Important New Target Identified for Ovarian Cancer Therapy

News-Medical.net

Scientists at Lawson Health Research Institute have uncovered an important new target for ovarian cancer therapy. Contrary to current research this new study found that LKB1, a molecule that regulates the metabolism of many adult cells, is an important molecule in the cancer’s promotion and survival.

Thousands of women are living with ovarian cancer in Canada. It is estimated that this year, 2,800 Canadian women will be newly diagnosed with this disease. Even though ovarian cancer continues to be one of the most serious women’s cancers, there is a real lack in reliable early detection tests and few treatment options. Lawson’s Dr. Trevor Shepherd is one of a few scientists across Canada solely dedicated to finding a cure for ovarian cancer.

By the time of diagnosis the majority of women with ovarian cancer already have extensive spread of the disease which makes it difficult to treat by surgery or chemotherapy. According to Dr. Shepherd, what is even more concerning is the propensity of the disease to keep coming back until it is eventually resistant to therapy.

In order to find out how and why ovarian cancer cells grow and take on such lethal characteristics, Dr. Shepherd and his team grow the cancer cells in 3D structures, called “spheroids” – the same way the cancer cells grow in patients. Spheroids are sticky and can attach themselves to different organs, such as the uterus, liver, stomach or small intestine. Here they can sit dormant and unnoticed for months or years before growing and becoming resistant to chemotherapy.

Recently, Dr. Shepherds’ lab discovered that the spheroids activate a ‘stress signal’, and the major molecule controlling this signal is called LKB1. “Previous studies stated that LKB1 was a tumour suppressor in ovarian cancer, meaning that tumour cells need to get rid of LKB1 to cause cancer,” says Dr. Shepherd “but our work is in direct conflict with these studies, because we definitively show that ovarian cancer cells still have LKB1 and that this molecule allows ovarian cancer spheroids to change their metabolism, promote tumour cell survival and make them more resistant to chemotherapy.”

By refuting these previous studies, Dr. Shepherd has uncovered a new target for future therapy. “There are currently no therapies or drugs that target LKB1,” states Dr. Shepherd. “Based on these findings our lab is exploring several different strategies to understand and target LKB1 and its related molecules in ovarian cancer spheroids, and developing the essential pre-clinical models to see if this can be translated to ovarian cancer patients.”

The study, “Intact LKB1 activity is required for survival of dormant cancer spheroids” is published in the June 5 online edition of Oncotarget.

Source:

Lawson Health Research Institute | http://www.news-medical.net/news/20150723/Important-new-target-identified-for-ovarian-cancer-therapy.aspx

Immunotherapy Granted Orphan Drug Status for Ovarian Cancer

CancerNetwork — Journal of Oncology |  By Cancer Network Staff

The US Food and Drug Administration (FDA) granted Orphan Drug Designation to an immunotherapy known as DPX-Survivac, which is in development for the treatment of ovarian cancer. The drug has produced some positive phase I results and is also being tested in recurrent diffuse large B-cell lymphoma.

P_Immunotherapy
“Receiving Orphan Drug Designation for ovarian cancer underlines the fact that DPX-Survivac may address a significant unmet medical need for this important disease,” said Marc Mansour, the CEO of the drug’s developer, Immunovaccine, in a press release. “Immunotherapy could change the way we treat all cancers in the future, and we plan to continue to study of DPX-Survivac for the treatment of ovarian cancer as well as other solid tumor types and blood cancers.”

The immunotherapy targets the tumor antigen survivin, which the company says is found in more than 90% of ovarian tumors. The orphan drug designation follows an earlier fast track designation for DPX-Survivac, specifically for patients with advanced ovarian, fallopian tube, or peritoneal cancer with no measurable disease following initial surgery and front-line therapy.

The FDA’s new move follows the publication of results from a small phase I trial in OncoImmunology in May of this year. DPX-Survivac was tested in combination with the immune-modulator metronomic cyclophosphamide in 19 patients with ovarian cancer. They found that the therapy induced survivin-specific immune responses in all patients, and that higher dose of the vaccine and cyclophosphamide generated responses of higher magnitude.

“The level of immune activation observed both quantitatively and qualitatively is unprecedented in a cancer population,” wrote study authors led by Neil L. Berinstein, MD, of Sunnybrook Health Sciences Centre in Toronto. “This vaccine combination may be an ideal candidate for further combination with other promising immunotherapeutics such as checkpoint inhibitors.”

Though the trial was not powered for observation of clinical activity, the authors noted that after 6 months, 12 of 18 patients remained without clinical progression. Further follow-up is ongoing.

