FDA

FDA Approves First Gene Therapy For Leukemia

Source: npr.org
Author: Rob Stein
Date: August 30, 2017

The Food and Drug Administration on Wednesday announced what the agency calls a “historic action” — the first approval of a cell-based gene therapy in the United States.

The FDA approved Kymriah, which scientists refer to as a “living drug” because it involves using genetically modified immune cells from patients to attack their cancer.

The drug was approved to treat children and young adults up to age 25 suffering from a form of acute lymphoblastic leukemia who do not respond to standard treatment or have suffered relapses.

The disease is a cancer of blood and bone marrow that is the most common childhood cancer in the United States. About 3,100 patients who are 20 and younger are diagnosed with ALL each year.

“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” FDA Commissioner Scott Gottlieb said in a written statement.

“New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses,” Gottlieb said.

The treatment involves removing immune system cells known as T cells from each patient and genetically modifying the cells in the laboratory to attack and kill leukemia cells. The genetically modified cells are then infused back into patients. It’s also known as CAR-T cell therapy.

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.

“Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials,” Marks said in the FDA statement.

The treatment, which is also called CTL019, produced remission within three months in 83 percent of 63 pediatric and young adult patients. The patients had failed to respond to standard treatments or had suffered relapses. Based on those results, an FDA advisory panel recommended the approval in July.

The treatment does carry risks, however, including a dangerous overreaction by the immune system known as cytokine-release syndrome. As a result, the FDA is requiring strong warnings.

In addition, the treatment will be initially available only at 32 hospitals and clinics that have been specially trained in administering the therapy.

Novartis, which developed the drug, says the one-time treatment will cost $475,000 for patients who respond. People who do not respond within a month would not be charged, and the company said it is taking additional steps to make sure everyone who needs the drug can afford it

But some patient advocates criticized the cost nevertheless.

“While Novartis’ decision to set a price at $475,000 per treatment may be seen by some as restraint, we believe it is excessive,” says David Mitchell, founder and president of Patients For Affordable Drugs. “Let’s remember, American taxpayers invested over $200 million in CAR-T’s discovery.”

August, 2017|Oral Cancer News|

U.S. FDA removes clinical hold on CEL-SCI’s phase 3 head & neck cancer trial

Source: www.businesswire.com
Author: press release

CEL-SCI Corporation today announced it has received a letter from the U.S. Food and Drug Administration (FDA) stating that the clinical hold that had been imposed on the Company’s Phase 3 cancer study with Multikine* (Leukocyte Interleukin, Inj.) has been removed and that all clinical trial activities under this Investigational New Drug application (IND) may resume.

Multikine is being studied as a potential first-line (before any other cancer treatment is given) immunotherapy that is aimed at harnessing the patient’s own immune system to produce an anti-tumor response. Nine hundred twenty-eight (928) newly diagnosed head and neck cancer patients have been enrolled in this Phase 3 cancer study and all the patients who have completed treatment continue to be followed for protocol-specific outcomes in accordance with the Study Protocol.

The study’s primary endpoint is a 10% increase in overall survival for patients treated with the Multikine treatment regimen plus standard of care (SOC) versus those who receive SOC only. The determination if the study’s primary end point has been met will occur when there are a total of 298 deaths in those two groups. Current SOC for this indication is surgery, followed by radiation therapy alone or followed by concurrent radio-chemotherapy.

There is a clear and unmet medical need for a new treatment in this indication as the last FDA approved treatment for advanced primary head and neck cancer was over 50 years ago. The FDA has also designated Multikine an Orphan Drug for neoadjuvant therapy in patients with squamous cell carcinoma of the head and neck (SCCHN).

About Head and Neck Cancer
Head and neck cancer describes squamous cell carcinomas located inside the neck, mouth, nose, and throat. According to the World Health Organization, the annual incidence of head and neck cancer is approximately 550,000 cases worldwide, with about 300,000 deaths each year. Risk factors involved with head and neck cancer include heavy alcohol use, tobacco use, and the cancer causing type of human papilloma virus (HPV).

About CEL-SCI Corporation
CEL-SCI’s work is focused on finding the best way to activate the immune system to fight cancer and infectious diseases. The Company has operations in Vienna, Virginia, and in/near Baltimore, Maryland.

