On November 5, 2024 Genmab A/S (Nasdaq: GMAB) reported more than 20 abstracts evaluating epcoritamab-bysp (EPKINLY), a T-cell engaging bispecific antibody administered subcutaneously, across lines of therapy and B-cell non-Hodgkin’s lymphoma (NHL) subtypes, will be presented at the 66th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), being held at the San Diego Convention Center in San Diego, California, and online, December 7-10 (Press release, Genmab, NOV 5, 2024, View Source [SID1234647761]).

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The breadth of the epcoritamab development program will be featured at this year’s ASH (Free ASH Whitepaper) in four oral presentations. Three of the oral presentations will highlight data evaluating fixed-duration subcutaneous epcoritamab in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), and relapsed/refractory (R/R) follicular lymphoma (FL). The fourth oral presentation will feature the results of a study evaluating epcoritamab monotherapy in patients with R/R chronic lymphocytic leukemia (CLL). Additionally, three-year efficacy and safety data for subcutaneous epcoritamab in patients with R/R DLBCL from the EPCORE NHL-1 trial will be presented.

"The data evaluating epcoritamab being presented at this year’s ASH (Free ASH Whitepaper) highlight the encouraging clinical results we have seen across epcoritamab clinical trials and demonstrate its potential as a core therapy for B-cell malignancies," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. "This has been a pivotal year for epcoritamab, and alongside our partner AbbVie, we are committed to progressing the comprehensive epcoritamab development program with the goal of potentially providing additional therapeutic options to patients in need of treatments."

All abstracts accepted for presentation have been published on the ASH (Free ASH Whitepaper) Website.

2024 R&D Update and ASH (Free ASH Whitepaper) Data Review

On Wednesday, December 11, at 11:00 AM EST (5:00 PM CET/4:00 PM GMT), Genmab will host its 2024 R&D Update and ASH (Free ASH Whitepaper) Data Review. The event will be virtual and webcast live. Details, including the webcast link and registration will be available on www.genmab.com. This meeting is not an official program of the ASH (Free ASH Whitepaper) Annual Meeting.

Abstracts accepted for presentation at ASH (Free ASH Whitepaper) include:

Oral Presentations

Abstract Number

Abstract Title

Type of Presentation

Date/Time of Presentation

342

Fixed-Duration Epcoritamab + R2 Drives Deep and Durable Responses in Patients with Relapsed or Refractory Follicular Lymphoma: 2-Year Follow-Up from Arm 2 of the EPCORE NHL-2 Trial

Oral

Saturday, December 7, 4:00 – 5:30 PM PT

581

Fixed-Duration Epcoritamab + R-CHOP Induces High Complete Response Rates in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma with High-Risk Features: Long-Term Results from the EPCORE NHL-2 Trial

Oral

Sunday, December 8, 12:00 – 1:30 PM PT

867

EPCORE DLBCL-3 First Disclosure: Fixed-Duration Epcoritamab Monotherapy in Older (≥75 y), Anthracycline-Ineligible Patients with Previously Untreated Large B-Cell Lymphoma

Oral

Monday, December 9, 2:45 – 4:15 PM PT

883

Epcoritamab Monotherapy in Patients (Pts) with Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Results from CLL Expansion and Optimization Cohorts of EPCORE CLL-1

Oral

Monday, December 9, 2:45 – 4:15 PM PT

Poster Presentations

Abstract Number

Abstract Title

Type of Presentation

Date/Time of Presentation

1414

Exposure-Response Analyses Supporting Optimal Epcoritamab 48 mg Full Dose and Dosing Schedule in Relapsed or Refractory Follicular Lymphoma

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

1622

Epcoritamab with R-CHOP Overcomes Poor Risk Features of High Metabolic Tumor Volume in High-Risk Large B-Cell Lymphoma

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

1627

Fixed-Duration Epcoritamab in Combination with Bendamustine + Rituximab for First-Line Treatment of Follicular Lymphoma: Initial Results from EPCORE NHL-2 Arm 3

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

1703

Trends in All-Cause Mortality Rates in Patients with Follicular Lymphoma in the US before and during the COVID-19 Pandemic: A Retrospective Observational Study

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

1734

Immune Biomarkers of Mechanism of Action of Epcoritamab (Epcor) Plus Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) in Frontline DLBCL

