On December 8, 2023 City of Hope, one of the largest cancer research and treatment organizations in the United States, reported that it will present innovative research at this year’s San Antonio Breast Cancer Symposium (SABCS), taking place Dec. 5 to 9 in San Antonio, Texas (Press release, City of Hope, DEC 8, 2023, View Source [SID1234638353]).

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Each year, about 10,000 physicians, scientists and other health care professionals attend the annual conference, which examines new breast cancer research and helps guide treatment of patients nationwide. It is the largest and most prestigious scientific gathering on breast cancer research.

Research presented by City of Hope doctors and scientists includes:

Study: Data shows that taking estrogen reduces breast cancer risk in postmenopausal women who had a hysterectomy

Data from the Women’s Health Initiative (WHI) in 2002 had this finding: Women without a uterus who took estrogen and progesterone, hormone replacement therapy that women took to help prevent health problems caused by menopause, had an increased risk of breast cancer compared to those women in the study who took a placebo. The use of hormone replacement therapy dropped drastically. Women who had a uterus and only took estrogen had a lower incidence of breast cancer compared to women who took the placebo, but those findings were challenged and have been debated since then.

City of Hope’s Joanne Mortimer, M.D., director of the Women’s Cancers Program, Baum Family Professor in Women’s Cancers and vice chair/professor, Department of Medical Oncology & Therapeutics Research, and other breast cancer doctors and scientists from other institutions decided to take a deeper dive into those findings. They gathered data from nine other smaller studies of women who had a hysterectomy and took estrogen to compare those results with WHI data, which now tracks breast cancer incidence after more than 20 years of data collection.

The analysis of 7,339 women showed a lower risk of developing breast cancer among the women with no uterus who took estrogen compared with those who took a placebo. However, hormone replacement therapy did not strongly protect women in the studies against such menopause-related health complications as cardiovascular disease and brain health.

"Postmenopausal women who took a combination of estrogen and progesterone have a higher risk for developing breast cancer," said Mortimer, who will present the research at SABCS. "This study shows that single agent estrogen is safe in the population of women who have undergone hysterectomy and who desire hormone replacement therapy."

The abstract titled "Randomized trials of estrogen-alone and breast cancer incidence: a meta-analysis" was presented Dec. 6 in an oral presentation spotlight.

Findings from City of Hope’s innovative Couples Coping With Cancer Together program

Research from City of Hope’s innovative Couples Coping With Cancer Together program, started by the Department of Supportive Care Medicine, is one of the only programs of its kind nationwide, and is offered as part of the normal continuum of care provided to patients and families at City of Hope. It is tailored to the unique needs of English and Spanish-speaking couples facing a cancer diagnosis together, regardless of sexual orientation or relationship status.

As part of the supportive cancer care program, metastatic breast cancer patients and their partners completed a biopsychosocial screening, which asks each person about their perception of the patient’s prognosis. In addition, the couples were offered a standardized couples’ session before the medical consultation, individual couples’ counseling and a strengths-based group intervention.

The study included 241 patients and their partners. It found that patients were more realistic about their prognosis than their partners.

"Because open communication is important among women being treated for metastatic breast cancer and their partners, a prognosis question for both the patient and her partner should be included in standard of care," said Mortimer, who presented the research at SABCS. "This will also help couples prepare for advanced care planning."

The abstract titled "The ‘Couples Coping with Cancer Together Program’ provides insight into individual’s distress and an opportunity to discuss prognosis in a manner that is normalized as standard of care" was presented Dec. 7 in a poster session.

Testing for genetic mutations that can cause breast cancer

Because African American and Latina women have been less likely to undergo germline testing, which detects inherited genetic mutations that may cause cancer, it has been difficult to determine the prevalence of hereditary breast cancer predisposition in these populations.

Mortimer and team analyzed the prevalence of BRCA1/2 mutation in patients with a breast cancer diagnosis from City of Hope’s Implementing Next-generation Sequencing for Precision Intervention and Risk Evaluation (INSPIRE) study.

Patients with a history of any stage breast cancer were approached for their consent to undergo germline testing for 155 predisposition genes for cancer, which is performed at no cost to the patient.

From July 2020 to April 2023, 2,413 women underwent germline testing. Mutations in BRCA1 were identified in 3% of Hispanic women compared with 1.7% of non-Hispanic women. BRCA2 mutations were identified in 2.2% of Hispanics and 3% of non-Hispanics.

Hispanic women with breast cancer were 2.49 times as likely as non-Hispanics to carry a pathogenic germline BRCA1 mutations than BRCA2.

