On May 24, 2024 Exact Sciences Corp. (Nasdaq: EXAS), a leading provider of cancer screening and diagnostic tests, reported that it will present 10 abstracts highlighting the breadth and depth of the company’s screening and diagnostic portfolio at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 31 – June 4, 2024, in Chicago, Ill (Press release, Exact Sciences, MAY 24, 2024, View Source [SID1234643673]). Presentations will include new data confirming both the predictive and prognostic value of the Oncotype DX Breast Recurrence Score test in racially and ethnically diverse patients. Exact Sciences will also present data on its approach to multi-cancer early detection (MCED) across multiple tumor types, plus additional real-world evidence showing optimized screening adherence strategies for the Cologuard test as well as high adherence rates for repeat screenings.

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"Exact Sciences’ growing evidence shows that earlier and more personalized treatment interventions lead to greater success for people living with cancer. Therefore, effective cancer screening and diagnostic tools are critical to improving patient outcomes," said Dr. Rick Baehner, Chief Medical Officer, Precision Oncology at Exact Sciences. "These data presented at ASCO (Free ASCO Whitepaper) support our goal to set new screening and diagnostic standards through rigorous innovation and real-world data collection across cancer care. We are committed to continuing to develop high-quality tests that meet the needs of all patients, regardless of race, age, or ethnicity."

Precision Oncology
New data from two studies evaluating Recurrence Score results showed that the Oncotype DX Breast Recurrence Score test predicted breast cancer survival across different racial and ethnic groups. The first study confirmed that the test is prognostic for breast cancer-specific mortality and predictive of chemotherapy benefit across racial and ethnic groups in lymph node-negative patients, following propensity score-adjusted analyses. This real-world study of more than 171,000 patients with nonmetastatic, hormone receptor-positive, HER2-negative breast cancer with a Recurrence Score result from the SEER database also showed that the Recurrence Score result was predictive of chemotherapy benefit across all node-positive patients. In the study, non-Hispanic Black patients were shown to have a higher Recurrence Score result and chemotherapy usage compared to other groups. Exploratory analyses of the RxPONDER trial showed that while the test remained prognostic across racial and ethnic groups, non-Hispanic Black patients had higher proliferation axis scores, suggesting that differences in tumor biology may help explain differences in breast cancer outcomes.

Screening
New data suggests benefits of multi-cancer early detection (MCED) in identifying cancers earlier, with patients having a shorter time to diagnosis and fewer late-stage (Stage IV) diagnoses. In a modeling analysis, when MCED was evaluated across 12 different cancer types, it resulted in fewer Stage IV diagnoses relative to diagnosis through usual care, with 38% of Stage IV reductions attributed to cancers without recommended screening guidelines.

Exact Sciences will also share real-world evidence showing high adherence and three-year repeat rate of the Cologuard test. It will also share data demonstrating success with using different digital outreach approaches to help improve screening adherence, leading to high screening completion rates for the Cologuard test across different patient populations.

Data presentations across Exact Sciences’ Precision Oncology and Screening portfolio at ASCO (Free ASCO Whitepaper) 2024:

Precision Oncology

Abstract 515: Recurrence Score Gene Axes Scores by Race and Ethnicity in the RxPONDER Trial
Presenter: Y. Abdou, MD
Session: Rapid Oral Abstract Session
Date/time: Friday, May 31, 3:39 PM – 3:45 PM CDT
Key findings: This study analyzed Recurrence Score gene axis scores and their associations with outcomes to understand the differences in underlying tumor biology among different racial and ethnic groups. Recurrence Score gene axis scores differed by race/ethnicity, with Non-Hispanic Black patients exhibiting higher proliferation axis scores than other groups. This could partially explain the poorer outcomes observed in this population in the RxPONDER trial. These findings highlight the importance of tumor biology and support further investigation into the intricate factors contributing to disparities in outcomes to address them effectively.

