On May 25, 2022 The European Myeloma Network (EMN), an international collaborative network of expertise centers for multiple myeloma in Europe and Australia, and Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported the dosing of the first patient in the collaborative EMN29/XPORT-MM-031 study, a randomized, global Phase 3 study evaluating an all-oral regimen of selinexor, Karyopharm’s first-in-class, oral exportin 1 (XPO1) inhibitor, in combination with Pomalyst (pomalidomide) and low-dose dexamethasone (SPd) versus Empliciti (elotuzumab), pomalidomide, and dexamethasone (EPd) in patients with relapsed or refractory multiple myeloma (NCT05028348//EMN29) (Press release, Karyopharm, MAY 25, 2022, View Source [SID1234615031]).

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The Phase 3, two-arm, randomized, active comparator-controlled, open-label, multicenter study will compare the efficacy, safety, and the impact on health-related quality of life of SPd versus EPd in pomalidomide-naïve patients with relapsed or refractory multiple myeloma. Patients will have received one to four prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 monoclonal antibody (mAb), prior to being enrolled in the study. Final dosing for the selinexor arm at 40 mg or 60 mg will be determined following an interim analysis of data from the first 60 patients. The primary endpoint of the study is progression-free survival (PFS). The study is sponsored by the European Myeloma Network and is expected to recruit approximately 280 patients.

"Despite the progress made in treating multiple myeloma, new treatment options remain a critical need as the majority of patients will relapse and eventually stop responding to current therapies," said Reshma Rangwala, MD, PhD, Chief Medical Officer at Karyopharm Therapeutics. "We look forward to collaborating with the EMN on this important study. We have encouraging data in patients who have been treated with an anti-CD38 based regimen and we are eager to see the result in this patient population."

"We are extremely pleased to have this important study underway and look forward to further elucidating the potential of the SPd triplet regimen for Multiple Myeloma patients," added Professor Katja Weisel, Deputy Director of the University Cancer Center in Hamburg (UCCH) and principal investigator of the EMN29/XPORT-MM-031 study. "We look forward to the top-line results in 2024."

The initiation of this Phase 3 study follows encouraging data from an all-oral arm of the Phase 1b/2 STOMP study (NCT02343042) and the Phase 2 study XPORT-MM-028 (NCT04414475) in which selinexor was evaluated in combination with Pomalyst and low-dose dexamethasone in patients with relapsed or refractory multiple myeloma who received at least two prior lines of therapy, including a PI and an IMiD.

About Multiple Myeloma

According to Clarivate Analytics, approximately 47,000 patients are diagnosed with relapsed or refractory multiple myeloma in the U.S. each year.1 It is most frequently diagnosed in people aged 65-74 years old.2 Despite recent therapeutic advances, there is currently no cure and most patients’ disease will typically progress following treatment with currently available therapies. According to the American Cancer Society, an estimated 12,640 deaths due to multiple myeloma are expected to occur in the U.S. in 2022.3

About EMN

The European Myeloma Network (EMN) is an international collaborative network of expertise centers for multiple myeloma in Europe and Australia, working together with many national cooperative groups. EMN is chaired by Professor Pieter Sonneveld and Professor Mario Boccadoro. It has offices in Rotterdam, the Netherlands and in Torino, Italy. EMN has organized more than 30 international prospective trials in multiple myeloma and related diseases in collaboration with international pharmaceutical companies. EMN strongly supports translational research in its trials, focusing on modes of action of the drugs under investigation.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea, Singapore and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including endometrial cancer and myelofibrosis. For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).

For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.

Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.

Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.

Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.

Serious Infection: Monitor for infection and treat promptly.

Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.

Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.

Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.

The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions were infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.

On May 25, 2022 Agendia, Inc., a commercial-stage company focused on improving outcomes for breast cancer patients worldwide by providing physicians and patients with next-generation diagnostic and information solutions to inform optimized treatment decision-making, reported 10,000 patients have been successfully enrolled in the FLEX Registry (Press release, Agendia, MAY 25, 2022, View Source [SID1234615047]). Agendia’s unique FLEX Registry is a real-world, large-scale, prospective, observational breast cancer study (NCT03053193) intended to enable the discovery of novel genomic profiles to improve precision in the management of breast cancer.

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The FLEX Registry’s groundbreaking approach to cancer research is accelerating impactful data generation with its patient-centric design and national network of participating sites, allowing its investigator-initiated sub-studies to produce critical results that drive science forward. Six posters based on data from FLEX will be presented at ASCO (Free ASCO Whitepaper) 2022, one of which will be a poster discussion session.

