2011 ASCO: EntreMed’s ENMD-2076 Demonstrates Clinical Activity in Recurrent, Platinum-Resistant Ovarian Cancer Patients

EntreMed, Inc. announced that ENMD-2076 demonstrated clinical activity — a six-month progression free survival rate of 19% — when administered as a single agent to platinum drug-resistant recurrent ovarian cancer patients. The announcement is based upon interim phase 2 data presented today at the 2011 American Society of Clinical Oncology Annual Meeting. 

Ursula A. Matulonis, M.D., Medical Director, Gynecologic Oncology, Dana-Farber Cancer Institute; Associate Professor of Medicine, Harvard Medical School

EntreMed, Inc., a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer announced today the presentation of clinical data for its phase 2 study with ENMD-2076 in platinum drug-resistant recurrent ovarian cancer patients. The data were presented by the principal investigator for the study, Dr. Ursula A. Matulonis, medical director of gynecologic oncology at the Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, during a poster discussion session at the American Society of Clinical Oncology (ASCO) Annual Meeting being held June 3 – 7, 2011 in Chicago, Illinois.

The trial was an open-label, single-arm, multicenter study of ENMD-2076 dosed orally as a single agent in patients with platinum-resistant recurrent ovarian, peritoneal or fallopian tubal cancer. The study was conducted at six sites in the United States and Canada and included the Dana-Farber Cancer Institute, Indiana University Melvin & Bren Simon Cancer Center, University of Chicago Medical Center, Memorial Sloan-Kettering Cancer Center, University of Colorado Cancer Center, and Princess Margaret Hospital. Sixty-four patients were enrolled, of which 57 were evaluable at the time of the presentation. The primary endpoint for the study was progression-free survival rate at six months. Secondary end-points include response rate, duration of response, and overall survival.

ENMD-2076 demonstrated clinical activity when administered daily orally as a single agent. Interim data from 57 evaluable patients showed a six-month progression free survival rate of 19 percent. Of the evaluable patients, four patients achieved a partial response and 30 patients achieved stable disease as measured by RECIST v1.1. Median overall survival has not yet been reached. The side effect profile was consistent with activity against ENMD-2076’s molecular targets, in particular, VEGFR2 (vascular endothelial growth factor receptor-2) and Aurora A. Studies to evaluate potential markers of ENMD-2076 in this patient group are ongoing.

Dr. Matulonis commented on the results of the study, “ENMD-2076 has demonstrated impressive anti-cancer activity in platinum-resistant ovarian cancer which is notoriously difficult to treat, and these patients have few options.”

EntreMed’s chief medical officer, Carolyn F. Sidor, M.D., M.B.A., added, “These results are very encouraging as they support further development of ENMD-2076 and also help us clarify its developmental path in ovarian cancer. We are currently designing the next clinical trial in this indication and look forward to opportunities to make ENMD-2076 available to ovarian cancer patients in the future.”

About ENMD-2076

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases which have been shown to play important roles in the pathology of several cancers. ENMD-2076 has shown promising activity in phase I clinical trials in solid tumor cancers, leukemia, and multiple myeloma. While ENMD-2076 is currently in a phase 2 trial in ovarian cancer, preclinical and clinical activities are ongoing in assessing the compound’s applicability in other forms of cancer.

To view an Adobe Reader PDF copy of the presentation, visit http://www.entremed.com/files/umatulonis_enmd_2076_p2_ovarian.pdf

About EntreMed

EntreMed, Inc. is a clinical-stage pharmaceutical company committed to developing ENMD-2076, a selective angiogenic kinase inhibitor, for the treatment of cancer. ENMD-2076 is currently in a multi-center phase 2 study in ovarian cancer and in several phase 1 studies in solid tumors, multiple myeloma, and leukemia.

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Dana-Farber Researchers “OncoMap” The Way To Personalized Treatment For Ovarian Cancer

Researchers have shown that point mutations – mis-spellings in a single letter of genetic code – that drive the onset and growth of cancer cells can be detected successfully in advanced ovarian cancer using a technique called OncoMap. The finding opens the way for personalized medicine in which every patient could have their tumor screened, specific mutations identified, and the appropriate drug chosen to target the mutation and halt the growth of their cancer.

