Ovarian Cancer Could Be Next Application For CAR T-Cell Therapy

Ovarian Cancer Could Be Next Application For CAR T-Cell TherapyWhile CAR T-cell therapy has been proven to work for liquid—or blood—cancers, the challenge has been to apply this technology to solid tumors. That’s why Amit Kumar, PhD, president and CEO at ITUS Corporation, a San Jose, California-based cancer-focused biotechnology company, is working with researchers at Moffitt Cancer Center to determine if this therapy can be beneficial to women with ovarian cancer.

Managed Healthcare Executive (MHE) recently talked to Kumar to learn how this technology works and about the promise it holds for women diagnosed with ovarian cancer.

MHE: Tell us about using CAR T therapy for ovarian cancer and the promise it holds.
Kumar:  The reason CAR T-cell therapy works for liquid—or blood—cancers is you can engineer T cells to go after a protein called CD19 on the surface of B cells. That has been very successful with two products already approved—with Yescarta from Kite Pharma and Kymriah from Novartis Pharmaceuticals—and several products being developed in clinical trials.
In solid tumors, such as ovarian cancer, there hasn’t been any demonstration of efficacy. One of the challenges has been that it’s hard to find a target protein on the surface of solid tumors that doesn’t exist anywhere else on healthy tissue.

MHE: How could your approach help with cancer treatment?
Kumar: Our technology, which we’ve licensed from the Wistar Institute, has identified a specific protein that fits that characteristic. That means that on ovarian cells in adult women the specific receptor—or protein—that we’re targeting with our engineered T cells is called the follicle stimulating hormone receptor. This is a protein that’s found only on ovarian cells in adult women. By targeting that protein, we’re not going to have our T cells target any healthy tissue.
With our CAR T, an antibody fragment binds to the receptor—that’s where we put the follicle stimulating hormone. That’s why we think this is going to be a very positive approach to the solid tumor model, which ovarian cancer is.

MHE: Could this method of treatment be used to treat other types of cancer?
Kumar: In addition, and this is at some point in the future, there are indications that the follicle stimulating hormone receptor is found on the blood vessels of other tumors, so blood vessels that are supplying nutrients to tumors of the prostate, pancreas, and lungs.
If this therapy works on ovarian cancer, we think it has a good opportunity to work on a number of other cancers as well

MHE: How did you gain access to this technology that you’d like to use to treat ovarian cancer?
Kumar: We’re licensing this technology from the Wistar Institute, where the technology was developed through funding from the U.S. National Institutes of Health and other agencies. Now, we’re taking that technology over to the Moffitt Cancer Center, which is one of the top cancer centers in the United States and in the top five in the area of CAR T technology. They’ve invested in a tremendous amount in infrastructure to do the preclinical work as well as the clinical work on CAR T technology.
We’re going to do a sponsored research agreement, which means we’re going to fund the research there. Their researchers are going to do the work; we’re going to access all of their infrastructure, as well as the top scientists and physicians in the country that are working on CAR T.

It will cost us a little over a million dollars to do this research project that we hope will enable us to take this technology into the clinic, into clinical testing.

MHE: Who’s leading the research team that’s studying this? 
Kumar: The lead researcher is Jose Conejo-Garcia, MD, PhD, who’s a co-inventor of the technology from his time as a professor at Wistar. A little over a year ago, he moved to the Moffitt Cancer Center and is now going to take the lead on getting this technology into human trials.

MHE: Where is this treatment for ovarian cancer in its journey?
Kumar: It’s still in the preclinical stage. Conejo-Garcia and his team have published the data on this technology in mouse models, demonstrating the efficacy of this technology to treat ovarian cancer. The plan at Moffitt Cancer Center is to complete Investigational New Drug (IND-) enabling studies. We have to complete those studies, which include a toxicity study, that then we will submit to the FDA; we expect that the FDA will approve taking this to the next step, which is into human testing.

