A Phase I Safety and Feasibility Study of Cellular Immunotherapy for Extensive Stage Small Cell Neuroendocrine Prostate Cancer Using Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptor

This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ lentivirally transduced to express L1CAM-specific chimeric antigen receptor (CAR) and EGFRt mutation specific T cells and to see how well they work in treating patients with small cell neuroendocrine prostate cancer (SCNPC) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. Some solid tumor cells have an L1CAM protein on their surface, and T cells can be modified with a receptor, called a chimeric antigen receptor (CAR), to help recognize this protein and kill these tumor cells. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. These L1CAM mutation specific T cells may help the body's immune system identify and kill L1CAM locally advanced and unresectable or metastatic small cell neuroendocrine prostate cancers' tumor cells.

Start Date15 Apr 2025

Sponsor / Collaborator

Fred Hutchinson Cancer Research Center

[+1]

NCT06561347 / Not yet recruitingPhase 2IIT

A Phase 2 Multicenter Study of the Combination Zanubrutinib, Bendamustine, and Rituximab in Previously Untreated Waldenström Macroglobulinemia (ZEBRA Trial)

The purpose of this study is to determine the very good partial response (VGPR) or better rate in participants with Waldenström macroglobulinemia (WM).
The names of the study drugs involved in this study are as follows: zanubrutinib, bendamustine, and rituximab.

Start Date01 Dec 2024

Sponsor / Collaborator

The General Hospital Corp.

[+1]

NCT06557330 / Not yet recruitingPhase 2IIT

HM-225: Measurable Residual Disease (MRD) Guided De-intensification of Bendamustine/Rituximab (BR) for Indolent Non-Hodgkin Lymphoma

This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL.

Start Date01 Dec 2024

Sponsor / Collaborator

The Fox Chase Cancer Center

[+1]

100 Clinical Results associated with Bendamustine Hydrochloride

100 Translational Medicine associated with Bendamustine Hydrochloride

100 Patents (Medical) associated with Bendamustine Hydrochloride

2,860

Literatures (Medical) associated with Bendamustine Hydrochloride

01 Jan 2025·EUROPEAN JOURNAL OF HAEMATOLOGY

Reduced Intensity Conditioning Prior Autologous Stem Cell Transplantation in Elderly DLBCL Patients

Article

Author: Engelhardt, Monika ; Strüßmann, Tim ; Finke, Jürgen ; Hermes, Philipp ; Duque‐Afonso, Jesús ; Marks, Reinhard ; Ihorst, Gabriele ; Duyster, Justus

ABSTRACT:

High‐dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is widely used in patients with diffuse large B‐cell lymphoma. HDCT/ASCT is associated with increased morbidity in elderly/unfit patients. We retrospectively evaluated the use of reduced intensity conditioning in DLBCL patients. Our study included 146 patients aged 60 years and older treated at our institution between 2005 and 2019; 86 patients received standard intensity conditioning (SI group) with BEAM or TEAM (BCNU or thiotepa, etoposide, cytarabine, melphalan). Sixty patients received reduced intensity high‐dose conditioning (RI group) with BM (BCNU, melphalan, 43.3%), TM (thiotepa, melphalan, 16.7%), BCNU or busulfan thiotepa (38.4%), or bendamustine melphalan (1.7%). Median follow‐up was 62.4 months. We observed comparable toxicities in the SI and RI groups. The cumulative incidence of relapse at 3 years was higher in the RI group (30.8% vs. 23.4%, p = 0.034). There was no difference in nonrelapse mortality (NRM). In univariate analyses, SI vs. RI conditioning resulted in superior progression‐free survival (PFS) (HR 1.80 CI 1.11–2.92, p = 0.017) but not in superior overall survival (OS) (HR 1.48 CI 0.86–2.56, p = 0.152). On multivariate analysis, we observed no difference in PFS (HR 0.74 CI 0.40–1.38, p = 0.345) and a trend toward better OS with RI conditioning (HR 0.45 CI 0.22–0.94, p = 0.032). Age 60–69 versus ≥ 70 years and remission prior to ASCT were the only factors predicting better PFS. Factors associated with better OS were RI conditioning, age 60–69 versus ≥ 70 years, ECOG 0 versus ≥ 1 performance status, bulky disease, and prior lines 1 versus ≥ 2. In conclusion, RI conditioning prior to ASCT may be feasible in elderly patients and led to a comparable outcome when corrected for several significant confounders.

