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.

On May 24, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that new and updated data from several studies of compounds discovered by HUTCHMED will be presented at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting, taking place May 31 – June 4, 2024 in Chicago, IL and online (Press release, Hutchison China MediTech, MAY 24, 2024, View Source [SID1234643602]).

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Results will be presented from the registration Phase II study of fruquintinib combined with sintilimab in 98 second-line or above patients with endometrial cancer ("EMC") with pMMR status by central laboratory analysis, which supported the New Drug Application (NDA) filed in China. The primary endpoint was objective response rate ("ORR") per RECIST v1.1, assessed by an independent review committee. The combination showed meaningful efficacy improvements in advanced EMC patients with pMMR status, regardless of prior bevacizumab treatment, with a manageable safety profile. The median follow-up time was 15.7 months. The ORR in 87 efficacy evaluable patients was 35.6% including two complete responses. Disease control rate ("DCR") was 88.5%, and duration of response was not reached, with 80.7% remaining in response after nine months. Amongst the 98 patients, median progression-free survival (PFS) was 9.5 months, and median overall survival (OS) was 21.3 months. Further details are available in the abstract link below.

Following the initial data of the FRUTIGA Phase III study of fruquintinib in second-line gastric cancer published during the February 2024 ASCO (Free ASCO Whitepaper) Plenary Series session, further updated efficacy data in key subgroups, and quality of life data will be presented at this year’s ASCO (Free ASCO Whitepaper) annual meeting. In addition, further data from the FRESCO and FRESCO-2 Phase III colorectal cancer studies, the study of surufatinib combinations in small cell lung cancer, and initial clinical data for the ERK1/2 inhibitor HMPL-295 will be presented.

Details of the presentations, including links to available abstracts, are as follows:

Abstract title Presenter / Lead author Presentation details

SPONSORED STUDIES
Fruquintinib plus Sintilimab in Treated Advanced Endometrial Cancer (EMC) Patients (Pts) with pMMR Status: Results From a Multicenter, Single‑Arm Phase 2 Study Xiaohua Wu, Fudan University Shanghai Cancer Center, Shanghai, China #5619
Poster Session – Gynecologic Cancer
Efficacy and safety of fruquintinib in patients with metastatic colorectal cancer according to prior treatment sequence in the refractory setting: Results from FRESCO and FRESCO-2 Tanios S. Bekaii-Saab,
Mayo Clinic, U.S. #3579
Poster Session – Gastrointestinal Cancer — Colorectal and Anal
Fruquintinib in Refractory Metastatic Colorectal Cancer
Cathy Eng,
Vanderbilt-Ingram Cancer Center, U.S. Link
Education Session: New Drugs in Oncology: Incorporation Into Practice
Updates on Abstract 438730: Fruquintinib Plus Paclitaxel Versus Paclitaxel as Second-Line Therapy for Patients with Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (FRUTIGA): A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 3 Study Feng Wang, Sun Yat-Sen University Cancer Center, Guangzhou, China Link
Education Session: ASCO (Free ASCO Whitepaper) Plenary Series: Rapid Abstract Updates
Surufatinib plus PD-1/L1 inhibitors as maintenance therapy following first line (1L) platinum-based chemotherapy combined with PD-1/L1 inhibitors in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) Yi Hu, Chinese PLA General Hospital, Beijing, China #e15109
Publication Only: Developmental Therapeutics — Molecularly Targeted Agents and Tumor Biology
First-in-human study of HMPL-295, an ERK1/2 inhibitor, in patients with advanced solid tumors: dose-escalation results of monotherapy Xianjun Yu, Fudan University Shanghai Cancer Center, Shanghai, China #e15112
Publication Only: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