Women who have BRCA1 tend to have more aggressive breast cancers and the mutation can also cause ovarian cancer.

"What this study demonstrated is that regardless of your race, your ethnicity or age, everybody should have genetic testing," Mortimer added. "Because knowing what your BRCA status is has implications for surgery, prognosis and treatment."

"Prevalence of BRCA1/2 mutations in an underrepresented population of women with breast cancer: Observations from the City of Hope INSPIRE study" was part of a poster presentation on Dec. 7.

On December 8, 2023 Intensity Therapeutics, Inc. (Nasdaq: INTS), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that safety, tolerability, efficacy and immune activation data from the company’s Phase 2 INVINCIBLE trial of INT230-6 in patients with early-stage breast cancer without chemotherapy was presented at a Podium Poster Spotlight discussion session today during the 2023 San Antonio Breast Cancer Symposium (SABCS) (Press release, Intensity Therapeutics, DEC 8, 2023, View Source [SID1234638352]). Information on the presentation is below.

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Concurrent Poster Spotlight Session Block #6
PS16 Enhancing Immunotherapy for Triple Negative Breast Cancer: Novel Therapies and Biomarkers
Moderator: Hope S. Rugo, MD, FASCO, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California
Title: Intra-tumoral dosing of INT230-6 in early-stage breast cancer patients induces tumor cell necrosis and immunomodulatory effects: A phase II randomized window-of-opportunity study – the INVINCIBLE trial
Presentation #: PS16-03
Date and Time: Friday, December 8, 7:00 – 8:00 a.m. CT
Location: Stars at Night Ballroom 3 & 4
Presenter: Angel Arnaout, M.D., MSc, Ottawa Hospital Research Institute, Ontario Institute for Cancer Research
Discussant: Sangeetha Reddy, M.D., M.S.C.I., UT Southwestern Medical Center, Dallas, Texas

Copies of the presentation materials are available on Intensity’s website on the publications, papers and posters page.

"A large unmet need in the treatment of breast cancer is that the majority of breast cancers are immune quiescent; resulting in minimal response to immunotherapies. INT230-6 has the potential to fill this unmet need for multiple subtypes, including triple negative breast cancer, through its unique multiple anti-cancer mechanisms of action that cause tumor cell necrosis, ignition of an anti-cancer immune-based activation, increasing the diversity of the T-cell repertoire systemically that can enter into the tumor and its microenvironment," said Angel Arnaout, M.D.,MSc., Breast Surgical Oncologist at the Ottawa Hospital, Scientist at the Ottawa Hospital Research Institute, Professor of Surgery at the University of Ottawa and Co-Lead of the Ontario Institute for Cancer Research’s Window-of-Opportunity Network. "The ability for INT230-6 to induce necrosis and noted immune effects prior to a patient’s surgery, while maintaining a favorable safety profile, would be a major move forward for the treatment paradigm of breast cancer and potentially many other cancers."

"I am encouraged by the immune-related data being reported and the potential of INT230-6 as a presurgical treatment for women suffering from early-stage breast cancer," said Melanie Spears, Ph.D., Co-Director of Diagnostic Development and Co-Lead of the Window-of-Opportunity Network at the Ontario Institute for Cancer Research. "The localized effect of increased CD4 T-cells and NK cells within injected tumors and systemically increased T-cell diversity from baseline in these patients is quite interesting and remarkable for a locally-delivered therapy."

The INVINCIBLE Trial is a Phase 2, randomized study that enrolled women with newly diagnosed, operable early-stage intermediate or high-grade T1-T2 invasive breast cancers 2 to 5 weeks prior to surgery (lumpectomy or mastectomy). Drug dose was set by the diameter of the tumor. Subjects were randomly allocated (2:1) prior to resection to 1-3 IT injections of INT230-6 versus either no treatment (part 1 N=29) or saline sham injection (part 2 N=58). Several markers normally associated with systemic treatment were evaluated.

Efficacy Data:
The INVINCIBLE Phase 2 trial of INT230-6 demonstrated a high order of necrosis in presurgical breast cancer tumors in the period from diagnosis to surgery, with some patients in the Phase 2 study experiencing greater than 95% necrosis of the tumor. A functional pathway enrichment analysis was conducted and confirmed positive changes in T-cell activation, lymphocyte activation and inflammatory response. Further, INT230-6 treated patients experienced differential gene expression with an increase in median clonal diversity compared to baseline as well as significant changes in the immune cell composition, including CD4 T-cell and NK cells.

Safety Data:
Data show that INT230-6 has a favorable safety profile and is well tolerated. Over 95% of treatment-emergent adverse events (TEAEs) were low grade 1 or 2 primarily localized pain, fatigue, and nausea.