According to ClinicalTrials.gov, DPX-Survivac is being tested in ovarian, fallopian, and peritoneal cancer, as well as in a phase II study of patients with recurrent diffuse large B-cell lymphoma. That trial also uses the immunotherapy in combination with cyclophosphamide.

– See more at: http://www.cancernetwork.com/ovarian-cancer/immunotherapy-granted-orphan-drug-status-ovarian-cancer#sthash.rwpE4F9q.dpuf

The Importance of Weight-based Chemo Guidelines for Women with Ovarian Cancer

By Lauren M. Green @OncNurseEditor

Elisa Bandera, MD, PhD
Elisa Bandera, MD, PhD

Women with ovarian cancer who experienced an average dose reduction of ≤85% had a 35% higher mortality risk than those who received normal dosing (85%-100%). The dose reductions were more likely to occur in overweight or obese patients, according to findings from a study published online in JAMA Oncology.

“Our study is the first to evaluate the impact of dose reduction on survival after an ovarian cancer diagnosis in normal weight, overweight, and obese women,” said lead study author Elisa Bandera, MD, PhD, epidemiologist at the Rutgers Cancer Institute of New Jersey, in a statement. “We found that for each body mass index category, ovarian cancer patients with dose reduction experienced a poorer survival rate.”

In a cohort study, investigators with the Rutgers Cancer Institute of New Jersey and the Kaiser Permanente Northern California (KPNC) Division of Research evaluated data from 806 women at KPNC receiving first-line treatment for their epithelial ovarian cancer with adjuvant carboplatin and paclitaxel. Data were obtained from electronic medical records and the KPNC Mortality Linkage System.

The median patient follow-up time was 52.5 months. Primary outcome measures included overall and ovarian cancer–related mortality.

Across the study, 30%, 31%, and 3% of patients, respectively, were categorized as obese (BMI ≥30), overweight (BMI = 25-29), and underweight (BMI <18.5). Compared with women of normal weight, obese women received less paclitaxel and carboplatin per kilogram of body weight and lower dose intensity.

Overall, lower dose intensity yielded worse outcomes—regardless of BMI—and was an independent predictor of ovarian cancer mortality. Researchers noted that the effect of dose reduction was actually strongest among normal-weight women, and this finding held true even after accounting for such diagnostic and prognostic factors as posttreatment CA-125 levels, disease stage, and comorbid conditions.

High BMI was the strongest predictor of dose reduction. Women who were obese class III (BMI ≥40) received 38% lower doses in mg/kg of paclitaxel and 45% lower doses of carboplatin, compared with normal-weight women. For these women, the mean average relative dose intensity (ARDI) was 73.7% compared with 88.2% for their normal-weight counterparts.

An ARDI of <70% was linked to worse overall survival (HR = 1.62; 95% CI, 1.10-2.37) and ovarian cancer–specific survival (HR = 1.69; 95% CI, 1.12-2.55). Although women who were obese at diagnosis appeared to have better survival rates, that advantage disappeared when their chemotherapy dose was reduced.

Chemotherapy dosing is generally based on a patient’s weight. However, dosing levels can vary considerably, in part because providers opt not to provide doses over a certain level due to worries over increased toxicity. For cancer patients who are overweight, this results in reducing the chemotherapy dose per pound of body weight—and possibly the effectiveness of chemotherapy in improving outcomes.

The study authors noted that much of the data on chemotherapy dosing—upon which the ASCO expert panel–derived guidelines are based—are drawn from breast cancer research, and less is known about chemotherapy dosing in patients with ovarian cancer who are overweight or obese. They hope that their cohort analysis will now offer some guidance in this area.

“Our observations suggest that body size should not be a principal reason for reducing chemotherapy dose in women with ovarian cancer,” noted senior author Lawrence H. Kushi, ScD, epidemiologist at the KPNC Division of Research, in a statement. The authors concluded that, “neither survival nor toxicity is worse when obese women are given full drug doses of chemotherapy.”

– See more at: http://www.onclive.com/web-exclusives/failure-to-follow-weight-based-chemo-guidelines-lowers-survival-in-ovarian-cancer#sthash.5JkeXK32.dpuf

The Scientist Becomes the Survivor and Advocate

The Scientist Becomes the Survivor and Advocate

Laura K. Shawver, PhD, is no stranger to biomedical research and cancer science in particular. She received her doctorate in pharmacology from the University of Iowa and did postdoctoral training at the University of Virginia Cancer Center and Washington University in St. Louis. Following her time in academia, Shawver decided to enter the pharmaceutical world, where she has made important contributions to the development of novel cancer therapeutics, including the receptor tyrosine kinase inhibitor sunitinib (Sutent), currently marketed by Pfizer to treat kidney and stomach cancer.