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

1737

Efficacy and Safety of Epcoritamab Monotherapy in Patients with Relapsed or Refractory LBCL Not Previously Exposed to CAR T: Subanalysis of the EPCORE NHL-1 Trial

Poster

Saturday December 7, 5:30 – 7:30 PM PT

2349

Indirect Comparisons of the Efficacy of Epcoritamab Vs Glofitamab in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

2998

Epcoritamab Induces in vitro-derived Terminally Differentiated Exhausted T Cells to Kill B Cells

Poster

Saturday, December 7, 5:30 – 7:30 PM PT

3106

Fixed-Duration Epcoritamab + R-Mini-CHOP in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma Ineligible for Full-Dose R-CHOP: Updated Results from Arm 8 of the EPCORE NHL-2 Trial

Poster

Sunday, December 8, 6:00 – 8:00 PM PT

3110

Fixed-Duration Epcoritamab Plus Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Updated Results from Arm 1 of the Epcore NHL-5 Trial

Poster

Sunday, December 8, 6:00 – 8:00 PM PT

3115

Prior Bendamustine (Benda) Exposure Did Not Impact Clinical Outcomes and Decreased CD4+ but Not CD8+ T-Cells in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with the Bispecific Antibody Epcoritamab (Epcor)

Poster

Sunday, December 8, 6:00 – 8:00 PM PT

3231

T cells from CLL patients on venetoclax mount potent cytotoxic responses in combination with epcoritamab, a CD20/CD3 bispecific antibody.

Poster

Sunday, December 8, 6:00 – 8:00 PM PT

3723

Patient Characteristics and Treatment Patterns for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) By CAR T Eligibility and Treatment Status in France, Germany, Italy, Spain, the UK, and Japan

Poster

Sunday, December 8, 6:00 – 8:00 PM PT

4480

3-Year Update from the EPCORE NHL-1 Trial: Epcoritamab Leads to Deep and Durable Responses in Relapsed or Refractory Large B-Cell Lymphoma

Poster

Monday, December 9, 6:00 – 8:00 PM PT

4491

Three-Factor Prediction Model for Grade 2+Cytokine Release Syndrome in Large B-Cell Lymphoma Patients Receiving Epcoritamab Monotherapy

Poster

Monday, December 9, 6:00 – 8:00 PM PT

5124

Epcoritamab for Relapsed/ Refractory B cell Lymphoma – the Israeli Real-World Experience

Poster

Monday, December 9, 6:00 – 8:00 PM PT

E-publications

Abstract Number

Abstract Title

Type of Presentation

Date/Time of Presentation

7614

Cost-Effectiveness of Epcoritamab Versus Glofitamab in Relapsed or Refractory Large B-Cell Lymphoma after at Least Two Lines of Therapy in the United States

E-publication

N/A

7617

A Canadian Cost-Utility Analysis of Epcoritamab Versus Current Therapies in Third-Line or Later Large B-Cell Lymphoma

E-publication

N/A

7757

Epcoritamab plus Gemcitabine and Oxaliplatin versus Glofitamab or Rituximab plus Gemcitabine and Oxaliplatin in Transplant-Ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients: A Match-Adjusted Comparative Analysis

E-publication

N/A

7760

Epcoritamab plus Gemcitabine and Oxaliplatin versus Rituximab, Gemcitabine, and Oxaliplatin in Transplant-Ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients: A Match-Adjusted Comparative Analysis

E-publication

N/A

7802

Matching-Adjusted Indirect Treatment Comparison of Epcoritamab versus Zanubrutinib Plus Obinutuzumab in Relapsed or Refractory Follicular Lymphoma

E-publication

N/A

The safety and efficacy of epcoritamab has not been established for these investigational uses.

About Epcoritamab

Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.i

Epcoritamab (approved under the brand name EPKINLY in the U.S. and Japan, and TEPKINLY in the EU) has received regulatory approval in certain lymphoma indications in several territories. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational R/R FL indication and additional approvals for the R/R DLBCL indication.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes four ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice chemotherapy (NCT04628494), a trial evaluating epcoritamab in combination with R-CHOP in adult participants with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL (NCT05409066), and a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information.