"We continue to be impressed with the safety and efficacy of INT230-6. Today’s news about the increase in mean systemic T-cell clonal diversity is truly exciting because it is a signal of the strength of adaptive immune response systemically. We believe that the ability to cause large levels of necrosis on a single dose of our locally-delivered drug with immune effects in a relatively cold cancer type such as breast cancer prior to surgery shortly after diagnosis is truly a new weapon in the war on cancer," said Lewis H. Bender, President and Chief Executive Officer of Intensity. "In addition to our anticipated Phase 3 program in metastatic sarcoma using INT230-6 as a monotherapy, we are underway in our preparations for a Phase 2/3 clinical program to test INT230-6 in combination with standard of care neoadjuvant therapy. We see the potential opportunity for our technology and drug products in both the metastatic and presurgical settings for many types of cancers."

About T-Cell Repertoire
The adaptive immune system is one of the body’s most powerful defenses. By being able to adapt, the body’s immune cells can be trained to attack undesirable cells or viruses anywhere in the body. T-cells are an important systemic component of the adaptive immune system that aid in the destruction of invaders. Immune repertoire refers to all the unique T-cell receptor (TCR) and B-cell receptor (BCR) genetic rearrangements. Only lymphocytes that encounter an antigen with the right receptor to bind to it will be activated and proliferate during an immune response, forming a clone of cells with identical antigen receptors for attack. A greater diversity of T-cell repertoire means there is higher likelihood for a T-cell to bind to the foreign entity (e.g. cancer cells) and increase the specific T-cell clonal population to destroy the invader.

About INT230-6
INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is composed of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor resulting in a favorable safety profile. In addition to local disease control, direct killing of the tumor by INT230-6 releases a bolus of neoantigens specific to the patient’s malignancy, leading to engagement of the immune system and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression that so often occurs with systemic chemotherapy.

On December 8, 2023 iOnctura, a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways, reported clinical results for roginolisib, a first-in-class oral allosteric modulator of PI3Kδ, presented at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2023 in Geneva (Press release, iOnctura, DEC 8, 2023, View Source [SID1234638350]).

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Roginolisib is in development for solid and hematologic malignancies including uveal melanoma, a rare cancer of the eye. The poster presentation titled ‘Safety and clinical efficacy of Roginolisib (IOA-244), the first oral allosteric modulator of phosphoinositide 3-kinase inhibitor delta (PI3Kδ)’ demonstrated that roginolisib continues to be well tolerated over long periods of treatment and continues to show a favourable trend in overall survival exceeding the overall survival previously reported with immune checkpoint inhibitors.

Mass cytometry data showed treatment with roginolisib led to an increase in activated anti-cancer CD8+ T-cells and natural killer (NK) cells, increased interferon signalling and a decrease in cancer-promoting Regulatory T-cells. This shifts the balance of the immune system enabling a more-effective attack on cancer. Boosting of antitumoral immunity was observed in patients with long-term disease control after roginolisib treatment but not patients with progressive disease.

An exploratory analysis from a patient with uveal melanoma outlined the potential of radiomics, an advanced AI driven analysis of imaging data, as a way of tracking changes in cancer lesions over time in addition to standard RECIST measurements.

Overall, these findings are consistent with prior studies in pre-clinical models and support the development of roginolisib in uveal melanoma and other malignancies with immune suppressed conditions.

Catherine Pickering, Chief Executive Officer of iOnctura, said: "These safety and clinical efficacy data demonstrate iOnctura’s progression of roginolisib. Our first-in-class allosteric modulator of PI3Kδ continues to show a favourable trend in overall survival and is well tolerated over very long periods of treatment, now up to 38 months in patients with uveal melanoma. An exploratory readout also shows that patients who respond well to roginolisib, with prolonged stabilisation of their disease, exhibit signs of an activated immune system better able to fight the tumor. We eagerly anticipate a final clinical readout in 2024."

On December 8, 2023 Aster Insights, the leading provider of scientific and clinical intelligence for oncology discovery, reported upcoming research presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s (ASH) (Free ASH Whitepaper) 65th Annual Meeting, December 9-12 in San Diego, CA (Press release, Aster Insights, DEC 8, 2023, View Source [SID1234638349]).

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Three abstracts will be shared at this year’s ASH (Free ASH Whitepaper) meeting by Moffitt Cancer Center, which co-founded the Oncology Research Information Exchange Network (ORIEN) in 2006. The investigations all utilize patient data from Aster Avatar, the best-in-class, deepest multimodal dataset for discovery research in oncology.