We anticipate it will take us about 18 to 24 months to complete the IND-enabling studies, which will then be submitted to the FDA. Subsequent to that, we expect to work with human ovarian cancer patients. This will most likely be refractory patients—or patients who have had every other approved therapy attempted and really don’t have much hope.

We’d like to have this treatment available for women in clinical trials by the middle to the end of 2019. Depending on how well those clinical trials and the FDA approval process go, we anticipate probably another year to two years for this therapy to be generally available. We’re still looking at three to four years at least before it becomes a product.

To read this entire article by Managed Healthcare Executive, please click here.

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Future Focus: Ovarian Cancer in 2018 and Beyond

Oliver Dorigo, M.D., Ph.D., Associate Professor of Obstetrics and Gynecology (Oncology), Stanford University Medical Center, talks about the direction of research in the ovarian cancer field going into 2018 and beyond. He shares his excitement about trials that will further investigate the efficacy of PARP inhibitors, and focus on immunotherapy. He speaks with enthusiasm about the potential to “engineer immunity” by taking a person’s T-cells and redirecting them against tumor tissue.

Dorigo emphasizes the need for better diagnostic tools to detect ovarian cancer. “The survival rate in Stage 1 ovarian cancer, those cancers confined to the ovary, is over 90 percent,” he said. “If we can find technologies that allow us to find those ovarian cancers early on, I think we will make a huge step forward.”

To view this video and commentary on Oncology Nursing News, please click here.

How To Spot Ovarian Cancer Early? Dallas Researchers Have New Hope For Tests

How To Spot Ovarian Cancer Early? Dallas Researchers Have New Hope For TestsWhile modern medicine has made great strides in cancer treatment, ovarian cancer remains a stubborn killer. Researchers at UT Southwestern Medical Center in Dallas are hoping to help improve the odds.

Ovarian is the 10th most common cancer, but ranks fifth in cancer deaths, killing more women than any other gynecologic cancer. The key reason: Doctors have no reliable way to detect the cancer early.

Some 22,000 women are diagnosed annually with ovarian cancer, and “the majority of cases are detected in the latest stages of disease,” according to Dr. Jayanthi Lea, associate professor of obstetrics and gynecology at UT Southwestern.

Debbie Miller of Red Oak, an ovarian cancer survivor, puts it this way: “This disease is sneaky and deadly.”

Difficult to Detect

When detected before the cancer has spread outside the ovary, the five-year survival rate is more than 90 percent, according to the American Cancer Society. But only about 1 in 5 ovarian cancer patients are diagnosed in these early stages. By comparison, some 60 percent of breast cancer patients are diagnosed early, thanks to mammograms and increased awareness.

Most women with ovarian cancer have no symptoms, or if they do, the symptoms are easy to ignore. Miller, 65, of Double Oak, was diagnosed in 2006 by accident, when she was hospitalized for a pulmonary embolism. Scans turned up a tumor in her abdomen.

Miller had been needing to urinate frequently, a symptom of ovarian cancer, but had chalked it up to normal aging.

“It wasn’t even bothersome enough to report to the doctor,” she said. “And what 55-year-old woman doesn’t experience that?”

Better Detection Tools

To help arm doctors with better tools of detection, UT Southwestern is part of a nationwide clinical trial evaluating a blood test that could detect ovarian cancer earlier in healthy, post-menopausal women.The test looks at levels of CA-125, a protein that can signal the presence of ovarian cancer.

That’s the same CA-125 test that was essentially discredited as a routine screening tool in recent years. In 2012, the U.S. Preventive Services Task Force recommended against testing CA-125 levels in women with no symptoms, because a significant number of women experienced false-positive test results, risking unnecessary surgery.

The new research aims to develop an algorithm that would point to trends in CA-125 levels that might offer a more reliable way of diagnosing the disease. If the research results pan out as hoped, post-menopausal patients could get the blood test as part of their yearly physicals, and results would be followed year-after-year.

“Our thinking is, if we can look at the numbers over time, ideally we could catch the disease sooner rather than later, and that will improve the chances of survival for a lot of women,” said Dr. Matthew Carlson, assistant professor of obstetrics and gynecology at UT Southwestern and the principal investigator for the trial.