INVESTIGATOR-INITIATED STUDIES
Stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer: updated findings from a single-arm, prospective phase II trial (RIFLE) Chen Yajie, Zhang Zhen, Fudan University Shanghai Cancer Center, Shanghai, China #e15570
Publication Only: Gastrointestinal Cancer—Colorectal and Anal
A propensity score matched comparison of fruquintinib (FRU) versus FRU combined with PD-1 inhibitors for microsatellite stability (MSS) metastatic colorectal cancer: real-world data Lina He, Shuiping Tu,
Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China #e15564
Publication Only: Gastrointestinal Cancer—Colorectal and Anal
Phase Ib/II trial of hepatic arterial infusion chemotherapy (HAIC) in combination with fruquintinib as third-line therapy for refractory unresectable colorectal cancer liver metastases Zhu Xu,
Peking University Cancer Hospital and Institute, Beijing, China #3561
Poster Session – Gastrointestinal Cancer—Colorectal and Anal
Efficacy and safety of fruquintinib plus trifluridine/tipiracil (TAS-102) as third-line treatment in patients with metastatic colorectal adenocarcinoma: Results from a single arm, phase 2, multicenter study Jianjun Peng,
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China #3536
Poster Session – Gastrointestinal Cancer — Colorectal and Anal
A phase II study to evaluate the efficacy and safety of fruquintinib combined with tislelizumab and Hepatic arteryinfusion chemotherapy (HAIC) for advanced colorectal cancer liver metastases: An updated analysis of survival Lu Wang, Zhang Ti,
Fudan University Shanghai Cancer Center, Shanghai, China #3543
Poster Session – Gastrointestinal Cancer — Colorectal and Anal
Fruquintinib combined with sintilimab and SOX as conversion therapy for unresectable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): A single-arm, open-label, phase 2 clinical trial Suxia Luo, Fei Ma,
Henan Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China #e16021
Publication Only: Gastrointestinal Cancer — Gastroesophageal, Pancreatic, and Hepatobiliary
Short-course radiotherapy (SCRT) followed by fruquintinib plus adebrelimab and CAPOX in the total neoadjuvant therapy of locally advanced rectal cancer (LARC): a multicenter, single-arm, open-label, phase II study Tao Zhang, Zhenyu Lin,
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China TPS3643
Poster Session: Gastrointestinal Cancer — Colorectal and Anal
Fruquintinib plus capecitabine versus capecitabine as first-line maintenance treatment of metastatic colorectal cancer (mCRC): Update results from the randomized, controlled, phase Ib/II study Junjie Peng, Wenhua Li,
Fudan University Shanghai Cancer Center, Shanghai, China #3567
Poster Session: Gastrointestinal Cancer — Colorectal and Anal
Efficacy and safety of fruquintinib plus investigator’s choice of chemotherapy as second-line therapy in metastatic colorectal cancer: updated results of a multicenter, single-arm, phase 2 trial Yongshun Chen, Wensi Zhao,
Renmin Hospital of Wuhan University, Wuhan, China #3571
Poster Session: Gastrointestinal Cancer — Colorectal and Anal
Comparative analysis of first-line therapy with fruquintinib plus chemotherapy versus standard therapy in advanced metastatic colorectal cancer (mCRC): A prospective cohort study compared with propensity score matching (PSM) cohort Fuxiang Zhou, Wenbo Wang,
Zhongnan Hospital of Wuhan University, Wuhan, China #3591
Poster Session: Gastrointestinal Cancer —Colorectal and Anal
Efficacy and safety of fruquintinib-based treatment in patients with refractory bone and soft tissue sarcomas after developing resistance to several TKIs: A multi-centered retrospective study Lu Xie, Binghao Li,
Peking University People’s Hospital, Beijing, China; The Second Affiliated Hospital Zhejiang University, Hangzhou, China #11528
Poster Session: Sarcoma
Disitamab vedotin combined with fruquintinib in patients with HER2-expressing or HER2 mutation/amplified metastatic colorectal cancer refractory to at least two standard regimens: A prospective, exploratory, single-arm study Hui Xu,
Zhongnan Hospital of Wuhan University. Wuhan, China #e15003
Publication Only: Developmental Therapeutics — Molecularly Targeted Agents and Tumor Biology
Surufatinib combined with TAS-102 in third- or later-line therapy of patients with metastatic pancreatic cancer (mPDAC): an open-Label, single-Arm, phase II Study Dongsheng Zhang,
Sun Yat-sen University Cancer Center, Guangzhou, China #e16297
Publication Only: Gastrointestinal Cancer — Gastroesophageal, Pancreatic, and Hepatobiliary
Surufatinib monotherapy or combined with vinorelbine as a late-line therapy in patients with refractory advanced non–small cell lung cancer (NSCLC) Yanfang Zheng,
Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China #e20543
Publication Only: Lung Cancer — Non-Small Cell Metastatic
Updated efficacy and safety results from the phase Ib/II study of surufatinib combined with camrelizumab and chemotherapy in patients with advanced colorectal cancer Liangjun Zhu, Sheng Li,
Jiangsu Cancer Hospital, Nanjing, China #e15547
Publication Only: Gastrointestinal Cancer — Colorectal and Anal
Phase II study to evaluate surufatinib in patients with osteosarcoma and soft tissue sarcoma who have failed in standard chemotherapy: updated analysis Xing Zhang,
Sun Yat-sen University Cancer Center, Guangzhou, China #11539
Poster Session: Sarcoma
Efficacy and safety of Surufatinib combined with EP regimen and Serplulimab in first-line treatment of NEC Tao Zhang, Zhenyu Lin,
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China #e15123
Publication Only: Developmental Therapeutics — Molecularly Targeted Agents and Tumor Biology
Performance of surufatinib in treating advanced neuroendocrine neoplasms: Insights from a real-world study Qing Zhai, Linhui Zhu,
Fudan University Shanghai Cancer Center; Shanghai Medical College, Fudan University, Shanghai, China #e15124
Publication Only: Developmental Therapeutics — Molecularly Targeted Agents and Tumor Biology
Epidemiological investigation of neuroendocrine differentiation in carcinomas: Focus on pancreatic and cholangiocarcinoma cohorts Susheng Shi, Yaru Wen,
Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China #e16375
Publication Only: Gastrointestinal Cancer — Gastroesophageal, Pancreatic, and Hepatobiliary
Efficacy and safety of surufatinib, toripalimab, nab-paclitaxel in combination with radiotherapy or surgery in the first-line treatment of esophageal squamous cell cancer: A single-centered prospective clinical trial Fang Liu, Xiang Huang,
Chinese PLA General Hospital, Beijing, China #e16047
Publication Only: Gastrointestinal Cancer — Gastroesophageal, Pancreatic, and Hepatobiliary
Efficacy and safety of second-line treatment with surufatinib for anlotinib-resistant radioiodine-refractory differentiated thyroid cancer: An exploratory multicenter study Libo Chen, Yang Wang,
Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China #e15127
Publication Only: Developmental Therapeutics — Molecularly Targeted Agents and Tumor Biology