August, 2017|Oral Cancer News|

FDA Warns Against So-Called “Cancer Cure”

Source: http://www.curetoday.com/articles/fda-warns-against-socalled-cancer-cure

Published: 01/13/2017

Author: BRIELLE URCIUOLI

The US Food and Drug Administration (FDA) just added another agent, PNC-27, to the growing list of drugs that falsely claim to treat or cure cancer.

An FDA lab recently found the bacteria Variovorax paradoxus in PNC-27, a product that is claiming to treat and cure all cancers, claiming to affect lung cancer as affectively as head and neck cancer. Though no illness or serious adverse events were reported to the FDA, contact with contaminated samples can lead to life-threatening infections, especially in vulnerable populations, such as young children, elderly people, pregnant women and people who have weakened immune systems, according to a statement released by the FDA.

“In general, consumers should be cautious of products marketed and sold online claiming to treat, cure or prevent any disease. Products claiming to treat, cure or prevent disease, but are not proven safe and effective for those purposes not only defraud consumers of money, they can lead to delays in getting proper diagnosis and treatment of a potentially serious condition,” Kristofer Baumgartner, FDA spokesperson, said in an interview with CURE.

PNC-27 is being dosed in multiple ways, such as a nebulized solution, intravenous solution, vaginal suppository or rectal suppository.

The FDA is urging people not to purchase or use PNC-27, which is neither FDA evaluated or approved. Patients should consult with their licensed health care providers before deciding on a treatment plan, and if they have already taken PNC-27, they should see their doctor as soon as possible, and report any adverse events to the FDA’s MedWatch Adverse Event Reporting Program.

As a matter of policy, the FDA cannot discuss any ongoing trials in detail, Baumgartner said. – See more at: http://www.curetoday.com/articles/fda-warns-against-socalled-cancer-cure#sthash.YgMC7JgV.dpuf

 

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

January, 2017|Oral Cancer News|

Why the FDA Wants More Control over Some Lab Tests

The FDA finds that many so-called laboratory-derived tests may actually harm patients

By Charles Schmidt | Scientific American December 2016 Issue

Every year in the U.S., doctor’s offices and hospitals order billions of laboratory tests to measure everything from cholesterol levels in the blood to the presence of a gene thought to increase the risk of developing Alzheimer’s disease. Physicians and patients typically assume that they can trust the results of these tests. And most of the time they can. But not all lab tests are equally reliable, and faulty ones can have serious consequences. Sometimes they fail to detect life-threatening conditions. Other times they indicate a problem that does not exist, which can lead to unneeded, perhaps even dangerous treatments.

Through a quirk of regulatory history, many such tests are not subject to the same medical standards as other tools used to identify risk for disease or to definitively diagnose a condition. These are called lab-developed tests, or LDTs, defined as tests that are manufactured and interpreted by the same individual lab that designed them—in contrast to, say, a quick strep test meant to be used and understood by a wide variety of personnel in doctor’s offices everywhere. Most people first encounter an LDT during a checkup when the physician is faced with a diagnostic dilemma that cannot be resolved by widely available blood tests.

The trouble is, experts believe many of these tests are not useful, and some may even cause harm by convincing too many people that they have a rare illness when they do not, diagnosing them with a condition that has so far not been shown to be harmful or reassuring them that they are healthy when in fact there is no scientifically credible way to know if that is indeed the case. “We tend to think of lab tests as being the ultimate truth,” says Ramy Arnaout, an assistant professor of pathology at Harvard Medical School. “But no test is 100 percent accurate, and some of these LDTs aren’t medically useful at all.”

The U.S. Food and Drug Administration is now taking steps to restore confidence in the reliability of lab-developed tests. In 2014 the agency released proposed guidelines that will subject the measures, for the first time, to federal oversight—including having to submit evidence of efficacy to it before the tests may be marketed. Although the FDA would not comment for this story, several industry sources believe the final rulings may begin taking effect soon, much to the chagrin of some lab directors who say that the requirements could boost costs and hinder medical practice.

Widening Loophole

Twenty-five years ago LDTs played too small a role in medical practice for the FDA to pay them much attention. Only a few—most notably Pap smears for the detection of cervical cancer—were widely used. FDA officials adopted a policy of “enforcement discretion,” which meant they pretty much left LDTs alone while they focused on tools with an apparently greater potential for harm, such as malfunctioning pacemakers.