In addition, Alan Schroit, professor of immunology at UT Southwestern, is studying another possible avenue for early detection that’s promising so far. In a small study, he worked with Lea, who provided 40 blood samples from her patients with ovarian tumors who were scheduled for diagnostic surgery. Schroit’s team performed an ultra-sensitive test for the presence of particles secreted by malignant tumors in the blood samples.

“We were able to predict whether each patient had a benign or malignant tumor, with 100 percent accuracy,” Schroit said. After that group of patients underwent surgery or chemotherapy, the same test was performed on a second set of blood samples, and accurately predicted which patients had a recurrence.

“We’re confident we can detect early disease, and hopefully, this will turn into a routine screening test,” Schroit said. He’s working now to launch larger-scale studies.

 

To read this entire article by DallasNews.com, please click here.

 

Health Matters: Testing Your Genes for Cancer

Health Matters: Testing Your Genes for CancerWhether you’ve already been diagnosed, or you want to know your risk, health experts can test your DNA to determine your chances of developing cancer.

“The testing itself determines whether or not they have inherited this broken gene that could cause potentially a higher risk for developing these cancers,” said clinical nurse specialist Mary Ann Orlang.

Cancers, like, breast, ovarian, colon, and pancreatic, can all be detected early through a genetic cancer screening. “If a person carries a broken gene, their risk for breast cancer, if they carry for example, can be as high as 87 percent,” said Orlang.

First, health experts sit down with patients to review their medical history and their family’s medical history, including their mom, dad, grandparents, siblings, and aunts and uncles. Then they do a blood test to check their DNA. “Depending on which gene they carry, would determine the percentage of risk for developing a certain cancer in their lifetime,” said Orlang.

The blood test will examine the patient’s DNA to check for any genes that could have mutated, then telling the health expert which cancer the patient is at risk for.

“If a patient did come back with a BRCA gene mutation, I talk to them about doing breast exams, self-breast awareness, and I talk to them about their options for risk–reducing mastectomy,” said Orlang.

The genetic test can also help doctors determine further surveillance for the patient. For example, patients with the BRCA gene not only have a higher breast cancer risk, they also have a higher ovarian cancer risk. “Knowing your risk would give you the knowledge to do some proactive things, active surveillance,” said Orlang.

Depending on a patient’s lifestyle, diet, and exposure, patients can test negative for the cancer genes and still develop cancer. However, having the gene doesn’t mean the patient will get cancer. It means they are at a higher risk and can take measures to prevent a cancer diagnosis.

To read this entire article on NBC 2, please click here.

Clovis’ Rubraca Takes Aim At Lynparza, Zejula With Priority Review For New Use

Clovis' Rubraca Takes Aim At Lynparza, Zejula With Priority Review For New UseClovis Oncology is one step away from a new use for its ovarian cancer drug Rubraca—and with FDA priority review, it could take that step early next year.

The drug, launched less than a year ago as a third-line treatment for BRCA-positive ovarian cancer, is up for a new approval as a maintenance therapy in women with recurrent disease who’ve responded, at least partially, to platinum chemotherapy. And that’s all women, not just those who’ve tested positive for BRCA mutations.

Of course, that’s up to the FDA and its decision, which the agency has deadlined on April 6. And if the FDA does give its blessing, Clovis won’t be alone in the ovarian cancer maintenance field—AstraZeneca’s Lynparza and Tesaro’s Zejula both are approved for the same use.

But analysts see the market for maintenance use of these drugs, which are all PARP inhibitors, as a $2 billion opportunity, leaving room for all three to nab significant sales in the indication. Even as the third in the class to win this particular approval, the Clovis therapy would be “very well positioned to capture market share in the large second-line maintenance category pending approval … based on strong Ariel3 trial results,” Leerink analyst Michael Schmidt said in a Wednesday note.

Lynparza was the first PARP drug to hit the scene, back in 2014, with Rubraca following last December and Zejula in May 2017. They’re the first new drugs for ovarian cancer in more than a decade, and they’ve already transformed its treatment for many women.