The schedule of presentations and highlights include:

Rafael Renatino-Canevarolo, PhD, Ex Vivo Mathematical Myeloma Advisor (EMMA) – a Clinical, Molecular, and Phenotypic Platform to Tailor Personalized Therapeutic Strategies for Multiple Myeloma (abstract 2280)
Presentation time: Saturday, December 9, 2023, 5:30 PM-7:30 PM

Examining the impact of a state-of-the-art platform for clinical-informed decisions, research advancement, and preclinical compound testing called the "Ex Vivo Mathematical Myeloma Advisor" (EMMA) on drug discovery and understanding of drug interaction for multiple myeloma patients.

Praneeth Reddy Sudalagunta, PhD, Selinexor Disrupts Epigenetic Programing and Modulates Immunogenicity in Multiple Myeloma (abstract 3301)
Presentation time: Sunday, December 10, 2023, 6:00 PM-8:00 PM

Investigating the cellular mechanisms of Selinexor (SELI) resistance leading to an immunogenic cell state.

Ciara L. Freeman, PhD, MSc, FRCPC, MRCP, Single Cell RNA Sequencing of Sequential Samples before and after BCMA-Directed CAR-T Reveal Features Associated with Non-Durable Response, Exhausted T-Cells and Decreased Expression of Genes Encoding Key Surface Targets in Particular in Patients with Extramedullary Disease (abstract 3304)
Presentation time: Sunday, December 10, 2023, 6:00 PM-8:00 PM

Longitudinal single cell analysis to identify factors associated with response, or therapeutic failure, to FDA approved anti-B-cell maturation antigen (BCMA) directed CAR-T cell therapy.

"ASH is a unique opportunity to demonstrate the impactful discoveries resulting from ORIEN and Aster Insights’ discovery solutions," said Anand Shah, MD, Aster Insights CEO. "This year, we are proud to showcase our collaborative work with Moffitt Cancer Center’s scientists that continues to push the envelope of multiple myeloma research and patient care."

On December 8, 2023 SkylineDx, an innovative diagnostics company focused on research & development of molecular diagnostics reported the release of new data during the American Society of Hematology (ASH) (Free ASH Whitepaper) 2023 Annual Meeting (Press release, SkylineDx, DEC 8, 2023, View Source [SID1234638348]). Dr. Noa Biran, Associate Professor at Hackensack Meridian School of Medicine, will present two posters from the pioneering US study on risk assessment in multiple myeloma. These studies were conducted within the PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) trial, which aim to assess the impact of SKY92 on risk stratification and treatment decisions in clinical practice for newly diagnosed multiple myeloma patients. Multiple Myeloma (MM) is a complex hematologic malignancy marked by genetic instability, variable survival rates, and diverse treatment responses. The SKY92 gene expression profiling (GEP) assay is a valuable tool for stratifying MM patients into high-risk and standard-risk groups for disease progression and survival. Despite advances in MM treatments, a subset of high-risk patients still faces limited benefits from current therapies. This study aims to assess risk classification based on conventional risk markers and the SKY92 risk classifier, providing insights for optimizing risk-adapted treatment.

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A total of 251 MM patients were enrolled in this prospective US multicenter trial. The results based on prospective real-world clinical data show significant differences in progression-free survival (PFS) and overall survival (OS) between SKY92 standard-risk and high-risk patients, confirming SKY92’s reliability as a prognostic marker.

Integrating R-ISS staging with SKY92 classification, as previously reported [Kuiper et al. 2020], resulted in three risk groups. This combined classification method identified a larger number of high-risk patients with a significantly shorter OS and PFS when compared to the R-ISS alone.

The trial results reveal a significant discrepancy between risk stratification derived from conventional clinical practice assessments and that determined by SKY92. Integration of SKY92 into clinical practice enables the identification of a subset of high-risk patients characterized by substantially shorter PFS and OS. These findings support the added value of integrating SKY92 into clinical practice for precise risk assessment of patients. Furthermore, the integration of SKY92 resulted in increased physician confidence in assessing patient risks.

Jvalini Dwarkasing, Chief Scientific Officer of SkylineDx, expressed the company’s enthusiasm for these presentations, saying, "At SkylineDx, our mission is to advance the field of hematological diagnostics and ultimately improve patient care. We are proud that Dr. Biran will be presenting the insights from these groundbreaking studies that have the potential to transform the way we understand and treat hematologic disorders."

Dr. Noa Biran’s presentations at ASH (Free ASH Whitepaper) 2023 promise to challenge risk stratification in multiple myeloma, with implications for personalized treatment approaches and improved patient outcomes.