Researchers have shown that point mutations – mis-spellings in a single letter of genetic code – that drive the onset and growth of cancer cells can be detected successfully in advanced ovarian cancer using a technique called OncoMap. The finding opens the way for personalized medicine in which every patient could have their tumor screened, specific mutations identified, and the appropriate drug chosen to target the mutation and halt the growth of their cancer.

Using mass spectrometry for identifying the genetic make-up of cancer cells, OncoMap can determine the point mutations in tumors by utilizing a large panel of over 100 known cancer-causing genes (referred to as “oncogenes“). In the work to be presented today (Wednesday) at the 22nd EORTCNCIAACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Berlin, researchers will describe how they used OncoMap to identify oncogene mutations in tumor samples obtained from women with advanced high-grade serous ovarian cancer. [2] Earlier in the year 76 mutations in 26 different genes had been found but, since then, further work in more tumor samples has found more.

Ursula A. Matulonis, M.D., Medical Director, Gynecologic Oncology, Dana-Farber Cancer Institute; Associate Professor, Medicine, Harvard Medical School

Dr. Ursula Matulonis, director/program leader in medical gynecologic oncology at the Dana-Farber Cancer Institute located in Boston, Massachusetts (USA) and Associate Professor of Medicine at Harvard Medical School, will tell the meeting:

“Epithelial ovarian cancer is the most lethal of all the gynecologic malignancies, and new treatments are needed for both newly diagnosed patients as well as patients with recurrent cancer. The success of conventional chemotherapy has reached a plateau, and new means of characterizing ovarian cancer so that treatment can be personalized are needed.

We know that many human cancers have point mutations in certain oncogenes, and that these mutations can cause cancer cells to have a dependence on just one overactive gene or signalling pathway for the cancer cell’s growth and survival – a phenomenon known as ‘oncogene addiction’. If the mutation that causes the oncogene addiction can be inhibited, then it seems that this often halts the cancer process. Examples of mutations that are successfully inhibited by targeted drugs are HER2 (for which trastuzumab [Herceptin®] is used in breast cancer), EGFR (erlotinib [Tarceva®] in lung cancer) and c-kit (imatinib [Gleevec®] in chronic myeloid leukemia). So if we know the status of specific genes in a tumor, then this enables us to choose specific treatments that are likely to work successfully against the cancer.”

Dr Matulonis and her colleagues used OncoMap to investigate the mutation status of high-grade serous ovarian tumors that were known not to be caused by inherited mutations in the BRCA 1 and BRCA 2 genes. They found mutations previously identified to be involved in ovarian cancer: KRAS, BRAF, CTNNB1 and PIK3CA. The KRAS and PIK3CA mutations were the most common, while BRAF was more rare. The researchers also identified a low frequency of mutations in many other different oncogenes.

Dr. Matulonis further noted:

“This study shows that it’s feasible to use OncoMap to identify whether a patient’s tumor has a mutation in an oncogene for which a known drug is available to target that specific gene, so as to enable us to place her on a clinical study of that drug; for instance, XL147 or GDC-0941 are inhibitors for the P13kinase mutation that are in clinical trials at present.  In addition, someone’s cancer could harbor a mutation (such as ALK) that is not known to be associated with ovarian cancer or has not yet been studied in ovarian cancer – these patients could be matched with a drug that inhibits that protein too. As new drugs get developed, this information would be used to match future drugs with patients and their cancers.”

The researchers hope that OncoMap will become a clinical test for all cancer patients at the Dana-Farber Cancer Institute before long, so that the genetic information obtained can be used to choose the best treatment for them.

Dr. Matulonis said:

“At present, only a few targeted therapies are being used for newly diagnosed ovarian cancer and most are being used to treat recurrent ovarian cancer, but this will change eventually. I have already referred several of our patients who are either newly diagnosed or have recurrent cancer and who have mutations (one with KRAS and one with PIK3CA) to our phase I program for drugs studies specific to these mutations.  For ovarian cancer, understanding mutational analysis is one piece of the genetic puzzle. Our group will also start looking for chromosomal and gene amplifications and deletions in patients’ tumors, which we know are important for ovarian cancer.”