After researchers developed new genetic engineering techniques in the 1990s, however, the possibilities for LDTs expanded dramatically. Whereas previous generations of LDTs looked for a handful of unusual proteins, for example, some of the newly emerging genetic tests could sort through any number of the three billion base pairs, or letters, of the DNA alphabet found in the human genome, looking for abnormalities related to disease. In addition, testing became automated, making LDTs increasingly easier to design and use.

The improved technology led to an enormous rise in the number and variety of LDTs that came to market. By some estimates, about 11,000 labs now offer between 60,000 and 100,000 of them; no one knows precisely how many because, of course, these tests do not have to be registered anywhere.

Under current federal regulations, LDTs enjoy a big loophole, which means they do not have to be evaluated for their medical usefulness. Nor are they required to have research about them made public. The lab that created them does need to meet certain fundamental standards of scientific practice. But the FDA does not vet the tests either before or after doctors can start ordering them for patients, as it does for most prescription drugs or medical devices.

This loophole means that companies ranging from small start-ups offering just one or two tests to much larger diagnostic labs that offer thousands of tests can develop and charge for new LDTs much more easily than they can for most other categories of medical products. With the rise in the number of tests has come a series of reports showing that certain ones have already hurt people by delivering misleading results.

Clinical Validity

The FDA has cited 20 different types of LDTs as especially troubling, including Lyme disease and whooping cough tests that regularly give wrong answers and LDTs that purport to determine a woman’s risk for ovarian cancer such as by measuring the presence of the protein CA 125 in the blood. In September the agency concluded that screening measures for this protein offered “no proven benefit” and warned physicians against recommending or using them.

Many of the tests that have raised the FDA’s ire may indeed measure what they claim to measure. The problem is that the measured substance may not be a good indicator of a specific medical problem. In the case of the ovarian cancer tests, for instance, high levels of CA 125, which is made in the ovaries, should in theory signify the presence of extra ovarian cells—in other words, the presence of a tumor. In reality, it turns out that many women with high levels of CA 125 do not have ovarian cancer, and, conversely, many women with cancer do not have high levels of CA 125. Thus, measures of CA 125 cannot be trusted to give an accurate diagnosis of cancer—and yet a number of women who tested positive apparently feared the possibility of cancer so much that they decided to have their healthy ovaries removed anyway.

One way that investigators determine whether a medical test should be used as a guide to a patient’s condition is by applying a somewhat obscure statistical ratio called a positive predictive value, or PPV. This measure takes into account just how common a condition might be in a given group of people.

Why such a consideration would be important in determining a test’s usefulness may be best understood by analogy. If you drop a baited hook into a barrel full of fish, the chances that a tug on the line means that you have caught a fish are pretty high. On the other hand, dropping the same baited hook into a freshwater lake that has not been stocked with fish makes it much less likely that any given tug on the line represents a fish, as opposed to, say, a tree snag. Because the barrel contains many more fish for a given volume of water than the lake does, a tug in the container has a PPV close to 100 percent, whereas that of a tug in an unstocked lake is much less than 100 percent.

This crucial statistical distinction explains the problem the FDA has with one current ovarian screening test, which its developer claimed had a PPV of 99.3 percent. Closer analysis by independent biostatisticians revealed, however, that the value was calculated on the basis of a single experiment in which half the patients were already known to have ovarian cancer—a highly selected group that is the medical equivalent of a stocked pond.

When the researchers recalculated the PPV using ovarian cancer’s true frequency in the general U.S. population of one case for every 2,500 postmenopausal women, the PPV plummeted to just 6.5 percent. In other words, only one in every 15 patients who received a positive result from this malignancy test would have actually had ovarian cancer. The other 14 would, if they had relied on this test alone, very likely have undergone unnecessary operations to remove their otherwise healthy ovaries because they would have mistakenly believed they had a 99.3 percent chance of having cancer.

Changing Focus

Because the FDA does not have the resources to oversee all the LDTs that have come to market in recent years, the agency plans to divide them into three categories, based on the likelihood that a misleading or incorrect result from a particular test could cause substantial harm. Under the new guidelines, LDTs would be considered high risk if inaccurate results could lead to death or prolonged disabilities. Such tests would come under the greatest inspection, information about them would need to be entered in a national database, and manufacturers would have to prove their safety and efficacy to the FDA before they could be sold. “Basically, the FDA wants to see the supporting evidence before it allows a high-risk LDT to go out on the market,” says Joshua Sharfstein, a physician and professor at the Johns Hopkins Bloomberg School of Public Health.