31 Dec 2024·JOURNAL OF MEDICAL ECONOMICS

Treatment patterns, healthcare resource utilization, and costs in Medicare patients with diffuse large B-cell lymphoma: a retrospective claims analysis (2015–2020)

Article

Author: Wang, Anthony ; Chhibber, Anindit ; Kalsekar, Anupama ; Mutebi, Alex ; Liang, Chenxue ; Keshishian, Allison ; He, Jing ; Jun, Monika P. ; Wang, Tongsheng ; Rivas Navarro, Fernando

AIMS:

To understand treatment patterns, healthcare resource utilization (HCRU), and the economic burden of diffuse large B-cell lymphoma (DLBCL) in elderly adults in the US.

MATERIALS AND METHODS:

This retrospective database analysis utilized US Centers for Medicare and Medicaid Services Medicare fee-for-service administrative claims data from 2015 to 2020 to describe DLBCL patient characteristics, treatment patterns, HCRU, and costs among patients aged ≥66 years. Patients were indexed at DLBCL diagnosis and required to have continuous enrollment from 12 months pre-index until 3 months post-index. HCRU and costs (USD 2022) are reported as per-patient per-month (PPPM) estimates.

RESULTS:

A total of 11,893 patients received ≥1-line (L) therapy; 1,633 and 391 received ≥2 L and ≥3 L therapies, respectively. Median (Q1, Q3) age at 1 L, 2 L, and 3 L initiation, respectively, was 76 (71, 81), 77 (72, 82), and 77 (72, 82) years. The most common therapy was R-CHOP (70.9%) for 1 L and bendamustine ± rituximab for 2 L (18.7%) and 3 L (17.4%). CAR T was used by 14.8% of patients in 3 L. Overall, 39.6% (1 L), 42.1% (2 L), and 47.8% (3 L) of patients had all-cause hospitalizations. All-cause mean (median [Q1-Q3]) costs PPPM during each line were $22,060 ($20,121 [$16,676-$24,597]) in 1 L, $30,027 ($20,868 [$13,416-$31,016]) in 2 L, and $47,064 ($25,689 [$15,555-$44,149]) in 3 L, with increasing costs driven primarily by inpatient expenses. Total all-cause 3 L mean (median [Q1-Q3]) costs PPPM for patients with and without CAR T were $153,847 ($100,768 [$26,534-$253,630]) and $28,466 ($23,696 [$15,466-$39,107]), respectively.

CONCLUSIONS:

No clear standard of care exists in 3 L therapy for older adults with relapsed/refractory DLBCL. The economic burden of DLBCL intensifies with each progressing line of therapy, thus underscoring the need for additional therapeutic options.

31 Dec 2024·JOURNAL OF MEDICAL ECONOMICS

Cost-effectiveness analysis of mosunetuzumab for treatment of relapsed or refractory follicular lymphoma after two or more lines of systemic therapy in the United States

Article

Author: Sanchez Alvarez, Javier ; Lin, Shih-Wen ; Parisé, Hélène ; Di Maio, Danilo ; Zuk, Eric ; Kim, Eunice ; Matasar, Matthew ; Shapouri, Sheila

AIMS:

Mosunetuzumab has received accelerated approval by the US Food and Drug Administration for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. We evaluated the cost-effectiveness of mosunetuzumab for the treatment of R/R FL from a US private payer perspective.

MATERIALS AND METHODS:

A partitioned survival model simulated lifetime costs and outcomes of mosunetuzumab against seven comparators: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), tazemetostat (taz, EZH2 wild-type only), rituximab plus lenalidomide (R-Len) or bendamustine (R-Benda), obinutuzumab plus bendamustine (O-Benda), and a retrospective real-world cohort (RW) based on current patterns of care derived from US electronic health records (Flatiron Health). Efficacy data for mosunetuzumab were from the pivotal Phase II GO29781 trial (NCT02500407). Relative treatment efficacy was estimated from indirect treatment comparisons (ITCs). Costs included were related to treatment, adverse events, routine care, and terminal care. Except for drug costs (March 2023), all costs were inflated to 2022 US dollars. Costs and quality-adjusted life-years (QALYs) were used to calculate incremental cost-effectiveness ratios (ICERs). Net monetary benefit (NMB) was calculated using a willingness-to-pay (WTP) threshold of $150,000/QALY.

RESULTS:

Mosunetuzumab dominated taz, tisa-cel, and axi-cel with greater QALYs and lower costs. Mosunetuzumab was projected to be cost-effective against R-Benda, O-Benda, and RW with ICERs of $78,607, $42,731, and $21,434, respectively. Mosunetuzumab incurred lower costs but lower QALYs vs. R-Len. NMBs showed that mosunetuzumab was cost-effective against comparators except R-Len.