Matulonis believes that OncoMap and other similar analytical tools will become mainstream practice in all cancer clinics before long. Tools for detecting genes with the incorrect numbers of copies or abnormal expression will also help doctors to choose the best treatment for individual patients.”

Source: Researchers map the way to personalised treatment for ovarian cancer, Abstract no: 35. Oral presentation in plenary session 2.  22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Berlin, Germany, November 16- 19, 2010.

References:

[1] EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].

[2] The study was funded by the Madeline Franchi Ovarian Cancer Research Fund, twoAM Fund and the Sally Cooke Ovarian Cancer Research Fund.

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Patty Franchi Flaherty Loses Battle to Ovarian Cancer, But Deserves a Long Standing Ovation

It is with deep regret that I must inform you that, Patty Franchi Flaherty, founder of the nonprofit organization Ovations for the Cure of Ovarian Cancer, peacefully succumbed to her nine-year battle with the disease on August 18, 2008, surrounded by friends and family. She was 53 years old. Patty was a legendary ovarian cancer advocate, who spoke for ovarian cancer survivors that lacked a voice. Inspired by the death of her mother from ovarian cancer nearly 35 years ago and driven by her personal struggle, she founded the Natick-based nonprofit Ovations for the Cure in 2005. The organization has since comforted countless women and donated over $1 million to various ovarian cancer research programs at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, including the world-renowned Desensitization Program, through fundraising programs such as the annual Stuart Weitzman Fashion Show.

It is with deep regret that I must inform you that, Patty Franchi Flaherty, founder of the nonprofit organization Ovations for the Cure of Ovarian Cancer (Ovations For the Cure), peacefully succumbed to her nine-year battle with the disease on August 18, 2008, surrounded by friends and family. She was 53 years old. Patty was a legendary ovarian cancer advocate, who spoke for ovarian cancer survivors that lacked a voice.

Inspired by the death of her mother from ovarian cancer nearly 35 years ago and driven by her personal struggle, she founded the Natick-based nonprofit Ovations for the Cure in 2005. The organization has since comforted countless women and donated over $1 million to various ovarian cancer research programs at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, including the world-renowned Desensitization Program, through fundraising programs such as the annual Stuart Weitzman Fashion Show.

We provide below a bylined article about Patty Franchi Flaherty that was graciously provided to us by Ovations For the Cure. If you would like to learn more about the warnings signs and symptoms of ovarian cancer, CLICK HERE (Ovarian Cancer Symptoms Consensus Statement (Adobe Reader PDF Document)

“Patty Franchi Flaherty loses battle to ovarian cancer

Patty Franchi Flaherty, Founder of Ovations For the Cure of Ovarian Cancer (February 26, 1955 – August 18, 2008)

Patty Franchi Flaherty, Founder of Ovations For the Cure of Ovarian Cancer (February 26, 1955 – August 18, 2008)

Natick, MA (August 19, 2008) – Patty Franchi Flaherty, Founder and President of Ovations for the Cure, lost her courageous 9-year battle with ovarian cancer and died peacefully at home on August 18, 2008, surrounded by family and friends.

Patty was a native of Weston who graduated from Bentley College in Waltham. Afterward, she joined Natick-based Franchi Management Company, Inc., where she worked as General Manager for over 30 years overseeing all business operations. She was also a long-standing trustee at Boston’s Dana-Farber Cancer Institute.

Diagnosed with ovarian cancer in early 1999, Patty lived 9 years before succumbing to the same disease that took her mother Madeline’s life 25 years earlier. After a promising remission, the cancer resurfaced in 2005. Frustrated by how little ovarian cancer diagnosis and treatment had changed in a quarter-century, Patty was certain that she wasn’t alone in her fight with ovarian cancer or in her frustration over medical insufficiencies. She was determined to help improve the odds for all ovarian cancer patients.

In early 2006, Patty co-hosted the Stuart Weitzman Fashion Show and Luncheon as a fundraiser. Proceeds from the show helped fund the Madeline Franchi Ovarian Cancer Research Fund at the Dana-Farber Cancer Institute. Then, with the help and support of her dearest friends, Patty launched a non-profit organization called Ovations for the Cure to fuel other research initiatives around the country and actively change the face of ovarian cancer.

In the 9 years she lived with ovarian cancer, Patty Franchi Flaherty turned a very personal crusade into a meaningful legacy for all women facing the disease. Thanks to Patty, women can now share information the likes of which her mother never had, and have hope where before there had been none. In just over 3 years’ time, Patty led Ovations’ growth from a lingering idea to a thriving organization-with momentum that continues to build across North America.

In July of 2008, The Savings Bank Life Insurance Company of Massachusetts awarded Patty its highest community honor, the prestigious Brandeis Award, which Patty’s husband Paul accepted on her behalf. The award pays homage to [U.S. Supreme Court] Justice Louis Brandeis and his defense of the rights of individuals, and was given to Patty in recognition of her innovation, bravery, and commitment to furthering the research and awareness of ovarian cancer.

Known for her unshakable determination, Patty turned her mission to beat ovarian cancer into a nationwide entity. In so doing, she created a living legacy of hope for everyone who faces the disease. Patty’s personal contributions to the fight against ovarian cancer have earned her a champion’s status in the hearts of those she has forever touched.

Creating a brighter future

Compared with other diseases making headlines today, ovarian cancer is far from attention-grabbing. Its foremost symptoms are so common and nonspecific that they are often mistaken for something else, if not ignored. Meanwhile, early detection methods are still in their infancy and late-stage diagnosis makes for only a limited number of successfully treated patients. Perhaps most surprisingly, ovarian cancer has the highest mortality rate of all gynecologic cancers.

Contributing to the high mortality rates of ovarian cancer is the lack of accurate screening and clear symptoms. As a result, only 19 percent of cases are detected before the cancer has spread beyond the ovaries, when treatment options are limited.

‘Ovarian cancer is often misunderstood, misinterpreted, and unfortunately misdiagnosed,’ said Dr. Ursula Matulonis, attending physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and medical advisor to Ovations for the Cure.

‘In an effort to overcome this silent killer, Ovations for the Cure is dedicated to supporting cancer research centers to find accurate and early detection screenings. If caught in the early stages of diagnosis, ovarian cancer patients have a 90 percent chance of survival beyond five years and increased odds of beating the disease,’ Matulonis added. ‘Ovations for the Cure has helped change the dynamics of the medical profession by contributing valuable research funds for detection and treatment while educating women on its subtle symptoms.’

Today, Ovations continues to help make miracles possible for all women with ovarian cancer by shedding light on a disease that is still full of darkness. They have launched an aggressive ovarian cancer educational program, distributing awareness brochures to more than 3,000 physicians’ offices across the nation. Additionally, the development of their television and radio public service announcements outlining ovarian cancer symptoms has helped women identify the disease before it spreads to advanced stages. By spring of 2008, Ovations had already dedicated nearly one million dollars to ovarian cancer initiatives through the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, City of Hope Hospital in L.A., and the University of Pennsylvania.

From loss to legacy

‘Patty started Ovations for the Cure with the idea of saving women from this horrible disease,’ said Debbie Soprano, one of Patty’s closest friends and first Executive Director of Ovations for the Cure. ‘While she could not save herself, her everlasting optimism and spirit will forever lead the fight against ovarian cancer until we find a cure.’

Patty Franchi Flaherty may have lost her own battle against ovarian cancer, yet through Ovations for the Cure, she’ll continue to help thousands of women to win the war. For more information about ovarian cancer visit www.ovationsforthecure.org”

About Ovations for the Cure

The Ovations for the Cure Foundation, a 501(c)(3) non-profit organization, is dedicated to the relentless pursuit of a cure for ovarian cancer. Ovations for the Cure has donated over $1 million to various ovarian cancer research initiatives such as the Dana-Farber Cancer Institute, Children’s Hospital Boston, City of Hope, University of Pennsylvania, and Brigham and Women’s Hospital. The Foundation spreads awareness of the most deadly gynecological disease through national events including the renowned Happy Feet Program, fashion shows with celebrity designers Stuart Weitzman and Carmen Marc Valvo, regional golf outings, 5k runs/walks, and various other initiatives. For more information about Ovations, please visit www.ovationsforthecure.org.