Even this targeted approach worries many industry leaders and some professional medical societies, including the American Medical Association. “It really depends on how the FDA chooses to define high risk, and that currently isn’t clear,” says Curtis Hanson, chief medical officer at Mayo Medical Laboratories in Rochester, Minn., which conducts 25 million lab tests a year. “High-risk tests could amount to between 1 and 10 percent of LDTs on the market today. How is the FDA going to review and find the rare cases where you have problems and do that in an efficient way that doesn’t slow progress?”

For patients and their physicians, the question is much more basic. Why should they ever have to wonder whether a commercially available medical test does more harm than good?

This article was originally published with the title “When Medical Tests Mislead”

 

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

November, 2016|Oral Cancer News|

Expert Asserts Pembrolizumab to Play Important Role in Head and Neck Cancer Treatment

Source: www.targetedonc.com
Author: Laura Panjwani

Joshua-Bauml

The FDA approval of pembrolizumab (Keytruda) as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in August 2016 was extremely significant for this patient population, which previously had limited options following progression on a platinum-based chemotherapy.

The approval was based on the phase Ib KEYNOTE-012 study, which demonstrated that pembrolizumab had an overall response rate (ORR) of 18% and a stable disease rate of 17% in patients with recurrent/metastatic HNSCC.

Several other studies are further evaluating the immunotherapy agent in HNSCC.Preliminary results of the phase II KEYNOTE-055 study—which included 92 evaluable patients who received pembrolizumab after failing platinum and cetuximab therapies—were presented at the 2016 ASCO Annual Meeting.

In an interview with Targeted Oncology, lead study author Joshua M. Bauml, MD, an assistant professor of Medicine, Hospital of the University of Pennsylvania and the Veteran’s Administration Medical Center, discusses the impact of pembrolizumab’s success in HNSCC, the results of the KEYNOTE-055 study, and what he sees on the horizon for the PD-1 inhibitor in this field.

TARGETED ONCOLOGY: What role do you envision pembrolizumab having in this patient population?

Baumi: It is going to play a critical role in head and neck cancer. The other agents that are available have limited efficacy, and are associated with significant toxicities. This is a clear improvement for our patient population with limited options.

TARGETED ONCOLOGY: What were the key takeaways from KEYNOTE-055? Baumi: Patients with recurrent/metastatic head and neck cancer that is refractory to both platinum-based therapy and cetuximab (Erbitux) really have very few options. The historical reference population we usually use is patients treated with methotrexate, which has a response rate of 5% and an overall survival (OS) of only about 6 months. There is a really great need for this. For pembrolizumab, which is an anti–PD-L1 agent, there is biologic rationale to think that it would be active in this patient population. PD-L1 and PD-L2 are unregulated in head and neck cancer.

What KEYNOTE-055 did is really try and create a homogenous patient population. Rather than a large phase I study, here are patients all who have failed both platinum-based therapy and cetuximab. We have really identified the sickest patient population.

What we are able to show in this study was that the drug was well tolerated and it has a response rate of 17% to 18%, which compares favorably for the 5% seen with the prior data with methotrexate. The OS rate was 8 months, which again compares very favorably to the 6 months seen with methotrexate. This was true, even though 85% of patients had received at least 2 prior treatments for head and neck cancer.

TARGETED ONCOLOGY: What did this study tell us about the safety of pembrolizumab in head and neck cancer?

Baumi: The rate of grade 3 through 5 treatment-related adverse events was 12% in our study. Nearly all of the side effects are what you would expect with pembrolizumab; those have been reported in multiple other studies. There was 1 treatment-related death due to pneumonitis, which is a rare side effect of this class of drugs.

Outside of that, it was a really well-tolerated agent. The fact that if you compared grade 3 through 5 toxicities of 12% with cytotoxic chemotherapy, this is a very well-tolerated agent.

TARGETED ONCOLOGY: How common is it for patients to fail both platinum-based therapy and cetuximab?

Baumi: Any patient who has recurrent or metastatic head and neck cancer is going to go through these agents if they survive long enough to get them. Basically, we know that these are the limited tools in our toolbox. We have platinum, we have cetuximab, and then we are really out of options. Many patients have received cetuximab in the locally advanced setting and so we have already lost one of our active treatments. This affects a lot of people.

TARGETED ONCOLOGY: What is next for pembrolizumab in head and neck cancer?

Baumi: There are currently phase III studies evaluating pembrolizumab in head and neck cancer both in combination with and versus traditional cytotoxic chemotherapy to see if we can move up the treatment earlier for patients. The key difference between pembrolizumab and cytotoxics is beyond the improved safety profile. However, we have durable responses; 75% of those patients who responded are still responding to this day. That is really not something that we see.

TARGETED ONCOLOGY: What are the biggest questions that remain regarding the treatment of patients with metastatic head and neck cancer?

Baumi: One of the key questions that relates to immunotherapy—and this covers all tumors—is trying to identify who the 20% of patients are that will respond. Eighty percent of our patients are not responding to our therapies.

Identifying a biomarker to enrich this patient population is very critical. Right now, I would not select patients for pembrolizumab by virtue of PD-L1 status because there were responses in the PD-L1–negative cohorts.

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

September, 2016|Oral Cancer News|

Expert says Nivolumab Poised to Change Standard of Care in SCCHN

Source: www.onclive.com
Author: Laura Panjwani

Robert-Ferris

Nivolumab (Opdivo) is a game-changing agent for the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN), according to Robert L. Ferris, MD, PhD.

“Recent findings have shown us that this agent is really the new standard-of-care option for all platinum-refractory patients with head and neck cancer,” says Ferris, vice chair for Clinical Operations, associate director for Translational Research, and co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. “This is regardless of whether patients are PD-L1–positive or negative or whether they are HPV-positive or negative.”

The PD-L1 inhibitor received a priority review designation by the FDA in July 2016 based on the CheckMate-141 study, which demonstrated a median overall survival (OS) with nivolumab of 7.5 months compared with 5.1 months with investigator’s choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P = .0101) in patients with recurrent or metastatic SCCHN.

The objective response rate (ORR) was 13.3% with nivolumab and 5.8% for investigator’s choice. The FDA is scheduled to make a decision on the application for the PD-1 inhibitor by November 11, 2016, as part of the Prescription Drug User Fee Act.

Ferris was the lead author on an analysis that further evaluated preliminary data from CheckMate-141, which was presented at the 2016 ASCO Annual Meeting. In an interview with OncLive, he discusses the findings of this study, potential biomarkers for nivolumab, and questions that remain regarding the use of the immunotherapy in SCCHN.

OncLive: What were the updated findings from CheckMate-141 presented at ASCO?

Ferris: The data that were presented at the 2016 ASCO Annual Meeting were further evaluations and follow-up on some preliminary data—originally presented at the 2016 AACR Annual Meeting—that listed the OS results.

At ASCO, we recapped the primary endpoint of OS as an important endpoint for immunotherapies because response rate and progression-free survival may not be as accurate. Ultimately, the FDA and people at large want OS. In this study, OS was 36% at 1 year in the nivolumab-treated arm and 16.6% in the comparator arm, which was investigator’s choice of single-agent chemotherapy, consisting of methotrexate, docetaxel, or cetuximab. In this phase III randomized trial, nivolumab was given in a 2:1 randomization: 240 patients received nivolumab and 120 received investigator’s choice.

Also at ASCO, we presented further evaluations consisting of what the regimens are in the comparator arm. There was about 20% each of docetaxel and methotrexate and 12% of cetuximab. Approximately 60% of the patients had prior cetuximab exposure and we stratified by cetuximab as a prior therapy. We also demonstrated the ORR, which was 13.3% in the nivolumab-treated arm versus 5.8% in the investigator’s choice arm.

Therefore, there was an improvement in overall response, but the difference seemed more modest than the OS benefit—which was a doubling—with 20% more patients alive at 1 year. This reinforces the concept that perhaps response rate may not be the best endpoint. Progression-free survival (PFS) was double at 6 months, with about 20% in the nivolumab arm versus about 9.9% in the investigator’s choice arm. The median PFS was not different, but the 6-month PFS was twice as high. The time to response was about 2 months in each arm at the first assessment.

Your analysis also looked at biomarkers. Can you discuss these findings and their significance?

The p16 or HPV-positive group had a better hazard ratio for OS than the overall study population. The hazard ratio was .73 for the overall population, using a preplanned interim analysis. With the HPV-positive group, we had a hazard ratio of .55 and the HPV-negative group had a hazard ratio of .99. It is still favoring the nivolumab-treated patients but, with the curves separated earlier in the HPV-positive group, one could see the improvement with nivolumab at about 1 to 2 months. It took 7 or 8 months with the HPV-negative group to show a separation of the curves in favor of nivolumab.

