infects the tonsillar tissues, it exerts control in the host cells by making two proteins: E6 and E7; so another potentially exciting therapeutic avenue would be to target those specific viral proteins,” she told HemOnc Today.

Anxiety about protection from the HPV virus is palpable, according to Sturgis. He described the worry that many patients experience about contracting and transmitting HPV infection.

“Many patients are concerned they will put their spouses and/or children at risk in ways such as kissing them; and we need to tone down those worries until we have better data,” he said.

Screening and vaccination are fundamental aspects of current ongoing research, but of equal importance is determining what clinicians should do to treat a population of patients with HPV-related oropharyngeal cancers.

HPV status may influence treatment
With rates of HPV-related cancers escalating, determining the appropriate treatment for these patients is crucial.

During the past 10 years, findings from retrospective studies have shown that patients with HPV-related cancers have a much better prognosis than patients who test negative for HPV. Findings from several retrospective analyses from clinical trials conducted during the past 2 years have come to the same conclusion, according to Gillison: HPV-positive patients have half the risk for death compared with patients negative for HPV.

Therefore, there may be several alternative treatment options, including the possibility of reducing the dose of radiation given to patients after chemotherapy, thereby reducing toxicity.

Comparing HPV-negative and HPV-positive patients may not be enough to determine proper treatment, researchers said. Data between different cohorts of HPV-positive patients also needs to be examined. Smoking, for example, may play a role in patient outcome.

In a prospective Radiation Therapy Oncology Group clinical trial (RTOG 0129), presented by Gillison at the 2009 ASCO Annual Meeting and recently published in The New England Journal of Medicine (see page 53), researchers conducted a subanalysis of the effect of smoking on outcome in uniformly staged and treated HPV-positive and HPV-negative patients while accounting for a number of potential confounders. HPV-positive patients who were never smokers had a 3-year OS of 93% compared with heavy smoking HPV-negative patients who had an OS of 46%.

The study found that smoking was independently associated with OS and PFS. Patients had a 1% increased risk for death and cancer relapse for each additional pack-year of smoking. This risk was evident in both HPV-positive and HPV-negative patients. Gillison said smoking data must be paid attention to, and she encouraged cooperative group research on the topic.

Most of the findings demonstrate improved outcomes for patients with HPV-positive oropharyngeal cancers vs. patients with HPV-negative oropharyngeal cancers, according to the experts interviewed by HemOnc Today.

Dose de-intensification for less toxicity
To date, there is no evidence that HPV-related cancers should be managed differently than HPV-unrelated cancers, but it is a hot topic among clinicians in the field, according to Burtness.

The superior outcomes for HPV-associated oropharynx cancer have suggested the possibility of treatment de-intensification. The use of effective induction chemotherapy may permit definitive treatment with a lower total radiation dose. In theory, this would reduce the severity of late toxic effects of radiation, such as swallowing dysfunction. Such a trial is being conducted by the Eastern Cooperative Oncology Group. Burtness said this is currently pure research question.

“There is still much research that needs to be done before clinicians can safely reduce the dose of radiation administered to HPV-positive patients,” Burtness said.

Currently, she and colleagues in the ECOG are conducting a study of patients with HPV-associated stage III or IV oropharynx cancers to examine the possibility of tailoring therapy to these patients. Patients are assigned to one of two groups: low-dose intensity-modulated radiotherapy 5 days per week for 5 weeks (27 fractions) plus IV cetuximab (Erbitux, ImClone) once weekly for 6 weeks, or standard-dose intensity-modulated radiotherapy 5 days per week for 6 weeks (33 fractions) plus IV cetuximab once weekly for 7 weeks.

If patients have a very good clinical response to chemotherapy, which is likely to happen with HPV-associated cancers, they are eligible to receive a reduced dose of radiation, and hopefully, they would experience less adverse effects, Burtness said.

“Patients who are treated with the full course of radiation for head and neck cancer are now getting 70 Gy, and they are often left with dry mouth, and speech and swallowing difficulty,” she said. “We are hopeful that if these particular cancers are treatment responsive to chemotherapy, we may be able to spare the patient the last 14 Gy of radiation.”

Immunotherapy a viable treatment
Another possible treatment technique that may benefit patients with HPV-related cancers is immunotherapy. One form of immunotherapy uses lymphocytes collected from the patient, and training the cells in the laboratory to recognize in this case a virus that is associated with a tumor and consequently attack it. This approach potentially may be used to treat HPV-related oropharynx cancers, according to Carlos A. Ramos, MD, assistant professor at the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston.

“With some infections that lead to cancer, even though the virus is present in the tumor cells, the proteins shown to the immune system are limited; therefore, they do not drive a very strong immune response,” Ramos told HemOnc Today. “Training the immune system cells, T lymphocytes, may make them respond better to antigens.”

Data from ongoing trials that are taking T lymphocytes from patients and educating them to recognize antigens in patients with the Epstein-Barr virus associated tumors have shown some activity against them, according to Ramos. This adoptive transfer appears to be safe and may have the same effect on the HPV virus associated tumors. Immunotherapy does not cause the usual toxicities associated with chemotherapy, he said.

“There are currently no trials showing whether we can prevent more recurrences with this approach, but the results of trials examining viruses such as Epstein-Barr are good so far, in both patients who have no evidence of disease and in those who still have disease,” he said.

Even patients with active disease who have not responded to other therapies have responded to this therapy, Ramos said. He and colleagues are working toward compiling preclinical data to study the possibility of using immunotherapy to treat patients with HPV-related cancers.