And the way Clovis sees it, there’s an advantage built into the Ariel3 trial data that makes up its application for the new Rubraca use. Unlike some other PARP studies, Ariel3 didn’t limit itself to patients who’d responded completely to platinum chemo. Two-thirds of the participants had only achieved a partial response to chemo, and so investigators could monitor residual tumors to see whether Rubraca could improve on that initial response—and it did, Clovis CEO Patrick Mahaffey said in an interview ahead of the data release this fall.

Among BRCA-positive patients, 38% showed a treatment response, and 18% saw their residual tumor disappear, Mahaffey said. “What we see with Rubraca is a much more pronounced benefit,” he said in an interview at the time.

“The drug didn’t just maintain the original response, but we can improve on that original response,” he added. “Women are acutely aware of the risk and, sadly, the likelihood that the tumor will re-emerge. To be able to tell a patient, you have less tumor now than when you thought you had achieved a benefit from platinum chemotherapy—that is extraordinary.”

Clovis is pushing its Rubraca research forward in other cancers, too, notably prostate and breast cancers, with a pivotal prostate cancer trial expected to read out in the first half of next year. Clovis also has a partnership with Bristol-Myers Squibb to study Rubraca alongside the Big Pharma’s immuno-oncology star Opdivo.

To read this full article on Fierce Pharma, please click here.

Immunovaccine’s Incyte-Partnered Cancer Vaccine Shows Early Promise In Ovarian Cancer

Immunovaccine’s Incyte-Partnered Cancer Vaccine Shows Early Promise In Ovarian CancerImmunovaccine’s lead cancer vaccine, DPX-Survivac, combined with Incyte’s IDO1 enzyme inhibitor epacadostat and chemo cyclophosphamide, showed some early promise in advanced ovarian cancer.

According to early results from a phase 1b study, three of the 10 patients treated with the combination therapy achieved partial responses with a greater than 30% decrease in tumor size, whereas four patients’ disease isn’t significantly getting worse or better. Two patients who completed one year of treatment still had responses ongoing.

Blood tests also showed that most patients have exhibited targeted T-cell activation, which is linked with tumor regression.

Immunovaccine CEO Frederic Ors interpreted these early results as promising. “We are excited by the potential of DPX-Survivac to increase the number of individuals who may benefit from novel combination immunotherapies, and look forward to our continued work with Incyte and our other partners to increase the treatment options for such patients,” he said in a statement.

Based on the vaccine company’s DepoVax platform that allows freeze-dried vaccines to be reconstituted in oil, DPX-Survivac targets survivin, a cancer stem cell antigen and biomarker of cancer progression. Immuovaccine has also paired it with Merck’s Keytruda plus cyclophosphamide in ovarian cancer and is testing the vaccine platform as part of combo therapies for diffuse large B-cell lymphoma.

Immunovaccine’s goal with DPX-Survivac’s two early programs, however, is to confirm its ability to increase the vulnerability of hard-to-treat tumors. The company said that the survivin target is currently associated with over 20 types of solid and hematological cancers.

Incyte and Merck are also experimenting with the IDO1/PD-1 combo. Although the method delivered an excellent overall response rate in non-small cell lung cancer, its 8% ORR for ovarian cancer was unimpressive at best.

Tesaro’s Zejula and AstraZeneca’s Lynparza aside, even on the cancer vaccine front, Immunovaccine’s candidate is not the sole player in the recurrent ovarian cancer realm.

TapImmune’s lead candidate, TPIV200, a multiple-epitope anti-folate receptor alpha (FRα) immunotherapy, with an FDA orphan drug designation, has paired up with AstraZeneca’s checkpoint inhibitor Imfinzi in platinum-resistant ovarian cancer patients. What’s more, in order to tap a larger patient base, TapImmune has also initiated a phase 2 trial that focuses the vaccine as a maintenance therapy in women with late-stage ovarian cancer who are in remission, and it has been fast-tracked by the FDA for that usage.

According to TapImmune’s third-quarter update, the AZ-partnered phase 2 combo study will have preliminary results with tumor response data on the first 27 patients in the first half of 2018, and an interim futility analysis from the platinum-sensitive maintenance trial is expected in early 2019.

To read this full article on Fierce Pharma, please click here.

Tumor Profiling Panel Undergoes Simultaneous FDA, CMS Review

Tumor Profiling Panel Undergoes Simultaneous FDA, CMS ReviewThe US Food and Drug Administration (FDA) has approved a cancer diagnostic test, FoundationOne CDx (F1CDx, Foundation Medicine), for use in detecting 300-plus genetic mutations in any solid tumor. At the same time, the Centers for Medicare & Medicaid Services (CMS) proposed coverage of the test.

The simultaneous review by the two agencies took place under the Parallel Review Program, which “facilitates earlier access to innovative medical technologies,” the FDA said in a press statement.

This is only the second time that an in vitro diagnostic test has been approved and covered in this streamlined manner.

The F1CDx was also granted a “Breakthrough Device” designation, which was recently established under the 21st Century Cures Act, because it potentially consolidates multiple other companion diagnostic tests in a single test. That designation resulted in an accelerated 6-month review by the FDA.

“The F1CDx can help cancer patients and their health care professionals make more informed care decisions without the often invasive process of extracting tumor samples multiple times to determine eligibility for a single treatment or enrollment in a clinical trial,” said Jeffrey Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, in a press statement. “With the run of one test, patients and health care professionals can now evaluate several appropriate disease management options.”

According to the FDA, the F1CDx can identify which patients with any of five tumor types (non-small cell lung cancer, melanoma, breast cancer, colorectal cancer, or ovarian cancer) may benefit from 15 different FDA-approved mutation-targeted treatment options.

Hence, this next-generation sequencing–based test, which potentially detects 324 genetic mutations and 2 genomic signatures, moves beyond the previous “one test for one drug” model, the agency said.

The test’s effectiveness was established through “a least burdensome means” by comparing the F1CDx to previously FDA-approved companion diagnostic tests that are also used to match patients with treatments. The test accurately detected select mutation types (substitutions and short insertions and deletions) “representative of the entire 324 gene panel…approximately 94.6 percent of the time,” the FDA said.

Application of Tumor Profiling Questioned

The F1CDx is not the first next-generation sequencing–based in vitro diagnostic test cleared by the FDA for clinical use in oncology.

Just weeks ago, on November 15, the FDA authorized use of the Memorial Sloan Kettering (MSK) Cancer Center’s IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets) tumor profiling test, which can identify the presence of mutations in 468 unique genes.

Both are vitro diagnostic tests that use next-generation sequencing, and both also identify other molecular changes in the genomic makeup of a tumor. Both tests also have been touted as having utility in enrolling patients in clinical trials of targeted cancer therapies.

As previously reported by Medscape Medical News, a recent study of the  MSK-IMPACT test was published online September 5 in JAMA.

In a case series of 1040 patients with 18 different types of advanced cancers at MSK, 101 of the 182 (55.5%) patients with clinically actionable mutations would not have been detected through guideline-based, traditional genetic testing approaches, which translated to 9.7% of the entire cohort of 1040 patients, MSK researchers reported.

However, in an accompanying editorial, medical oncologist Eliezer M. Van Allen, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, questioned the clinical utility of these massive gene panels.

“From a practical implementation perspective, significant investments in the appropriate infrastructure, pretest counseling, reporting mechanisms, interpretation, and downstream clinical management are necessary” to study this testing in multiple contexts, including community settings, he wrote.

He gave an example from the study: Roughly two variants of uncertain significance were identified in each patient. “These ambiguous findings may result in higher rates of emotional stress, unnecessary testing, and overtreatment in an already encumbered advanced cancer population,” he commented.

“Precision oncology will need a fair amount of studies to determine the therapeutic utility of this approach,” Dr Van Ellen told Medscape Medical Newsat the time.

To read this entire article on MedScape.com, please click here.