EPKINLY (epcoritamab-bysp) U.S. IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

Cytokine release syndrome (CRS), which is common during treatment with EPKINLY and can be serious or life-threatening. To help reduce your risk of CRS, you will receive EPKINLY on a step-up dosing schedule (when you receive 2 or 3 smaller step-up doses of EPKINLY before your first full dose during your first cycle of treatment), and you may also receive other medicines before and for 3 days after receiving EPKINLY. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule.
Neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY.
People with DLBCL or high-grade B-cell lymphoma should be hospitalized for 24 hours after receiving their first full dose of EPKINLY on day 15 of cycle 1 due to the risk of CRS and neurologic problems.

Tell your healthcare provider or get medical help right away if you develop a fever of 100.4°F (38°C) or higher; dizziness or lightheadedness; trouble breathing; chills; fast heartbeat; feeling anxious; headache; confusion; shaking (tremors); problems with balance and movement, such as trouble walking; trouble speaking or writing; confusion and disorientation; drowsiness, tiredness or lack of energy; muscle weakness; seizures; or memory loss. These may be symptoms of CRS or neurologic problems. If you have any symptoms that impair consciousness, do not drive or use heavy machinery or do other dangerous activities until your symptoms go away.

EPKINLY can cause other serious side effects, including:

Infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment and treat you as needed if you develop an infection. You should receive medicines from your healthcare provider before you start treatment to help prevent infection. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
Low blood cell counts, which can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cells (neutropenia), which can increase your risk for infection; low red blood cells (anemia), which can cause tiredness and shortness of breath; and low platelets (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider will monitor you for symptoms of CRS, neurologic problems, infections, and low blood cell counts during treatment with EPKINLY. Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all your medical conditions, including if you have an infection, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. If you receive EPKINLY while pregnant, it may harm your unborn baby. If you are a female who can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with EPKINLY and you should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.

In DLBCL or high-grade B-cell lymphoma, the most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea. The most common severe abnormal laboratory test results include decreased white blood cells, decreased red blood cells, and decreased platelets.

In follicular lymphoma the most common side effects of EPKINLY include injection site reactions, CRS, COVID-19, tiredness, upper respiratory tract infections, muscle and bone pain, rash, diarrhea, fever, cough, and headache. The most common severe abnormal laboratory test results include decreased white blood cells and decreased red blood cells.

These are not all of the possible side effects of EPKINLY. Call your doctor for medical advice about side effects. You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see Medication Guide, including Important Warnings.

On November 5, 2024 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported the upcoming presentation of new pre-clinical data on its anti-GPC3 in vivo chimeric antigen receptor macrophage and monocyte (together, "CAR-M") therapy for the treatment of hepatocellular carcinoma ("HCC"), developed in collaboration with Moderna, Inc. (Nasdaq: MRNA) (Press release, Carisma Therapeutics, NOV 5, 2024, View Source [SID1234647760]). The data will be presented in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) ("SITC") Annual Meeting in Houston, Texas, on November 8, 2024.

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The abstract, titled "Pre-Clinical Efficacy of a Novel Anti-GPC3 In Vivo CAR-M for Hepatocellular Carcinoma," presents the first pre-clinical data on the development candidate targeting Glypican-3 ("GPC3"), a tumor-associated antigen commonly expressed in HCC. This novel off-the-shelf approach reprograms endogenous myeloid cells in vivo using lipid nanoparticles ("LNP") to deliver mRNA encoding CARs. The data show that this in vivo CAR-M therapy has significant potential as a treatment for GPC3+ solid tumors, including HCC.

"Our data at SITC (Free SITC Whitepaper) this year highlights the groundbreaking potential of the in vivo CAR-M platform," said Steven Kelly, President and Chief Executive Officer of Carisma. "The pre-clinical results demonstrate robust anti-tumor activity and pave the way for an off-the-shelf therapy for hard-to-treat cancers like hepatocellular carcinoma. This data underscores the progress we’ve made, and we’re eager to advance this promising therapy into clinical development."