LIMITATIONS:

Without head-to-head comparative data, the model had to rely on ITCs, some of which were affected by residual bias. Model inputs were obtained from multiple sources. Extensive sensitivity analyses assessed the importance of these uncertainties.

CONCLUSION:

Mosunetuzumab is estimated to be cost-effective compared with approved regimens except R-Len for the treatment of adults with R/R FL.

203

News (Medical) associated with Bendamustine Hydrochloride

18 Dec 2024

·www.prnewswire.com

Cancer Care Disruptions Highlight Growing Demand for Innovative Oncology Treatments

USA News Group Commentary Issued on behalf of Oncolytics Biotech Inc. VANCOUVER, BC, Dec. 18, 2024 /PRNewswire/ -- USA News Group News Commentary – The American Cancer Society recently released its Advances in Oncology – 2024 Research Highlights report that highlighted how their scientists continued to set the standard for research and innovation over the course of the year. However, along with the report's optimism, the American Cancer Society also recently released a study finding that early-onset colorectal cancer cases are surging globally, signaling an alarming trend. A new article published in Nature showed that the COVID-19 pandemic severely disrupted cancer care, causing delays in diagnosis, treatment, and screening services, which likely led to more advanced disease stages, poorer survival outcomes, and significant challenges in accurately interpreting long-term cancer survival data. In the world of oncology, there are still several challenges that need to be addressed and new treatments to be rolled out, but thankfully, there have been several recent developments coming out from innovators, including O ncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), Cardiff Oncology, Inc. (NASDAQ: CRDF), OS Therapies, Inc. (NYSE-American: OSTX), Checkpoint Therapeutics, Inc. (NASDAQ: CKPT), and Eli Lilly and Company (Lilly) (NYSE: LLY). The article continued: Not long ago, the American Cancer Society sounded the alarm on a surging rise in cancer diagnoses and fatalities among younger. For the industry targeting the alarming issue, analysts at Exactitude Consultancy project the Cancer Immunotherapy Market to expand at a 12.84% CAGR, reaching $258.22 billion by the end of 2031, further solidifying oncology as a dynamic and evolving sector. Oncolytics Biotech® to Present Promising Pelareorep Data in Pancreatic and Anal Cancers at ASCO GI Symposium Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, today announced the presentation of two data sets through two abstracts showcasing pelareorep's potential in difficult-to-treat gastrointestinal cancers, which were accepted and will be presented at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco January 23-25, 2025. "We are enthusiastic about pelareorep's applicability across multiple gastrointestinal cancer indications, including pancreatic and anal cancer," said Tom Heineman, M.D., Ph.D., Chief Medical Officer of Oncolytics. "Pelareorep engages patients' immune systems to help make commonly used chemotherapies and checkpoint inhibitors, such as atezolizumab, more effective in fighting cancer. This offers the promise of delaying disease progression and improving survival in patients with these devasting diseases. Given the versatility of pelareorep, we see multiple clinical and regulatory options for bringing this promising medicine to patients." Oncolytics will present two key data sets from the GOBLET study, with preliminary safety and tumor response results for the relapsed anal carcinoma cohort treated with pelareorep and atezolizumab presented in Poster Session C on January 25, 2025, from 7:00 to 7:55 a.m. PT. Additionally, results from the safety run-in phase for first-line metastatic pancreatic ductal adenocarcinoma patients treated with pelareorep, modified FOLFIRINOX, with and without atezolizumab will be presented in Poster Session B on January 24, 2025, from 11:30 a.m. to 1:00 p.m. PT. Both abstracts will be available on the ASCO Gastrointestinal Cancers Symposium website at 5:00 p.m. ET on January 21, 2025. CONTINUED… Read this and more news for Oncolytics Biotech at: In other recent industry developments and happenings in the market include: Cardiff Oncology, Inc. (NASDAQ: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, recently announced positive initial data from CRDF-004, a randomized, Phase 2 clinical trial evaluating onvansertib in combination with standard-of-care (SoC) in patients with first-line RAS-mutated metastatic colorectal cancer (mCRC). Efficacy and safety data are for all evaluable patients as of a November 26, 2024, data cut-off date, and all efficacy data are determined by a blinded, independent central review (BICR) of each patient's tumor scan. "We are highly encouraged by the robust efficacy signal and favorable safety profile observed with onvansertib plus standard-of-care from the first 30 evaluable patients in our randomized first-line RAS-mutated mCRC CRDF-004 trial," said Fairooz Kabbinavar, MD, FACP, