INNOVATE-3 Trial Examining Tumor Treating Fields in Platinum-Resistant Ovarian Cancer Recommended to Continue

This is a shortened version of an article written by Kristi Rosa and published in OncLive March 24, 2022

An independent data monitoring committee (DMC) has recommended that the phase 3 INNOVATE-3 trial  exploring the safety and efficacy of tumor treating fields (TTFields) in combination with paclitaxel in patients with platinum-resistant ovarian cancer proceed to the final analysis, according to an announcement from Novocure.

The recommendation follows a review of safety findings for all the patients enrolled to the trial, and an analysis of overall survival (OS) that was done on the first 540 patients who underwent randomization. Data from the prespecified interim analysis of the trial did not signal for a need to increase the sample size, and so the trial will continue as planned.

“Completion of the DMC interim analysis represents the next milestone in our journey to address the significant unmet need for patients diagnosed with platinum-resistant ovarian cancer,” Ely Benaim, MD, chief medical officer of Novocure, stated in a press release. “I would like to thank our investigators and collaborators, ENGOT and The GOG Foundation, as well as our patients for their passion and bravery. We look forward to reviewing final data next year.”

TTFields are electric fields that disturb cancer cell division. These fields can hinder electrically charged cellular components of cancer cells and disrupt their function, which could result in cell death. With this approach, cancer cell division can either be slowed down or stopped. Utilizing the investigational medical device referred to as NovoTTF-200(O), the fields are delivered to the region of the body where the tumor is located. [Learn more about TTFields here]

The pivotal, open-label, phase 3 INNOVATE trial enrolled patients with a histologically confirmed diagnosis of ovarian carcinoma that has been unresponsive to therapy containing platinum within 6 months of their last treatment, who are at least 18 years of age and have a life expectancy of at least 12 weeks. Patients needed to be amenable to receive weekly paclitaxel and be able to operate the NovoTTF-200(O) device.

Study participants were randomized to receive either weekly paclitaxel alone or weekly paclitaxel concomitantly with TTFields tuned to 200 kHz until disease progression.

The primary end point of the trial is OS [overall survival], and key secondary end points include progression-free survival (PFS), objective response rate, severity and frequency of adverse effects, time to deterioration in health-related quality of life (QOL) or death, and QOL.

As of October 2021, the study has accrued a total of 540 patients. Data from the trial are anticipated to be reviewed in 2023, after an 18-month follow-up period.

Previously, TTFields in combination with weekly paclitaxel was observed in patients with platinum-resistant ovarian cancer as part of the single-arm, phase 2 INNOVATE trial (NCT02244502).

Ovations for the Cure of Ovarian Cancer Fundraising Event

 Let's Support Our Sister Organization:

JOIN US AT PUTTS & MORE FOR FUN AND FUNDRAISING!

 

MAY 21, 2022 1OAM TO 2PM

750 Concord Street, Holliston, MA

 

18 HOLE MINI GOLF

  $15 PER PERSON (AGES 9 and up)

$10 PER PERSON (AGES 3 -8)

 

NO PRESALES - PAY AT THE GOLF COURSE!

 

PLAY GOLF, VISIT WITH FRIENDS, ENJOY A SNACK FROM THE SNACK BAR AND HELP SUPPORT OUR PATIENT PROGRAMS.

 

Picnic table area also available

 

For more info on Putts and More, please visit

https://puttsandmore.com/

For more information contact:  susan@ovationsforthecure.org 

 

 Ashton Thompson becomes the first National Ovarian Cancer Coalition (NOCC) Athletic Ambassador, committed to spreading awareness on and off the track

From the National Ovarian Cancer Coalition, story copied from EINPresswire:

DALLAS, TX, UNITED STATES, March 8, 2022 /EINPresswire.com/ -- 1 in 78 - no, that’s not the ratio of female to male drivers in the racing world, that is a woman’s risk of getting ovarian cancer in her lifetime. Kenyon Midget race fans will spend the 2022 season learning about the risks, signs, and symptoms of ovarian cancer thanks to the NOCC’s first Athletic Ambassador, Ashton Thompson. “After looking into the NOCC, I quickly realized that this partnership would be a huge success. I want to do everything I can to spread awareness for ovarian cancer and be here to support anyone who has to endure this horrible disease.”

As an Athletic Ambassador for the organization, Thompson will support early awareness and education initiatives in a sport with plenty of female fans, but few female drivers to look up to. As the only female driver in the field this race season, Thompson’s unique perspective and passion for racing will inspire women across the country to take action and advocate for their health. "We are proud to have Ashton join us in bringing much-needed awareness to ovarian cancer,” shared NOCC CEO Melissa Aucoin, “ a disease that impacts over 21,000 women in the U.S each year, and so grateful to have her heroic commitment in reaching and empowering new audiences of women everywhere with lifesaving health messages."

NOCC and Ashton Thompson Racing are excited to partner during the 2022 race season to break barriers on the track and break the silence on ovarian cancer. To learn more about the 2022 Kenyon Midget Race Season and where you can catch Ashton, visit ashtonthompsonracing.org.

Study in Finland Reveals How Ovarian Cancer Cells Hide from the Immune System

This article is taken from ScienceDaily

Every year, roughly 550 women develop ovarian cancer in Finland. Ovarian cancer is difficult to treat and it is commonly fatal, with 320 women dying of ovarian cancer annually in Finland.

Cancer can only develop and progress when the tumor cells are able to hide from the body's immune system. Cancer immunotherapies, which boost the body's immune defense against cancer, have emerged as promising therapies in multiple tumor types. However, the effectiveness of immunotherapies against ovarian cancer has remained modest. This is mainly since the mechanisms how ovarian cancer cells hide from the immune system have been unknown.

Now, researchers at the University of Helsinki have uncovered how tumor cells interact with the immune system in ovarian cancer. Utilizing a novel imaging technology, the researchers characterized more than 110,000 individual cells from clinical ovarian cancer samples. The researchers investigated how the genetic characteristics of ovarian cancer the shape human immune system, and how tumor and immune cells communicate with each other.

"With the help of this revolutionary imaging technology and advanced data analysis, we were able to study individual tumor cells, their functional properties and interactions with unprecedented precision," says Associate professor Anniina Färkkilä, the corresponding author of the study.

Tumor genes trick the immune system

"By studying individual cells directly in the tissue, we demonstrated how cancer cells hide in different ways, depending on the specific gene mutation. We found that the body's immune system is more effective against tumors with a mutation in BRCA1/2 genes. By contrast, tumors without such mutations have a connective tissue barrier prohibiting the interaction between the cancer and immune cells," says doctoral researcher Inga-Maria Launonen, BM.

BRCA1/2 mutations occur in approximately 20% of poorly differentiated serous carcinomas, the most common form of ovarian cancer. The killer T-cells closely guarded the aggressive tumor cells particularly in tumors with BRCA1/2 mutations, which is why these patients had a markedly better prognosis.

"By increasing our understanding of how tumor genes trick the immune system, we will be able to develop more effective ways to activate the body's own immune defenses to kill the cancer cells," Inga-Maria says.

Results will promote the tailoring of precision therapies

The results of the study confirm the significance of the interaction between tumor and immune cells in identifying new and more effective therapies as well as in choosing the right therapy for each patient.

"Our findings will enable us to tailor precision immuno- and combination therapies that have the potential to even cure ovarian cancer in the future," Färkkilä says.

Six Day Treatment Eradicates Advanced OC and Colorectal Cancer in 100% of Animals

(This article was written by Jade Boyd from Rice University's Office of Public Affairs.)

Bioengineers have shown they can eradicate advanced-stage ovarian and colorectal cancer in mice in as little as six days with a treatment that could be ready for human clinical trials later this year.

The treatment and animal test results are described online today in a Science Advances study co-authored by Omid Veiseh, Amanda Nash and colleagues from Rice, the University of Texas MD Anderson Cancer Center, the University of Virginia and others.

Veiseh, an assistant professor of bioengineering whose lab produced the treatment, said human clinical trials could begin as soon as this fall because one of his team’s key design criteria was helping cancer patients as quickly as possible. The team chose only components that had previously proven safe for use in humans, and it has demonstrated the safety of the new treatment in multiple tests.

“We just administer once, but the drug factories keep making the dose every day, where it’s needed until the cancer is eliminated,” Veiseh said. “Once we determined the correct dose — how many factories we needed — we were able to eradicate tumors in 100% of animals with ovarian cancer and in seven of eight animals with colorectal cancer.”

In the newly published study, researchers placed drug-producing beads beside tumors and within the peritoneum, a sac-like lining that supports intestines, ovaries and other abdominal organs. Placement within this cavity concentrated interleukin-2 within tumors and limited exposure elsewhere.

“A major challenge in the field of immunotherapy is to increase tumor inflammation and anti-tumor immunity while avoiding systemic side effects of cytokines and other pro-inflammatory drugs,” said study co-author Dr. Amir Jazaeri, professor of gynecologic oncology and reproductive medicine at MD Anderson. “In this study, we demonstrated that the ‘drug factories’ allow regulatable local administration of interleukin-2 and eradication of tumor in several mouse models, which is very exciting. This provides a strong rationale for clinical testing.”

Interleukin-2 is a cytokine, a protein the immune system uses to recognize and fight disease. It is an FDA-approved cancer treatment, but Nash, a graduate student in Veiseh’s group and the study’s lead author, said the drug factories provoke a stronger immune response than existing interleukin-2 treatment regimens because the beads deliver higher concentrations of the protein directly to tumors.

“If you gave the same concentration of the protein through an IV pump, it would be extremely toxic,” Nash said. “With the drug factories, the concentration we see elsewhere in the body, away from the tumor site, is actually lower than what patients have to tolerate with IV treatments. The high concentration is only at the tumor site.”Nash said the same general approach used in the study could be applied to treat cancers of the pancreas, liver, lungs and other organs. The drug factories could be placed next to tumors and within the linings that surround those organs and most others, she said. And if a different cytokine is needed to target a specific form of cancer, the beads can be loaded with engineered cells that make that immunotherapeutic compound.

The bead’s outer shell shields its cytokine-producing cells from immune attacks. The shells are made of materials the immune system recognizes as foreign objects but not as immediate threats, and Veiseh’s lab leveraged that in its design.

“We found foreign body reactions safely and robustly turned off the flow of cytokine from the capsules within 30 days,” he said. “We also showed we could safely administer a second course of treatment should it become necessary in the clinic.”

Avenge Bio , a Massachusetts-based startup co-founded by Veiseh, has licensed the cytokine-factory technology from Rice.

Additional co-authors include Maria Jarvis, Samira Aghlara-Fotovat, Sudip Mukherjee, Andrea Hernandez, Andrew Hecht, Yufei Cui, Shirin Nouraein, Jared Lee, David Zhang and Oleg Igoshin of Rice; Peter Rios, Sofia Ghani, Ira Joshi and Douglas Isa of CellTrans Inc.; Chunyu Xu and Weiyi Peng of the University of Houston; Rahul Sheth of MD Anderson; and José Oberholzer of both CellTrans Inc. and the University of Virginia.

The research was funded by the Cancer Prevention Research Institute of Texas (RR160047), Avenge Bio, the Emerson Collective, the Welch Foundation, the Rice University Academy of Fellows, the National Science Foundation (1842494) and the National Institutes of Health (R01DK120459).
Jazaeri receives compensation as a consultant on Avenge Bio’s scientific advisory board and has disclosed the relationship to MD Anderson in accordance with its conflict-of-interest policy. Nash, Jarvis, Aghlara-Fotovat, Mukherjee, Hecht, Igoshin, Zhang and Veiseh declared interests via patents filed by Rice on the cytokine factories. Igoshin, Veiseh and Oberholzer are paid consultants for Avenge Bio. Nash, Zhang, Sheth, Oberholzer, Jazaeri and Veiseh hold equity in Avenge Bio.

New drug combination effective for patients with advanced ovarian cancer

 This article is taken from ScienceDaily.

A new study led by researchers at Yale Cancer Center and the University of Maryland Comprehensive Cancer Center shows ixabepilone plus bevacizumab (IXA+BEV) is a well-tolerated, effective combination for treatment of platinum/taxane-resistant ovarian cancer compared to ixabepilone (IXA) alone. The data shows it also may significantly extend both progression free survival and overall survival. The results were published in the British Journal of Cancer.

"Novel approaches for relapsed ovarian cancer are desperately needed as limited effective combinations currently exist to treat our patients. The results of this study demonstrated a drug combination that may be an effective treatment for this type of ovarian cancer," said Alessandro Santin, MD, Professor of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine and Disease Aligned Research Team Leader for the Gynecological Cancers Program at Yale Cancer Center and Smilow Cancer Hospital and senior author of the study.

Ovarian cancer is the most lethal gynecologic malignancy. According to the American Cancer Society, nearly 20,000 women will be diagnosed with ovarian cancer in the United States every year, and more than 12,000 women will die from the disease. IXA is a microtubule-stabilizing agent that may be beneficial in patients treated with platinum/paclitaxel. Bevacizumab (BEV) is an antibody that keeps new blood vessels from forming and has shown clinical activity in ovarian cancer.

In this phase II study, researchers randomly assigned 78 patients to receive IXA+BEV or IXA alone. The primary endpoint was progression-free survival (PFS), Overall survival (OS), safety, and response rates served as secondary endpoints. Researchers also examined whether the presence of the protein TUBB3 within the tumor could predict clinical response to these drugs. Among 76 evaluable patients who received IXA+BEV compared to IXA, the response rate was 33% versus 8%, with clinical benefit durable at 6 months in 37% and 3%. The addition of BEV significantly improved both PFS (5.5 months vs 2.2 months) and OS (10 months vs 6 months). Both regimens were well-tolerated.

"We expect our findings to have major implications in the field of gynecologic oncology since they add a new, effective treatment for these extremely challenging tumors for which there are otherwise few options," said first author Dana M. Roque, MD, Associate Professor of the Division of Gynecologic Oncology at the University of Maryland School of Medicine and member of the Marlene & Stewart Greenebaum Comprehensive Cancer Center.

This article was published by Yale School of Medicine.

OncLive presents: "Latest Perspective in Ovarian Cancer Care"

 

OncLive presents "Latest Perspective in Ovarian Cancer Care". Below are the topics that will be covered. Here is the link to watch this on-demand video.

Agenda Topics

 

The closer we look, the further we’ll go
Highlighting the current state of ovarian cancer and current treatments to understand the challenges faced by those living with ovarian cancer. 

What if the treatments were as unique as the tumor?
Understanding the history of where we’ve been with ovarian cancer, and what’s in store for the future, and your role in it.

To test is to know what to target
Exploring the advances in genomic profiling of ovarian cancer tumors and optimizing treatment outcomes for patients.

Using the journey to define the destination
Applying personalized treatments in practice and the impacts these can have on those living with ovarian cancer.

Ovarian Cancer Chemotherapy Resistance Linked to Gene Expression

 This article is from the Clearity Foundation website. 

A team led by researchers at the University of Helsinki has uncovered stress-related tumor and microenvironment gene expression features that appear to coincide with chemotherapy resistance and shorter progression-free survival in individuals with high-grade serous ovarian cancer.

The results, published in Science Advances on Wednesday, suggest that it may eventually be possible to better detect and manage those at risk of progression after chemotherapy treatment.

“Our findings help to identify already, prior to treatment, the tumors that are the most likely to have a poor response to therapy,” co-senior and co-corresponding author Anna Vähärautio, a researcher at the University of Helsinki, said in a statement. “Our results also suggest that therapies could be targeted at the inflammatory microenvironment of cancer cells and the surrounding tissue to improve treatment outcomes with the help of combination therapy.”

Vähärautio and her colleagues searched for transcriptome features corresponding with resistance to neoadjuvant chemotherapy using single-cell RNA sequence profiles for nearly 51,800 tumor, stromal, or immune cells from high-grade serous ovarian cancer samples collected prospectively from 11 patients at Turku University Hospital. They also considered RNA in situ hybridization data for 10 of the matched pre- and post-treatment tumor sets, along with bulk RNA-seq data for dozens more paired pre- and post-treatment or pre-treatment and relapse samples.

The team analyzed RNA-seq profiles in pre-treatment diagnostic laparoscopy samples and in post-chemotherapy samples obtained after debulking surgery using a computational method called PRIMUS that was designed to dial down patient-specific features to find shared transcriptional signals linked to chemotherapy response.

In ovarian cancer patients with chemotherapy-resistant tumors primed to progress to metastasis, they found a rise in stress-associated cell features that had been present in baseline samples.

“The stress-associated state exists before chemotherapy, is subclonally enriched during the treatment, and associates with poor progression-free survival,” the authors reported. “Co-occurrence with an inflammatory cancer-associated fibroblast subtype in tumors implies that chemotherapy is associated with stress response in both cancer cells and stroma, driving a paracrine feed-forward loop.”

Those results lined up with patterns found in another 271 individuals with ovarian cancer who had their pre-treatment tumors tested by bulk RNA-seq through the Cancer Genome Atlas project, the researchers reported. Along with available gene expression profiles, they used reverse-phase protein array testing to distinguish between cases with stress-high or stress-low tumors.

That group included 86 individuals with high-grade serous ovarian tumors classified as stress-high and 144 individuals with stress-low tumors, the team noted. While the median progression-free survival time was 21.2 months for patients with stress-low tumors, it dropped to just shy of 15 months in the subset of patients with ovarian tumors showing high levels of stress-associated features.

With expression profiles for more than a dozen immune or stromal cell types that turned up in the tumor microenvironment samples, meanwhile, the researchers found related inflammation and paracrine signaling in stromal cells in the microenvironment of tumors showing stress-associated features, along with enhanced representation of cancer-associated fibroblast cells.

Based on these and other findings, the authors suggested that “a combination of induced and selective processes” contribute to the transcriptomic changes detected following chemotherapy — shifts that may be influenced by everything from tumor microenvironment features to differences in an individual’s underlying genetics and biology.

“[T]he identification of [a] stress signature opens avenues for combinatorial drug testing in preclinical models that maintain both subclonal heterogeneity and paracrine tumor-stromal signaling,” they concluded. “As many drugs targeting inflammatory effectors are already in clinical use for other indications, they may offer a realistic option for safe combinatorial therapies with a wide array of currently used oncological drugs to restrain the broadly adaptive stress response of tumors.”

This article was published by Genome Web.

The State of Ovarian Cancer: Exploring the Landscape of Systemic Therapy from OncLive

 

This video is worth reshowing in case you missed it.

Clearity Foundation: Help in Finding Clinical Trials

 

The Clearity Foundation has put together a search option to help you and your doctor select the best clinical trial for you. A link to that is below. If you haven't spent any time on the Clearity Foundation website, I would urge you to do so. It provides free counseling to women with OC and articles about research and links to treatment decision supports and what to do if you're newly diagnosed. 

In regards to finding clinical trials, there is a seven minute video tutorial that they have published on finding clinical trials You can find a link to this video here.

As per Clearity Foundation, "To find clinical trials, please check out the ovarian cancer-specific Trial Finder that Clearity has developed. The search outputs trials for which the patient is most likely to be eligible based on answers to questions about their specific clinical situation (e.g., prior treatments, tumor histology, platinum status), tumor biology, and preferences."