Dr. Laura Shawver.
Dr. Laura Shawver.

Shawver quickly earned a reputation as a leader in the pharmaceutical and biotechnology industries. Prior to her current position as chief executive officer of Cleave Biosciences, she served as president of SUGEN, Inc. and chief executive officer of Phenomix Corporation. But along that journey, she encountered a life-changing stumbling block: an ovarian cancer diagnosis.

“Being diagnosed with ovarian cancer changed the way that I think about cancer research and drug development,” recalls Shawver. “Being a cancer drug developer provided me the knowledge that I faced an uphill battle with my diagnosis, the feeling of desperation because I knew the odds were against me.” To face this challenge, she remembers, “I had to have the right team around me.”

After her diagnosis, she realized that this was an opportunity for her to forge a new approach to overcoming ovarian cancer. Indeed, her extensive experience as a cancer researcher and pharmaceutical leader, coupled with her now very personal experience with cancer, motivated Shawver to take this opportunity head on. In 2008, she launched The Clearity Foundation, a nonprofit organization focused on bringing molecular profiling to the forefront of ovarian cancer diagnosis and treatment to help women live longer, healthier lives.

“One of the reasons that I founded Clearity Foundation,” says Shawver, “was because I felt that we could be an important part of the team for other women – especially women whose cancer recurred following standard-of-care chemotherapy or when their treatment failed.”

Treatment failure is a common problem among ovarian cancer patients. Shawver states that “the approved drugs for recurrent ovarian cancer rarely work in more than 20 percent of patients.” That is a four in five chance that patients with recurrent ovarian cancer will receive toxicity without benefit, a startling statistic. “There are several drugs approved for recurrent ovarian cancer and multiple drugs in clinical trials,” she says, “but we need to find a way to prioritize these based on the potential for efficacy rather than pick out of the hat.”

This is one of the main tenets of Clearity’s mission, to move the field of personalized medicine forward for ovarian cancer patients by providing access to molecular profiling and diagnostic tests that can better inform their treatment plan. Shawver hopes that this will eliminate a major barrier to treatment. “Physicians often go through all the FDA-approved drugs and only then do they think about a clinical trial or using a drug off-label,” she says. “After failing four to five different drugs,” Shawver adds, “the tumors become so heterogeneous that the likelihood of a significant effect of a clinical trial agent or off-label drug is low. We need to shift the paradigm and think about clinical trials in first or second relapse as well as bring the insurance companies on board so that they will pay for off-label agents that are appropriate based on molecular alterations that provide a therapeutic rationale.”

Clearity has provided molecular profiling, or “tumor blueprints,” for hundreds of women since its inception. These blueprints are continually added to a database that could uncover correlations between specific tumor blueprints and treatment outcomes, with the goal of providing even more precise information that can be used to guide treatment decisions. “The challenge,” says Shawver, “is to convince more companies to conduct more clinical trials in ovarian cancer and in the subsets of patients that have the best chance to benefit. All women with recurrent ovarian cancer should sign up for a trial that makes sense for them based on their tumor profile.”

Regarding the issue of clinical trials for ovarian cancer, Shawver advocates for a shift in approach. “The traditional approach of having several sites participate in the trial will take too long to enroll because there are so few of us, so we need to figure out how to bring the trial to the patient rather than the patient to the trial,” she says. “This is true for any rare cancer like ovarian cancer that has significant histological and molecular heterogeneity.”

In addition to her work with the Clearity Foundation, Shawver remains a leader in the biotechnology industry. At Cleave Biosciences, she continues to pave the way for the development of novel, effective cancer therapeutics, but with a new perspective. “For me, my cancer diagnosis led me to think differently about how to attack cancer from a non-oncogene addiction standpoint since many ovarian tumors do not have an oncogenic driver mutation,” she says. This is what led her to Cleave, whose focus is on targeting protein homeostasis and understanding pathway addiction. “We now have a drug that targets p97 (an enzyme responsible for destroying misfolded proteins in the cell) in two phase I clinical trials, one in solid tumors,” says Shawver. “It will come as no surprise that we spent considerable time and effort preclinically to understand the molecular determinants of sensitivity and resistance. This is an important part of our clinical strategy.”