Abstract 533/Poster Bd 125: Updated SEER database study of 21-gene assay to assess breast cancer-specific mortality and benefit of chemotherapy by race and ethnicity
Presenter: E. Diego, MD
Session: Poster Session
Date/time: Sunday, June 2, 9:00 AM CDT
Location: Hall A
Key findings: Real-world evidence from the SEER registries in over 145,000 patients with breast cancer confirms that the Oncotype DX Breast Recurrence Score test is prognostic of breast cancer-specific survival across all racial and ethnic groups and predictive of chemotherapy benefit across most groups. This study was performed to further understand the racial and ethnic disparities identified in the TAILORx and RxPONDER phase 3 trials, which used the Oncotype DX test to identify patients with node-negative or node-positive breast cancer who may or may not benefit from chemotherapy. This latest SEER analysis provides further confidence in the prognostic value of the Oncotype DX test regardless of race or ethnicity.

Abstract 508: Development and validation of RSClin N+ tool for hormone receptor-positive (HR+), HER2-negative (HER2-) node-positive breast cancer
Presenter: L. Pusztai, MD, PhD, FASCO
Session: Oral Abstract Session
Date/time: Monday, June 3, 5:24 PM – 5:35 PM CDT
Location: Hall B1
Key findings: The RSClin N+ tool model delivers improved estimates of prognostic risk and absolute chemoendocrine therapy benefit over clinical or genomic data alone for patients with node-positive, HR+/HER2- breast cancer and could be used in patient counseling. Building upon the success of the RSClin tool, the N+ version of the RSClin tool integrates the Recurrence Score result with clinicopathologic factors, stratified by menopausal status, to further enhance its prognostic and predictive value for patients with node-positive disease.

Abstract 576/Poster Bd 168: Evaluating Ki67 and Oncotype DX Recurrence Score during neoadjuvant treatment with letrozole/abemaciclib or chemotherapy in highly proliferative HR+/HER2- breast cancer patients participating in the GEICAM CARABELA trial.
Presenter: A. Guerrero, MD
Session: Poster Session
Date/time: Sunday, June 2, 9:00 AM CDT
Location: Hall A
Key findings: Highly proliferative breast cancer tumors (Ki67 ≥40%) or those with high Recurrence Score results (>25) showed lower residual cancer burden after neoadjuvant chemotherapy treatment versus neoadjuvant letrozole plus abemaciclib. These data confirm the predictive value of Ki67 and Recurrence Score risk assessments and suggest that relying solely on letrozole/abemaciclib as a systemic treatment for these tumors may be insufficient. This is an exploratory analysis from the CARABELA phase 2 trial, which is comparing the efficacy of neoadjuvant chemotherapy vs. neoadjuvant letrozole/abemaciclib treatment in patients with HR+/HER2- breast cancer who are at high/intermediate risk (stage II-III, Ki67≥20%).

Abstract 565: Combination of predicted sensitivity to endocrine therapy (SET2,3 index) and the Recurrence Score in node-positive breast cancer: independent validation in the PACS-01 trial
Presenter: F.M. Penault-Llorca, MD, PhD
Session: Poster Session
Date/time: Sunday, June 2, 9:00 AM CDT
Location: Hall A
Key findings: Combining the Oncotype DX Breast Recurrence Score test with the Sensitivity to Endocrine Therapy (SET2,3) index, a biomarker-based assessment designed to assess a tumor’s response to hormonal therapy, successfully enhanced the prognostic value for patients with node-positive breast cancer. These are data from an independent, blinded validation analysis of the PACS-01 trial, which evaluated sequential adjuvant epirubicin-based and docetaxel chemotherapy for patients with node-positive breast cancer.

Abstract 10584/Poster Bd 111: Clinical and economic benefit of genomic testing strategies to guide the treatment of patients with HR+/HER2- breast cancer in the US
Presenter: B. Heald, MS
Session: Poster Session
Date/time: Monday, June 3, 1:30 PM CDT
Location: Hall A
Key findings: Using a testing strategy that combines both the Oncotype DX Breast Recurrence Score test and germline genetic testing (GGT), which identifies potentially pathogenic cancer variants, can help optimize treatment decisions in early HR+/HER2- breast cancer and improve patient outcomes at reduced costs, according to this health economic modeling study.

Screening

Abstract 11135/Poster Bd 330: Time-to-diagnosis and peri-diagnostic healthcare utilization between screen- and non-screen detected cancers: Evidence from SEER-Medicare
Presenter: X. Cao, PhD
Session: Poster Session
Date/time: Monday, June 3, 9:00 AM CDT
Location: Hall A
Key findings: Effective cancer screening programs successfully shortened the time to diagnosis and reduced the frequency of stage 4 diagnoses for patients with breast or colorectal cancer detected through screening. This retrospective SEER registry analysis reinforces that effective cancer screening technologies have the potential to improve patient outcomes by enabling earlier detection when treatment options are typically most successful.

Abstract 11076/ Poster Bd 271: Effect of multi-cancer early detection testing on late-stage cancers: A modeling study
Presenter: J. Chhatwal, PhD
Session: Poster Session
Date/time: Monday, June 3, 9:00 AM CDT
Location: Hall A
Key findings: In a 50-year modeling simulation, MCED testing resulted in 1,323 fewer Stage IV (24%) cancer diagnoses overall compared to usual care. Thirty-eight percent of these Stage IV reductions were attributable to screening for cancers without recommended guidelines, underscoring the potential of novel MCED strategies to help catch cancers earlier and initiate treatment interventions sooner.

Abstract e15632: Real-world multi-target stool DNA adherence in an underserved and vulnerable prison patient population.
Presenter: J. Kasselman
Session: Publication Only
Date/time: N/A
Location: N/A
Key findings: Among incarcerated persons, mt-sDNA yielded high adherence rates (95.3%) and short completion times (average of 20 days) in this difficult-to-reach population. These data further demonstrate the importance of efforts to uncover patient, provider, and system-level benefits that may be obtained through broader adoption of this highly accessible screening approach in this challenging healthcare setting.

Abstract e15633: Real-world multi-target stool DNA longitudinal adherence for colorectal cancer re-screening in a large, national population
Presenter: M. Greene
Session: Publication Only
Date/time: N/A
Location: N/A
Key findings: In a real-world longitudinal analysis of 481,748 patients, adherence to repeat colorectal cancer (CRC) screening with the Cologuard test remained high (83.6%), and patients who underwent repeat screening once were more likely to continue with a third lifetime Cologuard screening. These data suggest high perceived patient confidence in Cologuard, further reinforcing its potential to help close the CRC screening gap for average-risk individuals.

On May 24, 2024 Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for solid and liquid malignancies and inflammatory diseases based on its unique Mimicry platform, reported updated immune-monitoring and clinical data from the ongoing EOHNL1-20/SIDNEY trial evaluating EO2463 in monotherapy and in combination with lenalidomide and/or rituximab in indolent non-Hodgkin lymphoma (NHL) (Press release, Enterome, MAY 24, 2024, View Source [SID1234643672]). The results will be featured in a poster session on Monday, June 3rd, 2024, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, USA.

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"We are extremely encouraged by these results, which validate our OncoMimics approach to targeting liquid tumors," said Dr. Jan Fagerberg, Chief Medical Officer of Enterome. "In addition to the standalone activity seen with EO2463 during the first six weeks of treatment, the 78% complete response rate observed with the subsequent combination therapy supports our belief that EO2463 can significantly add to the patients’ care. Thanks to its unique safety and efficacy profiles, we believe EO2463 has the potential to become a valuable long-term treatment option for non-Hodgkin B cell lymphomas."

Pierre Bélichard, CEO of Enterome, added: "Building on the promising findings that are presented at ASCO (Free ASCO Whitepaper) 2024, we look forward to continuing the SIDNEY trial and reporting results from the monotherapy expansion cohort which focuses on the "watch-and-wait" setting. Despite a confirmed cancer diagnosis and being ultimately likely to progress to symptomatic condition, a large portion of patients with indolent Follicular Lymphoma and Marginal Zone Lymphoma are not receiving immediate treatment due to the absence of safe and effective therapies. EO2463 appears ideally suited to address this significant unmet medical need."

Key Highlights from the EONHL1-20/SIDNEY presentation, entitled Phase 1/2 of EO2463 immunotherapy as monotherapy and in combination with lenalidomide and/or rituximab in indolent NHL:

The Phase 1/2 EONHL1-20/SIDNEY evaluates the safety and preliminary efficacy of EO2463 as monotherapy and in combination with lenalidomide and/or rituximab for the treatment of patients with indolent NHL. Patients in cohort 1 received EO2463 once every two weeks for a total of four doses followed by once every four weeks for up to 15 doses. After 6 weeks of EO2463 monotherapy oral lenalidomide was added, and if no complete remission was achieved at week 19, rituximab was also included.

EO2463 was well-tolerated with no grade ≥3 related events in monotherapy (events attributed to EO2463 only were local administration site reactions and headache)
Metabolic marker/tumor size reduction observed in 4 of 9 patients (44%) at week 6 on EO2463 monotherapy
Complete Response rate in 7 of 9 patients (78%) achieved on combination therapy (response assessment per Lugano, 2014, and Lyric, 2016, Classifications), including 5 radiologic complete responses (56% radiologic CRs)
Expansion of specific CD8+ T cells against the OncoMimics peptides and targeted B cell antigens in a significant portion of patients with up to 5.3% of all peripheral blood CD8+ T cells being specific for OncoMimics peptides
Specific CD8+ T cells could be detected ex vivo early as well as in long-term follow-up, currently until 94 weeks after the study treatment start
On-target immune activation observed with cytotoxic T cells of memory phenotype, remaining polyfunctional long-term
Study ongoing with three extension cohorts:
EO2463 monotherapy in patients with newly diagnosed, previously untreated follicular lymphoma (FL) or marginal zone lymphoma (MZL), not in need of therapy ("watch-and-wait" setting)
EO2463 + rituximab (from week 7) in patients with newly diagnosed, previously untreated FL/MZL and low tumor burden, in need of therapy, and
EO2463 + lenalidomide (from week 1) + rituximab (from week 19) in patients with relapsed/refractory, previously treated FL/MZL

Presentation details:

Title: Phase 1/2 of EO2463 immunotherapy as monotherapy and in combination with lenalidomide and/or rituximab in indolent NHL (EONHL1-20/SIDNEY)

Presenting Author: J.C. C. Villasboas, M.D., Division of Hematology, Mayo Clinic

Session Name: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Session Date and Time: June 3rd, 9:00 AM-12:00 PM CDT

Abstract #7058 is available here and the Poster will be available on Enterome’s website following the session.

About Phase 1/2 SIDNEY

SIDNEY (EONHL1-20) is a Phase 1/2 multicenter, open-label, first-in-human study of EO2463 as monotherapy and in combination with lenalidomide and/or rituximab for the treatment of patients with indolent non-Hodgkin lymphoma (NHL). The study aims to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 monotherapy and combination therapy in approximately 60 patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL). For more information on the study, refer to Clinicaltrials.gov identifier: NCT04669171.

About Indolent non-Hodgkin lymphoma (iNHL)

Non-Hodgkin lymphoma is the seventh most common cause of new cancer cases among both men and women, accounting for 4% to 5% of new cancer cases, and 3% to 4% of cancer-related deaths. Indolent non-Hodgkin lymphoma (iNHL) constitutes a distinct subset where, even though currently available treatments are efficacious, the main disease subtypes, such as follicular lymphoma (FL) and marginal zone lymphoma (MZL), are considered non-curable in most patients. Thus, novel therapeutic approaches are still needed to enhance treatment outcomes and limit or delay the use of potentially more toxic therapies.

About EO2463:

EO2463 is an innovative, off-the-shelf immunotherapy candidate that combines four synthetic OncoMimic peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the B lymphocyte-specific lineage markers CD20, CD22, CD37, and CD268 (BAFF receptor). EO2463 also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2). The unique ability of EO2463 immunotherapy to selectively target multiple B cell markers enables the destruction of malignant B lymphocytes that are abundant in NHL. By ensuring broad target coverage across malignant B cells while avoiding a detrimental impact on normal peripheral B cells, this novel approach aims to simultaneously improve safety and maximize efficacy, reducing the tumor cells’ capacity to develop immune escape mechanisms.

On May 24, 2024 Renovaro Inc. (NASDAQ: RENB) and the Amsterdam UMC Cancer Center reported an intended partnership and therefore signed an MoU to establish a joint company based in the Netherlands aimed at pioneering the next generation of personalized cancer immunotherapy (Press release, Amsterdam UMC, MAY 24, 2024, View Source [SID1234643671]). Both Renovaro and Amsterdam UMC emphasize the need to carry out the appropriate corporate and scientific due diligence before taking these next steps. Alongside the independent validation any final contractual commitments are subject to approval from both executive boards.

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This collaboration would bring together Renovaro’s proprietary cancer vaccine technology and the Cancer Center’s expertise in several ancillary immunomodulatory technologies, towards innovative advancements in cancer treatment.

The proposed "Newco" will be headquartered in Amsterdam, The Netherlands. By merging Renovaro’s cutting-edge vaccine technology with the Cancer Center’s expertise, the aim is to develop personalized cancer immunotherapy solutions tailored to individual patients, overcoming immunotherapy resistance.

"We believe that by combining our expertise in cancer research and therapy with Renovaro’s innovative allogenic dendritic vaccine technology, we can accelerate the development of personalized cancer treatments," said Prof. Geert Kazemier, Director of the Amsterdam UMC Cancer Center. "This once again represents our commitment to advancing cancer immunotherapy and improving patient outcomes."

"We are thrilled to partner with the Amsterdam UMC Cancer Center to drive innovation in cancer immunotherapy," said Coenraad K. van Kalken MD PhD, Director of RenovaroCube. "This collaboration represents a recognition of our potentially transformative technologies and a strategic alignment of our shared vision to change cancer treatment through personalized medicine. Also, as part of the MoU certain clinical activities would be moved to Amsterdam."

This new venture will operate independently, with a dedicated team of researchers collaborating closely with experts from both RenovaroBio and the Amsterdam UMC Cancer Center and will benefit from the combined resources, expertise, and extensive networks of its parent organizations, ensuring a strong foundation for success.

Both Renovaro and the Amsterdam UMC Cancer Center believe that the commitment to driving innovation in more non-invasive cancer therapies will enable significant strides in the fight against cancer, offering hope to patients worldwide.

On May 24, 2024 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, reported that an abstract including new data from the single-arm pilot phase of the investigator-initiated, randomized CheMo4METPANC Phase 2 combination clinical trial was accepted for presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 31-June 4, 2024 in Chicago, Illinois (Press release, BioLineRx, MAY 24, 2024, View Source [SID1234643670]). The CheMo4METPANC trial is evaluating the company’s CXCR4 inhibitor motixafortide, the PD-1 inhibitor cemiplimab, and standard-of-care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone, in first-line pancreatic cancer (PDAC).

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Updated results of the pilot study portion of the Phase 2 study include a new analysis of paired pre- and on-treatment biopsy samples that demonstrated an increase in CD8+ T-cell density in tumors from all 11 patients treated with the combination of motixafortide, cemiplimab and standard-of-care chemotherapies gemcitabine and nab-paclitaxel (P = 0.007). As of February 6, 2024, 7 patients achieved partial response (64%), including 6 confirmed partial responses, and 10 patients (91%) had disease control compared to historic partial response and disease control rates of 23% and 48%, respectively, with gemcitabine and nab-paclitaxel. Preliminary median progression-free survival (PFS) was 9.6 months compared to historic median PFS of 5.5 months with gemcitabine and nab-paclitaxel.

"We continue to be encouraged by the data from the pilot phase of this ongoing Phase 2 study, including the initial efficacy results, as well as new findings that the combination therapy including motixafortide demonstrated increased CD8+ T-cell density in the tumors of all patients treated," said Philip Serlin, Chief Executive Officer of BioLineRx Ltd. "The biopsy sample findings continue to confirm immune cell activation and tumor microenvironment modulation observed in previous clinical evaluation. We look forward to our continued collaboration with Columbia University on this clinical research, and to advancing a potential new therapeutic option for pancreatic cancer, which is urgently needed for this difficult-to-treat disease."

Based on the encouraging results from the pilot phase of the study, the CheMo4METPANC Phase 2 trial was amended to become a randomized study, with planned enrollment increasing from 30 to 108 patients. Sponsored by Columbia University, the trial is the first large, multi-center, randomized study evaluating motixafortide with a PD-1 inhibitor and first-line PDAC chemotherapies.

Poster Presentation at ASCO (Free ASCO Whitepaper) 2024
McCormick Place, Chicago, Illinois

Poster Session Details

Primary Track: Gastrointestinal Cancer—Gastroesophageal, Pancreatic and Hepatobiliary
Title: CheMo4METPANC: A randomized phase 2 study with combination chemotherapy (gemcitabine and nab-paclitaxel), chemokine (C-X-C) motif receptor 4 inhibitor (motixafortide), and immune checkpoint blockade (cemiplimab) compared to chemotherapy alone in metastatic treatment-naïve pancreatic adenocarcinoma
Presenter: Gulam Abbas Manji, MD, PhD, Columbia University Herbert Irving Comprehensive Cancer Center
Abstract: TPS4208 (see abstract)
Poster # 174a
Date: Saturday, June 1, 2024
Time: 1:30 PM CDT
Location: Hall A

About CheMo4METPANC Phase 2 Clinical Trial
The multi-center CheMo4METPANC Phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT04543071) is a randomized, investigator-initiated clinical trial in first line metastatic pancreatic cancer. Sponsored by Columbia University, and supported equally by BioLineRx and Regeneron, the study is evaluating the combination of CXCR4 inhibitor motixafortide, PD-1 inhibitor cemiplimab, and standard of care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone, in 108 patients. The trial’s primary endpoint is progression free survival (PFS). Secondary objectives include safety, response rate, disease control rate, duration of clinical benefit and overall survival.

About Pancreatic Cancer
Pancreatic cancer has a low rate of early diagnosis and a poor prognosis. In the United States in 2024, an estimated 66,000 adults will be diagnosed with the disease, which accounts for approximately 3% of all cancers in the U.S. and about 7% of all cancer deaths.1 Worldwide, an estimated 496,000 people were diagnosed with the disease in 2020. In the U.S., if the cancer is detected at an early stage when surgical removal of the tumor is possible, the 5-year relative survival rate is 44%. About 12% of people are initially diagnosed at this stage. If the cancer has spread to surrounding tissues or organs, the 5-year relative survival rate is 15%. For the 52% of patients who are initially diagnosed with metastatic cancer, the 5-year relative survival rate is 3%.2 In particular, hepatic (liver) metastases are a critical risk factor driving poor prognoses for patients with metastatic PDAC. These data highlight the need for the development of new therapeutic options.

About Motixafortide in Cancer Immunotherapy
Motixafortide inhibits CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including pancreatic ductal adenocarcinoma (PDAC). Motixafortide leverages the expression of the CXCR4 receptor on different immune cells and potentiates the immune system against the tumor. Among CXCR4-expressing immune cells, some exhibit anti-tumoral activity, such as effector T cells and some exhibit pro-tumoral activity and support tumor growth. By blocking the CXCR4 receptor, motixafortide was shown in a Phase 2 study in pancreatic cancer patients to enhance anti-tumoral activity and to ameliorate the pro-tumoral activities by modulating the effector/suppressor cell ratio towards a proinflammatory profile.

On May 24, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported the presentation of new analyses for BRUKINSA (zanubrutinib) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, May 31 – June 4, 2024 (Press release, BeiGene, MAY 24, 2024, View Source [SID1234643669]). The presentations highlight analyses of the efficacy and safety of BRUKINSA compared to other Bruton’s tyrosine kinase inhibitors (BTKis) used to treat chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

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"At this year’s ASCO (Free ASCO Whitepaper), multiple presentations continue to add to our extensive body of evidence demonstrating BRUKINSA’s uniquely differentiated clinical profile," Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. "These new analyses, which highlight improved PFS and response rates and a low usage of antihypertensive medicines, provide valuable insights for oncologists to consider when making treatment decisions for their patients with CLL and SLL."