We looked at PD-L1 levels, and PD-L1—using a 1% or above level—had an improvement in the PD-L1–positive patients in favor of nivolumab in terms of OS and ORR. When we looked at 5% and 10% thresholds of PD-L1, the OS did not seem to improve. Therefore, in all levels above 1%, the OS was similarly beneficial over the PD-L1 less-than-1% group. However, essentially all levels of PD-L1–positivity and PD-L1–negativity still favored nivolumab, but the benefit was more when its levels were greater than 1%.

We could combine HPV status with PD-L1 status and look at subsets; however, essentially every subset benefited, whether it was PD-L1–negative or positive. This indicates that, in this group of patients, who progress within 6 months of platinum-based therapy, that no current systemic therapeutic options benefit patients as well as nivolumab.

With regard to these findings, what are you most excited about?

Head and neck cancer is a difficult disease. Until recently, we didn’t know the impact of this enrichment for HPV-positive virus-induced subsets and we didn’t know if this was an immune responsive cancer. Clearly, it is. We have all of the hallmarks that we have seen for a bright future—based on the melanoma data—and a series of other cancers indicating response rates in the 15% to 20% range, suggesting that we now have a platform of the PD-1 pathway to combine with other checkpoints and to integrate earlier in disease with radiation and chemotherapy.

We have a demonstration of head and neck cancer as an immune-responsive cancer. We are beginning to get an idea of the biomarkers and starting to be able to segment patients who will benefit. Now, we have a large comparative trial with an OS endpoint and tissue to look at biomarkers to try and understand what the best future combinations will be.

What are some questions that you still hope to answer regarding nivolumab in head and neck cancer?

We have to get down deeper into the nonresponders. We should acknowledge that the majority of patients neither had a response nor benefited. Understanding who is more likely to benefit is useful, but we also need to understand the levels of alternative checkpoint receptors or other biomarkers of resistance.

We have sequential lymphocyte specimens from the peripheral blood, tissues, and serum so those are intensively under evaluation. There are interferon gamma signatures that have risen from the melanoma checkpoint field that will certainty be applied, as well.

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

August, 2016|Oral Cancer News|

Merck Says FDA Accepts Its SBLA For Keytruda For Treatment Of Head & Neck Cancer

Source: www.finchannel.com
Author: Fin Channel News Editorial Staff
 
mercke1423056380602

The FINANCIAL — Merck, known as MSD outside the United States and Canada, on April 13 announced that the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental Biologics License Application (sBLA) for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

The application is seeking approval for KEYTRUDA as a single agent at a dose of 200 mg administered intravenously every three weeks. The FDA granted Priority Review with a PDUFA, or target action, date of Aug. 9; the sBLA will be reviewed under the FDA’s Accelerated Approval program, according to Merck.

“Starting in the early days of our development program, we have explored the role of KEYTRUDA for patients with head and neck cancer, a difficult-to-treat and debilitating disease with very few treatment options,” said Roger Dansey, M.D., senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “We are encouraged by the data emerging from our program in this type of cancer, and welcome today’s news as this is an important step toward making KEYTRUDA available to these patients.”

Merck currently has the largest immuno-oncology clinical development program in head and neck cancer and is advancing multiple registration-enabling studies with KEYTRUDA as a single agent and in combination with chemotherapy.

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

April, 2016|Oral Cancer News|

Nivolumab Could Change Head and Neck Cancer Treatment Paradigm

Source: www.Targetedonc.com
Author: Laura Panjwani
 

“To have an anti–PD-1 agent be proven to improve survival in head and neck cancer in a randomized phase III trial, and the potential for a new FDA approval in the near future is a game changer.” – Robert Ferris, MD, PhD

With the phase III CheckMate-141 trial being stopped early due to the anti–PD-1 agent nivolumab having met its primary endpoint of overall survival improvement in head and neck cancer, Robert Ferris, MD, PhD, couldn’t be more elated.

“This is what I’ve devoted my career to, and it is gratifying to see that really come to pass,” said Ferris, professor and chief, Division of Head and Neck Surgery, vice chair for Clinical Operations, associate director for Translational Research, and coleader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute, in an exclusive interview with Targeted Oncology.