When contemplating the future of ovarian cancer diagnosis and treatment, Shawver exudes an air of both determination and optimism. “While we have a number of uphill battles in the quest for a better treatment paradigm, one of our messages to women battling ovarian cancer is that tremendous progress is made every year and that by staying ‘in the fight’ even for six months, new treatment options may become available.”

“A recent example of this,” Shawver recalls, “was a woman with a BRCA-mutated tumor who was being treated for a second recurrence last year but she was not eligible for any of the clinical trials with the PARP inhibitors (drugs that prevent the repair of DNA damage and lead to tumor cell death). She had a third recurrence in January 2015 but because BRCA-targeting agent olaparib(Lynparza) was approved in December 2014, she was able to now have the ‘matched’ treatment. While PARP inhibitors do not work for everyone, she is back in remission with a good quality of life.”

Shawver hopes to be able to share more stories like this, and believes that improvements in outcome can be made, but she stresses that increased research and clinical trials are needed. “I have been a proud AACR member since 1992 so I have watched at conferences over the years the progress of many drugs that have had tremendous benefit for cancer patients. Unfortunately, this has been limited in ovarian cancer,” she says. However, as a member of the Stand Up To Cancer Scientific Advisory Committee, as well as the Joint Scientific Advisory Committee that selected the new SU2C-Ovarian Cancer Research Fund-Ovarian Cancer National Alliance-National Ovarian Cancer Coalition Dream Team, Shawver sees promising new opportunities for progress.

“I was so thrilled to participate in the selection of the Stand Up To Cancer Ovarian Cancer Dream Team and I know this will direct the field to an understanding of PARP inhibitors for a broader range of women as well as to understand how to combine the PARP inhibitors for more effective treatment,” she says.

Treatment Choices and Clinical Trials

The Clearity Foundation by Cory Bentley, PhD

A study presented at the Society of Gynecological Oncology meeting found that most women diagnosed with ovarian cancer are not receiving medical care that meets the guidelines of the National Comprehensive Cancer Network (NCCN). The study was presented in April by Dr. Robert Bristow of the University of California, Irvine and reviewed the medical records of more than 13,000 women with ovarian cancer. Surprisingly, the study found that only 37 percent of women were receiving the recommended standard of care. Importantly, the advanced stage patients who received the standard of care recommended by the NCCN guidelines lived longer than those who did not. Women treated by physicians with less experience treating ovarian cancer (those treating fewer than 10 cases per year) and women treated at “low-volume” hospitals (those treating fewer than 20 patients with ovarian cancer each year) were less likely to receive the standard of care. Faced with such a challenging environment, it is no wonder that many patients can be overwhelstock-footage-doctor-talking-with-her-patientmed and even skeptical.

At Clearity, we believe that one way to inform treatment selection is to use the results of tumor molecular profiling to help prioritize drugs among those recommended in the NCCN guidelines for recurrent ovarian cancer. Tumor profile reports can also be used to help select a drug or drug combination from among those that are currently in clinical trials.   When it comes to clinical trials, patients can have many reservations.

Dr. Teresa Gallagher has studied how patients consider clinical trial options. She explains that there are several important barriers that may deter women from deciding to participate in a clinical trial: Concern about being used as a “human guinea pig” to test potentially unsafe drugs; Mistrust of the drug companies and their motives; Fear of being assigned to a group where you will not receive the experimental treatment; Belief that you will not benefit from the trial drug — that currently available treatments are more effective than “experimental” treatments; Lack of awareness of appropriate trials that fit your molecular profile and other circumstances such as no available trials nearby and eligibility criteria. With all these questions and concerns, why would a patient consider a clinical trial? This question was put to Clearity’s scientific director, Deb Zajchowski, PhD.

According to Dr. Zajchowski, one compelling reason for participation in a clinical trial is the possibility of receiving a drug that could be a very effective treatment. “Many of the drugs that are now in clinical trials are predicted to work only in certain patients who can be identified by tumor molecular profiling approaches similar to those used by Clearity. It is hoped that by such selection, these new drugs will work in more patients than in the past when there was no selection process.” To those patients whose top concern is whether or not they receive the trial drug, Dr Zajchowski points out that randomized clinical trials compare a standard treatment with the same treatment with a new study drug added on top. Therefore, the patient who is in the placebo arm will still receive the standard treatment that is appropriate for her cancer. The clinical trial drug is in addition to the standard of care. A clinical trial makes a lot of sense for a patient when her molecular profile has matched her to the standard of care drug used in the trial as well as the new drug being tested. Another factor keeping women from participating in clinical trials is a concern about safety.

Safety issues are most pertinent for a phase I study, which is designed to evaluate the safety of a drug being used in human beings for the first time. Several aspects of a phase I study design help keep patients safe. First, substantial data is available on the safety of the drug in animal models; seconurld, patients are very closely monitored; third, the study starts with a very low dose and only increases to a higher dose after the lower dose proves tolerable; and lastly, a patient can withdraw from a trial at any time.

There is always a risk of experiencing side effects with a clinical trial drug, but Dr. Zajchowski explains, “The decision is a personal one where every patient must balance the risks with the possible benefits– the chance of receiving a new drug that could work better than any other drug to treat your cancer and the risk for a severe adverse reaction.” Both drug effectiveness and safety are critical to the success of any drug. Suspicion of drug companies’ motivations dissuades some patients from participating in clinical trials. Dr. Teresa Gallagher explains that unfortunately the pharmaceutical industry is being portrayed negatively in the media, which can cause patients to mistrust the drug companies and drug trials.

Cory Bentley, PhD, the author of this article, currently works in drug discovery and development for a biotechnology company, where real people are interested in making a real difference. In Dr. Bentley’s experience, people in drug companies and physicians running clinical trials are working to make a drug that will truly give something valuable to patients: extended life and quality of life. As patients look at clinical trials, there are so many issues to consider. Perhaps the most critical considerations are how well a trial drug matches her tumor molecular profile and practical concerns such as eligibility and distance from home. Clearity will help patients find their way to a treatment that best fits their molecular profile, whether that includes a trial drug or approved drug.

The information included in this newsletter is for educational purposes only. It is not intended nor implied that this information be a substitute for professional medical advice. You should always consult your healthcare provider to determine the appropriateness of the information for your own situation.

Eligibility Criteria in Clinical Trials: PARP Inhibitors

Eligibility Criteria in Clinical Trials: PARP Inhibitors

The Clearity Foundation

Dr. Cory Bentley, PhD

Clearity first reported on drugs inhibiting PARP (Poly-ADP ribose polymerase), an important enzyme for tumor cell proliferation and survival, in its September 2010 patient newsletter.  At that time, PARP inhibitors were just entering clinical trials and only two trials were recruiting patients. Now, thanks to promising results from the early

trials, multiple PARP inhibitors are moving forward in ovarian cancer clinical trials and are also being evaluated in other cancer types. PARP inhibitors have proven most effective in patients with a mutation in one of the BRCA genes (click here for a BRCA overview), but tumors with mutations in other DNA repair pathways may also be sensitive to PARP inhibition. A quick search of Clearity’s clinical trial search engine for ovarian cancer trials using “PARP1/2” as the search term in the targeted drug field pulls up 20 clinical trials.  Most are phase I studies but there will soon be new phase II and even phase III trials added.

In fact, four companies have indicated that they are moving PARP inhibitors into pivotal phase III trials for ovarian cancer soon, including Abbott, AstraZeneca, Clovis, and Tesaro.  All of these trials will evaluate the efficacy of these inhibitors as a maintenance therapy. As described in the accompanying article, maintenance therapy is given to patients that have responded to their previous treatment with the aim of prolonging their time to recurrence or progression.  For Abbott’s veliparib, the phase III study will be in newly diagnosed patients with stage 1C-IV high grade serous cancer in combination with platinum/paclitaxel with randomization to the maintenance therapy with either veliparib or placebo.  For the other three PARP inhibitor trials, the maintenance therapy is for women whose cancer recurred and responded again to platinum-based treatment.

Tesaro’s President, Mary Lynn Hedley, PhD talked with Clearity about the phase III trial for niraparib. The niraparib trial will have many study sites across North America. Patients will be randomized into the study drug group or placebo group 2:1, meaning that for every three patients that enroll, two will get the study drug and one will get the placebo.  Dr. Hedley explains that this 2:1 design study will take longer to complete because more patients are necessary for the trial, but she knows that it is important to patients that they have a good chance to be on the study drug. The niraparib trial will take patients regardless of their BRCA mutation status because some studies indicate that patients with high grade serous ovarian cancer can have mutations other than BRCA in DNA repair pathways that make them equally susceptible to PARP inhibitors.

AstraZeneca’s PARP inhibitor, olaparib, will be tested in phase III studies this year, but will specifically focus on patients who have BRCA mutations, based on good responses in those patients in their phase II studies.  According to the updated analysis for their phase II maintenance therapy study presented at the annual meeting of the American Society of Clinical Oncology (ASCO) on June 2, women with BRCA mutations (germline or tumor) had a significantly improved time to tumor progression: 11.3 months on olaparib vs. 4.3 months on placebo.