SITC Presentations Details:

Title: Pre-clinical efficacy of a novel anti-GPC3 in vivo CAR-M for hepatocellular carcinoma
Publication Number: 329
Session Date & Time: Friday, Nov. 8, 2024
Location: Exhibit Halls A B George R. Brown Convention Center

Title: A Phase 1, First-in-Human study of autologous monocytes engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2 overexpressing solid tumors
Publication Number: 659
Session Date & Time: Friday, Nov. 8, 2024
Location: Exhibit Halls A B George R. Brown Convention Center

The poster presented at SITC (Free SITC Whitepaper) 2024 will be available online in the "Publications" section of Carisma’s website at View Source following the start of the poster session.

On November 5, 2024 Bexion Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing a novel class of biologic therapy to treat solid tumor cancers and chemotherapy-induced peripheral neuropathy (CIPN), reported the Company will participate in the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting taking place November 6 – 11, 2024, in Houston, TX. Poster presentation details are included below (Press release, Bexion, NOV 5, 2024, View Source [SID1234647759]).

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Poster Presentation Details:

Title: BXQ-350: A novel approach to rebalancing the tumor’s immune response
Abstract Number: 1331
Date: Friday, November 8, 2024
Author: Gilles Tapolsky, PhD, Vice President of Pharmacology, Bexion Pharmaceuticals

The titles of the abstracts are currently available on the SITC (Free SITC Whitepaper) 2024 Abstracts webpage. All posters will be available on the virtual meeting platform beginning November 7, 2024, at 9 AM ET.

About SITC (Free SITC Whitepaper)
The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) is the world’s leading member-driven organization specifically dedicated to improving cancer patient outcomes by advancing the science and application of cancer immunotherapy. Currently, SITC (Free SITC Whitepaper) has more than 4,500 members who represent over 35 medical specialties in 63 countries around the world. Through emphasis on high-caliber scientific meetings; dedication to education and outreach activities; focus on initiatives of major importance in the field; and commitment to collaborations with like-minded domestic and international organizations, government and regulatory agencies, associations and patient advocacy groups, SITC (Free SITC Whitepaper) brings together all aspects of the cancer immunology and immunotherapy community.

About BXQ-350
Bexion’s lead drug candidate is BXQ-350, a first-in-class biologic containing the multifunctional, sphingolipid activator protein, Saposin C, and a phospholipid. Multiple Phase 1 clinical trials in adult and pediatric patients have demonstrated a robust safety profile for BXQ-350 with evidence of single agent activity across multiple solid tumor types. Additionally, other clinical and non-clinical data suggest BXQ-350 has activity in chemotherapy-induced peripheral neuropathy, an area of high unmet medical need in patients treated with oxaliplatin and other chemotoxic agents.

On November 5, 2024 Eli Lilly and Company (NYSE: LLY) reported that data from studies of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, will be presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place Dec. 7-10 in San Diego (Press release, Eli Lilly, NOV 5, 2024, View Source [SID1234647758]).

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In an oral presentation, Lilly will report results from the Phase 3 BRUIN CLL-321 study, which is evaluating pirtobrutinib versus idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) in BTK inhibitor pretreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). BRUIN CLL-321, which previously met its primary endpoint, is the first randomized Phase 3 study to evaluate an exclusively BTK inhibitor pretreated CLL population. The submitted abstract utilized a February 2024 data cut-off date, and the presentation will utilize an August 2024 data cut-off date.

Additionally, Lilly will have poster presentations that share analyses of real-world data, including looking at overall survival associated with treatment sequences in patients with CLL/SLL, and pre-clinical data for a first-in-class B-cell activating factor receptor (BAFF)-RxCD3 bispecific antibody for the treatment of certain B-cell malignancies.

A full list of abstract titles and viewing details are listed below:

Jaypirca (pirtobrutinib)
Presentation Title: BRUIN CLL-321: Randomized Phase 3 Trial of Pirtobrutinib Versus Idelalisib Plus Rituximab (IdelaR) or Bendamustine Plus Rituximab (BR) in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Abstract Number: 886
Presentation Date & Time: Monday, Dec. 9, 3:30 p.m. PST
Location: Marriot Marquis San Diego Marina, Marriott Grand Ballroom 5-6
Presenter: Jeff P. Sharman

Presentation Title: Overall Survival Associated with Real-World Treatment Sequences in Patients with CLL/SLL in the United States
Abstract Number: 5114
Presentation Date & Time: Monday, Dec. 9, 6-8 p.m. PST
Location: San Diego Convention Center, Halls G-H
Presenter: Joanna Rhodes