"When we developed the idea for FLEX, we knew it was essential for breast cancer care but did not immediately expect this high level of engagement of the medical community in this real-world data trial," said Bastiaan van der Baan, Chief Clinical and Business Development Officer at Agendia. "Because we blazed this trail, we are ahead in data collection and already producing actionable insights. We are so proud of the FLEX Registry, which allows not only for the gathering of whole transcriptomic data from valuable tumor samples, but also expands the power of genomic insights to physicians practicing in their communities. We look forward to further partnering with physicians to continue this valuable work, and believe FLEX will advance cancer care for the better."

Since its launch in April 2017, FLEX has enrolled patients at greater than 90 global study sites, including ten National Cancer Institute-designated comprehensive cancer centers. Participating sites also include community hospitals to ensure inclusion of diverse populations, especially those which are often underrepresented in traditional clinical trials. Additionally, the FLEX collaborative platform allows participating investigators the opportunity to author their own sub-study protocols, as approved by the FLEX Scientific Review Committee. To date, 38 investigator-initiated sub-studies have been approved, resulting in 30 published abstracts at major oncology conferences, including those to be shared at ASCO (Free ASCO Whitepaper) 2022.

"The massive dataset provided by the FLEX Registry has the potential to be one of the most impactful and representative prospective breast cancer studies in recent history," said Cynthia X Ma, MD, PhD, oncologist and FLEX national principal investigator at Washington University School of Medicine in St. Louis. "Not only will the data from FLEX be valuable to clinicians like myself, but to the millions of women with breast cancer seeking clarity, guidance, and evidence-based research throughout their journey. The broad and inclusive nature of FLEX translates into findings beyond data collection, allowing for several ongoing sub-studies to be conducted to uncover new, meaningful insights to inform personalized, precise breast cancer treatment plans."

The FLEX Registry has yielded potentially practice-changing data across a wide variety of questions researchers seek to answer about breast cancer. These include:

Insights from multiple sub-studies which showed clinical and molecular differences between tumors of African American and Caucasian patients with HR+ breast cancer;
An age-related sub-study of ER+ breast cancers from women over 50 compared to those 50 and younger showed there is no substantial difference in gene expression, suggesting any observed differences in response to therapy are determined more by genomic features than by age; and
A molecular subtype sub-study showed the gene expression patterns of high-risk ER+, BluePrint Basal breast cancers are much more like IHC triple negative breast cancers than other ER+ cancers.
"It is truly remarkable how rapidly the FLEX Registry was able to enroll 10,000 breast cancer patients especially in light of the COVID-19 pandemic, signifying the uptick in clinical momentum to better understand the real-world impact of genomic differences among women with breast cancer," said Joyce O’Shaughnessy, MD, Director, Breast Cancer Research, Baylor University Medical Center, Texas Oncology and the US Oncology Research Network in Dallas, TX. "Under a shared vision to improve patient outcomes via personalized treatment planning, Agendia, in partnership with clinicians and researchers, is leading the charge to capture robust and valuable data that has the potential to change the breast cancer treatment paradigm for women of all backgrounds and genomic subtypes."

Open to both women and men diagnosed with stage I, II, or III cancer, including all clinical subtypes, the dataset aims to be a true representation of the entire patient population. By capturing data from patients of all ethnicities, ages, genders, and health statuses, the FLEX database provides valuable opportunities to accelerate real-world breast cancer research and has the ability to enroll less prevalent patient populations on a larger scale. This enrollment strategy enables further investigation and the potential to provide targets for treatment optimization for those patients. FLEX is currently recruiting patients for sub-studies, including one prospective study that aims to assess treatment response differences of ER+ Basal-Type tumors, in comparison to Luminal tumors, to DNA-damaging neoadjuvant chemotherapy regimens.

"We’re extremely proud of this landmark achievement that brings us closer to meeting our 30,000-patient goal for total enrollment in the FLEX Registry," said William Audeh, MD, Chief Medical Officer at Agendia. "At Agendia, our main goal with FLEX is to utilize the extensive genomic information present within each breast cancer to better understand the differences between breast cancer subgroups, in both clinically-defined subtypes and diverse patient populations. The genome-level insights we obtain are connected to clinical data and help us understand differences in response to therapy and outcomes. In designing FLEX’s wide inclusion criteria, we’re enabling researchers to access critical genomic data in a pooled database from many centers — data that otherwise would have been challenging to gather via recruitment in standard clinical trials. This approach furthers our collective understanding of tumor biology, providing more specific insights to support treatment planning decisions for women with breast cancer."