Clovis is also planning to start a phase III trial this year with its PARP inhibitor, rucaparib, for platinum-sensitive high grade serous ovarian cancer.  This trial will have a similar design to the one described for niraparib, but will additionally stratify patients based on BRCA status as well as evidence for other biomarkers associated with DNA repair defects.

It is clear that all of these phase III trials are paying close attention to patients’ tumor blueprint either to decide on enrollment or to help further identify which patients are most likely to respond to the respective drugs.

Apart from a patient’s tumor molecular profile or blueprint, many other factors determine patient eligibility, including the number and types of prior chemotherapies and other treatments, stage of disease, and health factors. For this reason, it is imperative that patients consider clinical trials early in their treatment, so that they do not inadvertently make themselves ineligible for participation in promising trials. Patients and their doctors have to be one step ahead of their cancers as they map out possible treatment paths.  Clearity can help by using each patient’s own blueprint to identify possible options that include both approved treatments and clinical trials. A number of Clearity’s patients have participated in PARP inhibitor trials.  Read about the experience of one of these women here.

The current and upcoming PARP inhibitor trials hold the promise of new treatment options for ovarian cancer patients. These studies will also bring a wealth of new data that will help guide future patients and their doctors to make informed treatment choices.

The information included in this newsletter is for educational purposes only. It is not intended nor implied that this information be a substitute for professional medical advice. You should always consult your healthcare provider to determine the appropriateness of the information for your own situation.

CA125 becomes a Target for Destruction of Ovarian Cancer by Phase I Drug

CA125 becomes a Target for Destruction of Ovarian Cancer by Phase I Drug

The Clearity Foundation

Dr. Cory Bentley, PhD

Most ovarian cancer patients have become familiar with CA125 blood level monitoring, but trial drug DMUC5754A from Genentech puts a new twist on this familiar blood marker of advanced ovarian cancer. CA125 (cancer antigen 125) also goes by the name mucin 16, Muc16 for short. Muc16 is overexpressed on the cell surface of most ovarian cancers compared to normal tissue. So while Muc16 in the blood may be a biomarker for ovarian cancer, on the tumor cell surface it targets the cell for destruction by DMUC5754A.
DMUC1DMUC5754A is a so-called therapeutic antibody that specifically binds to Muc16. It is much like the antibodies that one’s body naturally makes to fight off infection and invaders. DMUC5754A is also an armed antibody by its linkage to a highly toxic drug, MMAE (monomethyl auristatin E). An armed antibody is known as an ADC – antibody drug conjugate.
Phase I clinical trial data for ADC DMUC5754A were presented at this year’s American Association for Cancer Research (AACR) Annual Meeting in April. This phase I study evaluated several aspects of this drug in advanced recurrent platinum-resistant ovarian cancer, including safety and activity. This phase 1 trial had two parts; first, dose escalation to determine the maximum tolerated dose (MTD) and then expansion for further analysis at the MTD. Dose escalation design starts patients on a very low dose of the drug. These patients are closely monitored for side effects. If side effects are mild, the next group of patients receives a higher dose of the drug. Dose escalation continues in successive groups of patients until strong side effects are observed in greater than 30% of patients, establishing the MTD for DMUC5754A. The expansion part of the trial involved 22 more patients at this highest dose to test for potential efficacy and confirm the safety.
Of the 29 patients treated at the MTD, one complete response was observed (no evidence of cancer after treatment) and 4 partial responses were observed (decreased tumor size). All responses were seen in patients whose tumors expressed moderate to high levels of the targeted protein Muc16, suggesting that using Muc-16 expression on tumor cells will help to identify responsive patients in the future. Dr. Joyce Liu, who presented the phase I study, concluded that DMUC5754A “has an encouraging safety profile and evidence of anti-tumor activity in MUC16-expressing ovarian cancer.”
Finding responders in this group of patients is not a small feat. Patients in this study were heavily pre-treated, averaging 4 prior therapies, and platinum-resistant. This study exemplifies why clinical trials bring true hope to ovarian cancer patients. Although DMUC5754A must still prove its value in phase II and III trials, results from this phase I trial are hopeful.
The information included in this newsletter is for educational purposes only. It is not intended nor implied that this information be a substitute for professional medical advice. You should always consult your healthcare provider to determine the appropriateness of the information for your own situation.