“To have an anti–PD-1 agent be proven to improve survival in head and neck cancer in a randomized phase III trial, and the potential for a new FDA approval in the near future is a game changer. There is now hope for a lot of patients and physicians who have been frustrated by this difficult-to-treat disease. This opens up a whole new class of therapies for this population.”

Ferris, who acted as cochair/coprimary investigator for the trial alongside Maura Gillison, MD, PhD, Ohio State University, said the trial pitted nivolumab against the investigator’s choice of cetuximab (Erbitux), methotrexate, or docetaxel in patients with platinum-refractory squamous cell carcinoma of the head and neck (SCCHN).

Eligible patients who are still enrolled in the study are now able to continue their current treatment regimen, or switch over to nivolumab. Ferris says the prospect of having a new drug available for SCCHN is exciting, especially considering the last FDA approval for the disease type came in 2006.

“It was 2006 when cetuximab was approved and that was a relatively modest advance, although it was the first targeted therapy. We have a population without any other therapeutic options and a very rapid progression,” he said.

“Anti–PD-1 agents have had promising data in melanoma and squamous non–small cell lung cancer (NSCLC). Squamous NSCLC genomically resembles HPV-negative head and neck cancer in its behavior regarding carcinogen exposure. Therefore, we felt it might respond well to anti–PD-1 agents, too. We designed the study to hopefully create something new and effective for an essentially hopeless palliative group of patients.”

The phase III data have not yet been released from the trial, though early discontinuation has generated significant excitement in the field. The trial was scheduled to run until October 2016, has generated significant excitement in the field, says Ferris, who is a primary author on the abstract submitted for presentation at the ASCO Annual Meeting.

Ferris says the study was designed reflect the idea that there are different standards of care for SCCHN throughout the world, which is why cetuximab, methotrexate, or docetaxel were chosen for the control arms.

“We still don’t have public data for what all of the standard of care selections were, but we do know that cetuximab tends to be used more in North America. Meanwhile, the other 2 agents are more likely to be used in Europe and other countries because cetuximab is not approved there,” he said.

“The benefits are really very modest with those single-agent treatments and they are toxic. There is very much a need for a new treatment. We are very interested in the toxicity profile of nivolumab, as it has proven to be well tolerated in other cancers.”

Ferris adds that the excitement generated in the field stems from the revelation of efficacy for pembrolizumab (Keytruda) at the 2015 ASCO Annual Meeting, saying the data from both pembrolizumab and nivolumab “appear to be very similar.”

“There was a suspicion that nivolumab would be promising in head and neck cancer, as well. There is a great deal of buzz from medical oncology leaders all over the country regarding this. People have really been waiting with bated breath for something for our patients. This is a real win for the community and for a population of patients with a devastating disease in a very important area of the body,” he said.

“This disease can disrupt speaking, drinking, swallowing, and has catastrophic consequences. I expect enthusiasm and support from the community regarding this.”

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

February, 2016|Oral Cancer News|

NCI-designated Cancer Centers Urge HPV Vaccination for the Prevention of Cancer

Source: www.medicine.wustl.edu
Author: Washington University School of Medicine in St. Louis Staff
 

Approximately 79 million people in the United States are currently infected with a human papillomavirus (HPV) according to the Centers for Disease Control and Prevention (CDC), and 14 million new infections occur each year. Several types of high-risk HPV are responsible for the vast majority of
cervical, anal, oropharyngeal (middle throat) and other genital cancers. The CDC also reports that each year in the U.S., 27,000 men and women are diagnosed with an HPV-related cancer, which amounts to a new case every 20 minutes. Even though many of these HPV-related cancers are preventable with a safe and effective vaccine, HPV vaccination rates across the U.S. remain low.

Together we, a group of the National Cancer Institute (NCI)- designated Cancer Centers, recognize these low rates of HPV vaccination as a serious public health threat. HPV vaccination represents a rare opportunity to prevent many cases of cancer that is tragically underused. As national leaders in cancer research and clinical care, we are compelled to jointly issue this call to action.