Presentation Title: Continuity of Care for Patients with Chronic Lymphocytic Leukemia: An Analysis of Real-World Data
Abstract Number: 5033
Presentation Date & Time: Monday, Dec. 9, 6-8 p.m. PST
Location: San Diego Convention Center, Halls G-H
Presenter: Sameh Gaballa

LY4152199 (investigational BAFF-RxCD3 bispecific antibody)
Presentation Title: LY4152199, a First-in-Class BAFF-RxCD3 Bispecific Antibody for the Treatment of B-Cell Malignancies
Abstract Number: 2785
Presentation Date & Time: Sunday, Dec. 8, 6-8 p.m. PST
Location: San Diego Convention Center, Halls G-H
Presenter: Wei Yang

About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.

INDICATIONS FOR JAYPIRCA
Jaypirca is a kinase inhibitor indicated for the treatment of

Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. In a clinical trial, Grade ≥3 infections occurred in 24% of patients with hematologic malignancies, most commonly pneumonia (14%); fatal infections occurred (4.4%). Sepsis (6%) and febrile neutropenia (4%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor patients for signs and symptoms, evaluate promptly, and treat appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred in 3% of patients, including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (17%). Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (2.3%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor patients for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider benefit/risk of withholding Jaypirca 3-7 days pre- and post-surgery depending on type of surgery and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. In a clinical trial, Grade 3 or 4 cytopenias, including decreased neutrophils (26%), decreased platelets (12%), and decreased hemoglobin (12%), developed in Jaypirca-treated patients. Grade 4 decreased neutrophils (14%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients who received Jaypirca. In a clinical trial of patients with hematologic malignancies, atrial fibrillation or flutter were reported in 3.2% of Jaypirca-treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.5%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.5%). Patients with cardiac risk factors such as hypertension or previous arrhythmias may be at increased risk. Monitor for signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea) and manage appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients. The most frequent malignancy was non-melanoma skin cancer (4.6%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. Upon confirmation of DILI, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm in pregnant women. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of potential fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥20%) ARs in the BRUIN pooled safety population of patients with hematologic malignancies (n=593) were decreased neutrophil count (46%), decreased hemoglobin (39%), fatigue (32%), decreased lymphocyte count (31%), musculoskeletal pain (30%), decreased platelet count (29%), diarrhea (24%), COVID-19 (22%), bruising (21%), cough (20%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients. Serious ARs occurring in ≥2% of patients were pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%). Fatal ARs within 28 days of last Jaypirca dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations: ARs led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dosage modification in >5% of patients included pneumonia and neutropenia. ARs resulting in permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (29; 1.6), musculoskeletal pain (27; 3.9), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), pneumonia (16; 14), bruising (16; -).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥10% of Patients: hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), calcium decreased (19; 1.6), AST increased (17; 1.6), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), alkaline phosphatase increased (11; -), ALT increased (11; 1.6), potassium increased (11; 0.8). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Serious ARs occurred in 56% of patients. Serious ARs occurring in ≥5% of patients were pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%). Fatal ARs within 28 days of last Jaypirca dose occurred in 11% of patients, most commonly due to infections (10%), including sepsis (5%) and COVID-19 (2.7%).

Dose Modifications and Discontinuations: ARs led to dose reductions in 3.6%, treatment interruption in 42%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dose reductions in >1% included neutropenia; treatment interruptions in >5% of patients included pneumonia, neutropenia, febrile neutropenia, and COVID-19; permanent discontinuation in >1% of patients included second primary malignancy, COVID-19, and sepsis.

Most common ARs (≥20%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), dyspnea (22; 2.7), hemorrhage (22; 2.7), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥20% of Patients: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), platelet count decreased (30; 15), sodium decreased (30; -), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), lipase increased (21; 7), alkaline phosphatase increased (21; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use with Jaypirca increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid use of strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dosage according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use with Jaypirca decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid concomitant use of Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dosage according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Concomitant use with Jaypirca increased their plasma concentrations, which may increase risk of adverse reactions related to these substrates for drugs that are sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Special Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca and advise use of effective contraception during treatment and for one week after last dose. Presence of pirtobrutinib in human milk is unknown. Advise women not to breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Severe renal impairment increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to approved labeling.