BRUKINSA Survival and Response Rates for CLL vs. Acalabrutinib and other BTKis in a Network Meta-Analysis

A network meta-analysis evaluated the relative efficacy of available treatments for patients with high-risk relapsed/refractory (R/R) CLL using data from three randomized controlled clinical trials: ALPINE, ELEVATE-RR and ASCEND. The analysis found a statistically significant improvement in PFS for BRUKINSA over acalabrutinib in high-risk patients and a trend toward improvement in overall survival (OS), overall response (ORR) and complete response (CR). BRUKINSA led to statistically significant improvements in PFS, as well as a trend toward improvement in OS, vs. ibrutinib and bendamustine + rituximab/idelalisib + rituximab (BR/IR).

"Given the lack of head-to-head trials comparing BTK inhibitors in high-risk R/R CLL patients, we undertook a network meta-analysis to estimate the relative efficacy of available treatments," said Mazyar Shadman, M.D. M.P.H, Associate Professor and Innovators Network Endowed Chair, Assistant Medical Director, Cellular Immunotherapy, Fred Hutch Cancer Center and University of Washington. "We found zanubrutinib to be the most efficacious BTKi for patients with high-risk R/R CLL, offering significantly delayed disease progression and favorable response compared with the other BTKi treatments in the analysis, including acalabrutinib."

Network meta-analyses are intended to be hypothesis-generating, and do not establish superior efficacy or safety of one drug over another. Results should be viewed in the context of analysis limitations and available randomized clinical trial data.

This poster will be presented Monday, June 3, from 9 a.m. – noon CT (Abstract #7048).
BRUKINSA Effective and Generally Well-Tolerated for Patients with CLL/SLL Regardless of Prior Ibrutinib Use

A retrospective analysis assessed treatment patterns, treatment-emergent adverse events (TEAEs), treatment-limiting adverse events (TLAEs) and treatment-related mortality among patients with CLL/SLL treated at Kaiser Permanente Northern California. Among 281 patients who received BRUKINSA, 190 switched from ibrutinib and 91 received only BRUKINSA, with a median follow up of 24.4 and 8.2 months, respectively. Similar TEAE rates were seen with both BTKi therapies, with lower TLAE rates with BRUKINSA. Cardiac TLAE and non-TLAE rates overall were higher with ibrutinib than BRUKINSA, and the rates decreased after switching to BRUKINSA. There were no reports of treatment-related deaths.

This poster will be presented Monday, June 3, from 9 a.m. – noon CT (Abstract #11158).
ALPINE Post Hoc Analysis Shows Less Frequent Initiation of Anti-hypertensive Medications in Patients Treated with BRUKINSA vs. Ibrutinib

A post-hoc analysis of the ALPINE clinical trial data evaluated the risk of developing hypertension based on initiation of anti-hypertensive medications among patients with CLL/SLL treated with BRUKINSA vs. ibrutinib. The analysis found that initiation of new anti-hypertensives or a new class of anti-hypertensives occurred less frequently in the BRUKINSA arm vs. the ibrutinib arm. In addition, initiation of anti-hypertensives occurred sooner for patients treated with ibrutinib vs. BRUKINSA. Data from this analysis provide important insights when evaluating the overall safety profile of individual BTKi treatments.

This abstract is available online (Abstract #e19016).
During the meeting, BeiGene will also sponsor a virtual panel discussion featuring perspectives from leading hematology/oncology experts as they discuss the BTKi treatment evolution, and the considerations healthcare providers and patients should weigh when choosing treatment for CLL. The panel, titled "Exploring the landscape of next-generation BTK inhibitors in blood cancers" will take place during the Endpoints at #ASCO24 event on June 4 at 12:35 – 1:05 p.m. ET (register here).

For additional information about BeiGene’s presence at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, please visit our meeting hub in our newsroom.

About BRUKINSA (zanubrutinib)
BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

U.S. Indications and Important Safety Information for BRUKINSA (zanubrutinib)

INDICATIONS
BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Waldenström’s macroglobulinemia (WM).
Mantle cell lymphoma (MCL) who have received at least one prior therapy.
Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.
Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy.
The MCL, MZL and FL indications are approved under accelerated approval based on overall response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients.

Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients.

Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA (N=1729) are decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Please see full U.S. Prescribing Information including U.S. Patient Information.