According to a 2015 CDC report, only 40 percent of girls and 21 percent of boys in the U.S. are receiving the recommended three doses of the HPV vaccine. This falls far short of the goal of 80 percent by the end of this decade, set forth by the U.S. Department of Health and Human Service’s Healthy People 2020 mission. Furthermore, U.S. rates are significantly lower than those of countries such as Australia (75 percent), the United Kingdom (84-92 percent) and Rwanda (93 percent), which have shown that high vaccination rates are currently achievable. The HPV vaccines, like all vaccines used in the U.S., passed extensive safety testing before and after being approved by the U.S. Food and Drug Administration (FDA). The vaccines
have a safety profile similar to that of other vaccines approved for adolescents in the U.S. Internationally, the safety of HPV vaccines has been tested and approved by the World Health Organization’s Global Advisory Committee on Vaccine Safety. CDC recommends that boys and girls receive three doses of HPV vaccine at ages 11 or 12 years. The HPV vaccine series can be started in preteens as early as age 9 and should be completed before the 13th birthday. The HPV vaccine is more effective the earlier it is given; however, it is also recommended for young women until age 26 and young men until age 21.The low vaccination rates are alarming given our current ability to safely and effectively save lives by preventing HPV infection
and its associated cancers. Therefore, we urge parents and health care providers to protect the health of our children through a number of actions:

  • We encourage all parents and guardians to have their sons and daughters complete the 3-dose HPV vaccine series before the 13th birthday, and complete the series as soon as possible in children aged 13 to 17. Parents and guardians should talk to their health care provider to learn more about HPV vaccines and their benefits.
  • We encourage young men (up to age 21) and young women (up to age 26), who were not vaccinated as preteens or teens, to complete the 3-dose HPV vaccine series to protect themselves against HPV.
  • We encourage all health care providers to be advocates for cancer prevention by making strong recommendations for childhood HPV vaccination. We ask providers to join forces to educate parents/guardians and colleagues about the importance and benefits of HPV vaccination. HPV vaccination is our best defense in stopping HPV infection  in our youth and preventing HPV-related cancers in our communities. The HPV vaccine is CANCER PREVENTION. More information is available from the CDC.

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

 

February, 2016|Oral Cancer News|

FDA Clears First Tobacco Product for Marketing

For the first time since it was given the power to regulate tobacco, the US Food and Drug Administration (FDA) has authorized marketing of a new product.

The agency said that eight new smokeless snus products, to be sold in the United States under the “General” brand name by Stockholm-based Swedish Match AB, are now authorized under the premarket tobacco application pathway, which was established by the 2009 Family Smoking Prevention and Tobacco Control Act. Snus cannot be marketed as “FDA-approved,” however.

“Today’s action demonstrates that the premarket tobacco application process is a viable pathway under which products can be marketed, as long as the public health can be protected,” said Mitch Zeller, director of the FDA’s Center for Tobacco Products, in a statement.

This is the first time any tobacco maker has completed the rigorous premarket tobacco application review process at the agency; others have had products approved by proving they are substantially equivalent to what is already on the market.

The agency said that Swedish Match provided evidence that “these products would likely provide less toxic options if current adult smokeless tobacco users used them exclusively.” The agency also agreed with the company that snus’ availability would not result in substantial new use, delay quit attempts, or attract ex-smokers.

Swedish Match had been seeking separately to remove warnings that snus is harmful, but the agency has not yet ruled on that request.

In that separate application, Swedish Match was seeking to have the 10 types of snus it already sells in the United States designated as modified-risk tobacco products. The agency accepted the company’s application in August 2014 and held a meeting of its advisory panel to review the evidence in April 2015.

The company wanted to remove warnings that snus could cause gum disease and tooth loss or mouth cancer. It also sought to label its products with the statement that reads, “No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes.” The advisory committee could not reach consensus on whether snus was a safer alternative to smoking, and also was not convinced that the product would not attract new users. At that meeting, Dennis Henigan, director of legal and policy analysis for the Campaign for Tobacco-Free Kids, said Swedish Match had failed to show that users would not use both cigarettes and snus, or that young people would not initiate use.

Snus, which is ground tobacco, salt, and water, comes in a pouch that users place under their upper lip. It can be used for up to 30 minutes, according to the company. It is popular in Sweden, but less so in the United States. Swedish Match says its General brand accounts for 11% of American convenience store snus sales. The 60 million cans it sells annually in the United States are dwarfed by the billion cans of smokeless tobacco sold.

The Centers for Disease Control and Prevention estimates that less than 4% of adults use smokeless tobacco, with rates highest among men aged 18 to 25 years (10%). A 2014 Centers for Disease Control and Prevention survey of high school students found that 5.5% of overall used smokeless tobacco, and an additional 1.9% reported current use of snus.

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

November, 2015|Oral Cancer News|