After more than five years of collecting data, the FLEX Registry approaches a critical new phase of research in which Agendia will be able to generate outcomes-based analyses, develop interventional sub-studies, and extend the potential utility of liquid biopsy testing. With its centralized database, the FLEX Registry could be positioned to yield full transcriptome data to determine gene expression characteristics of tumors on a large scale, translating and qualifying these observations into clinically meaningful takeaways to help advise women with breast cancer throughout treatment planning.

On May 25, 2022 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported that an abstract demonstrating the ability of the Company’s DecisionDx-Melanoma test to risk-stratify patients with cutaneous melanoma according to their survival likelihood will be available online during the upcoming 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held virtually and in Chicago, June 3-7, 2022 (Press release, Castle Biosciences, MAY 25, 2022, View Source [SID1234615048]).

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Details are as follows:

Abstract Title: "Validation of the 31-gene expression profile test to stratify melanoma-specific survival in an unselected, prospectively tested cohort of patients with stage IIB-III cutaneous melanoma"
Abstract number: e21538
About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma (CM) metastasis or recurrence, as well as the risk of sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 6,300 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. Additionally, Castle has an ongoing collaboration with the National Cancer Institute (NCI) to link DecisionDx-Melanoma testing data with data from the Surveillance, Epidemiology and End Results (SEER) Program’s registries on CM cases. This collaboration has resulted in Castle’s analysis of 5,226 samples (clinically tested through December 31, 2018) in a study to evaluate melanoma-specific survival and overall survival; in this study, patients tested with DecisionDx-Melanoma had better survival rates than untested patients, and the data suggested that DecisionDx-Melanoma can accurately risk-stratify for disease progression to aid in risk-aligned treatment plans for improved patient outcomes and survival. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Additionally, impact on patient management plans for one of every two patients tested has been shown in five multi-center/single-center studies including more than 800 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. To predict risk of recurrence and likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an Integrated Test Result. Through March 31, 2022, DecisionDx-Melanoma has been ordered 97,288 times for patients with cutaneous melanoma.

On May 25, 2022 BlueSphere Bio, a T-cell receptor (TCR) T-cell therapy company developing a powerful TCR discovery platform and novel therapeutic candidates for patients with hematologic malignancies and solid tumors, reported that Sawa Ito, M.D., Ph.D., was selected to provide an oral presentation during the 2022 Joint ASTCT + EBMT Basic and Translational Scientific retreat (Press release, BlueSphere Bio, MAY 25, 2022, View Source [SID1234616065]). The retreat is a select gathering limited to 100 attendees focused on basic and translation biology in the field.

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The presentation will highlight the capabilities of the company’s TCXpress platform and its ability to rapidly clone TCRs against specific targets from single T cells. This work enabled the discovery of BlueSphere’s first clinical candidate, a TCR T-cell therapy directed against the minor histocompatibility antigen (miHA) HA-1. The company anticipates filing its first IND by the end of 2022. The TCXpress platform has also enabled the discovery of four new TCRs reactive against other relevant miHAs, in addition to HA-1. BlueSphere plans to announce details on these other targets later this year.

Title: High Throughput Cloning Reveals Diverse Properties of anti-HA-1 T Cell Receptors

Presenter: Dr. Sawa Ito, hematologist/oncologist at UPMC Hillman Cancer Center and Assistant Professor, Division of Hematology-Oncology and Department of Immunology at the University of Pittsburgh School of Medicine.

About TCXpress

TCXpress is a proprietary high-throughput and efficient T-cell receptor (TCR) capture, expression and functional screening platform capable of processing thousands of single T cells directly into functionally expressed TCRs within a matter of days, thereby creating extensive libraries without the need for sequencing or TCR gene synthesis.

On May 25, 2022 Leidos (NYSE: LDOS), a FORTUNE 500 science and technology leader, reported that will participate in the Jefferies Virtual IT Services Summit (Press release, Leidos, MAY 25, 2022, View Source [SID1234615033]).

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Chris Cage, Chief Financial Officer, will engage in a virtual question and answer "fireside chat" on Wednesday, June 1, 2022, at 11:00 a.m. ET.

A live audio webcast of the event will be available on the Leidos Investor Relations website at View Source A replay of the webcast will be available following the presentation at the same link listed above for 30 days afterward.