On November 5, 2024 J INTS BIO reported a significant MOU signing ceremony at Baekyangnuri Plaza, Yonsei University, unveiling a groundbreaking AI-driven collaboration to revolutionize cancer treatment (Press release, J INTS BIO, NOV 5, 2024, View Source [SID1234647757]). This ambitious alliance unites leading institutions, including Yonsei University College of Medicine’s DAAN Cancer Research Institute, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Korea Research Institute of Chemical Technology (KRICT), and KAIST. The event featured a distinguished lineup, with Yuhan Corporation CEO Wook Je Cho, National Assembly Representative Seong Hoon Park, and KAIST’s Professor Joung Ho Kim, a prominent member of the National AI Committee, highlighting the extensive support from both government and industry sectors.

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Precision Medicine Redefined: AI Meets Multi-Omics

J INTS BIO is at the forefront of developing personalized lung cancer therapies through the integration of artificial intelligence and multi-omics technology. Multi-omics offers a comprehensive approach to disease biology by combining genomics, transcriptomics, metabolomics, and proteomics. Using AI and national supercomputing infrastructure, the project aims to enhance drug efficacy prediction and minimize toxicity, addressing the critical challenges that plague conventional oncology drug development.

Professor Byoung Chul Cho of Severance Hospital, a key figure behind the development of the highly successful lung cancer drug "Leclaza," emphasized, "AI is revolutionizing precision medicine. By employing AI and supercomputing, we can achieve ultra-precise analysis of patient tissue and genetic profiles, enabling the design of highly effective, personalized treatment strategies." KAIST’s Professor Joung Ho Kim added, "AI’s capacity to process immense biological datasets and apply machine learning for patient-specific predictions can drastically reduce clinical trial failure rates and accelerate the entire drug discovery process."

End-to-End Research Strategy: From Biopsies to AI-Optimized Therapies

The collaboration is structured around a comprehensive, four-phase research strategy: meticulous patient sample collection and preparation, AI-driven protein analysis using supercomputers, synthesis of drug candidates informed by AI insights, and rigorous clinical trials for validation.

The DAAN Cancer Research Institute at Yonsei University will lead the first phase, collecting lung cancer tissue and genomic samples and preparing them for AI model development. Using cell and animal models, the institute will validate AI predictions, identify drug resistance mechanisms, and refine algorithms to maximize accuracy.

DGIST’s Core Protein Resources Center will utilize national supercomputers to simulate protein-drug interactions, conducting high-precision structural analyses and virtual experiments. This work will confirm AI-driven hypotheses and facilitate the design of drugs tailored to the molecular characteristics of cancer.

KRICT’s Medicinal Bio Research Division will synthesize the AI-recommended drug candidates, subjecting them to thorough pharmacological and toxicological assessments. KRICT Director Kwang Rok Kim remarked, "AI is fundamentally transforming the landscape of drug discovery. It allows us to develop optimized therapeutic compounds faster and with greater safety, delivering unprecedented precision in medicine."

J INTS BIO will oversee the entire project, managing clinical trials to validate AI-based predictions and develop clinically proven, patient-specific treatment protocols. This approach aims to expedite the path from laboratory research to market readiness, making advanced cancer therapies more accessible to patients worldwide.

A Game-Changer in Oncology: Government and Industry in Harmony

This collaboration marks a transformative leap in cancer research, showcasing the potential of merging AI with biotechnology. Seong-Kyoon Choi, Director of DGIST’s Core Protein Resources Center, stated, "AI and supercomputing together set a new standard for protein analysis and drug design precision. This partnership is poised to deliver groundbreaking advancements in cancer treatment." National Assembly Member Seong Hoon Park underscored the national importance of this initiative: "The integration of AI and biotech is crucial for elevating South Korea’s global competitiveness in the bio-industry. The government will continue to provide unwavering support for these pioneering research efforts."

Envisioning a future shaped by precision medicine, J INTS BIO and its partners aim to build extensive cancer data infrastructures, providing a solid foundation for ongoing research and innovation. The consortium plans to unveil interim results from the "AI-Supercomputing-Based Personalized Lung Cancer Therapy" project at a major international conference in the first half of next year, showcasing the project’s far-reaching impact and potential.