Journey is just beginning
Much of what is known about risk, screening, prevention and treatment of HPV-related oropharynx cancers is in the early stages of discovery and much is still theoretical, according to Sturgis.

“As far as we can tell, these infections are transmitted sexually; the hope is that as we have better vaccines for prevention of cervical dysplasia, the downstream effect will help prevent other HPV-related cancers, such as anal cancers and penile cancers and oropharyngeal cancers,” he said.

Several recent studies examining new therapies that may reduce the intensity of traditional treatments while maintaining survival rates would have a major effect on the field, according to Sturgis.

Gillison said the rise in the number of cases of HPV-related cancers is changing the patient population considered to be at risk, and more research is vital.

“The most important thing for clinicians to do is be aware that trials are being developed and strongly encourage their patients to participate,” she said.

Completion of Cel-Sci’s new facility signals that long awaited phase III trial is imminent

Source: www.reuters.com
Author: press release

BioMedReports, the news portal which covers Wall Street’s biomedical sector and delivers financial and investment intelligence to a community of highly informed investors, was given an exclusive tour of CEL-SCI Corporation’s new, state-of-the-art manufacturing facility near Baltimore, MD where the potentially ground breaking cancer immunotherapy treatment, Multikine, will be manufactured to support an upcoming Phase III clinical trial.

Multikine is the company’s flagship immunotherapeutic head and neck cancer treatment and is the first immunotherapeutic agent being developed as a first-line standard of care cancer treatment. Because it required a very specific cold-fill process for manufacturing, the Phase III trials have been on hold as Cel Sci dedicated the majority of their time and resources to build the new best-in-class production facility.

Additionally, once the facility is validated, Cel Sci will become the only entity offering the 4°C cold fill on a contract basis, meaning the potential to bring in significant revenue as an added bonus does exist.

October, 2009|Oral Cancer News|

GSK partners with Enigma, Abbott on cancer immunotherapy project

Source: bioopticsworld.co
Author: staff

Pharmaceuticals company, Abbott (Des Plaines, IL), announced an agreement with GSK to develop an automated molecular diagnostic test, also based on RT-PCR technology, to screen non-small cell lung cancer (NSCLC) tumors for expression of the MAGE-A3 antigen. GSK’s MAGE-A3 ASCI (antigen specific cancer immunotherapy) candidate is currently being evaluated as an adjuvant treatment in resected NSCLC in the Phase III clinical study MAGRIT, the largest lung cancer treatment study ever conducted.

Fast, accurate influenza testing
The GSK-Enigma partnership aims for joint development of the Enigma ML (mini laboratory) PCR platform to deliver fully-automated results from swab samples in less than 60 minutes at the point of care–to the same accuracy standards as reference laboratories. Thus, patients can be tested for specific influenza subtypes and quickly receive appropriate treatment. Operators of the Enigma ML system will not require specialist training.

A trial involving working prototypes of the ML system with front line health care providers across Europe is planned for Q4 2009. Launch of Enigma ML is anticipated in early 2011, subject to successful clinical trials and regulatory approval.

Cancer immunotherapy
Under terms of the GSK-Abbott agreement, the partners will develop and commercialize an RT-PCR test–designed to detect MAGE A3–for use on the Abbott m2000 automated instrument system.

“This is an exciting collaboration with a leading company in cancer immunotherapy research,” said Stafford O’Kelly, head of Abbott’s molecular diagnostics business. “The agreement is indicative of our focus on personalized medicine and developing analytical molecular tools to identify patients most likely to benefit from important pharmacogenomic therapies.”

Currently, there are no nucleic acid based tests approved by the U.S. Food and Drug Administration for use in identifying patients who may derive treatment benefits from targeted non-small cell lung cancer therapies.

“Lung cancer is the biggest cancer killer globally,” said Vincent Brichard, M.D., Ph.D., vice president and head of Immunotherapeutics, GSK. “Through this partnership we aim to make MAGE-A3 testing of lung tumors available in standard pathology labs around the world. This means patients globally could be able to find out if they are eligible and can potentially benefit from targeted cancer treatment against this antigen, such as GSK’s MAGE-A3 candidate ASCI.” MAGE-A3 is a tumor-specific antigen that is expressed in non-small cell lung cancer and a wide variety of other cancers (including melanoma, head and neck cancer, and bladder cancer), but not in normal cells. To be eligible to receive GSK’s MAGE A3 ASCI, patients must have MAGE-A3 expressing NSCLC tumors.

GSK says its ASCIs represent a novel class of medicines designed to train the immune system to recognize and eliminate cancer cells in a highly specific manner. They combine tumor antigens, delivered as purified recombinant proteins, and GSK’s proprietary Adjuvant Systems, which are specific combinations of immunostimulating compounds selected to increase the anti-tumor immune response. ASCIs are being investigated in the clinic to support their use to reduce the risk of tumor recurrence following surgery, or to impact tumor growth in an early metastatic setting. The highly specific mode of action of GSK’s ASCIs allows development of diagnostic tools to aid in selecting patients eligible for the treatment, depending on the expression of the tumor antigens.

MAGE-A3 protein has been in-licensed by GSK from the Ludwig Institute for Cancer Research, the largest international academic institute dedicated to understanding and controlling cancer. MAGE-A3 ASCI is an investigational compound and it is not approved for use in any indication in any country at this time.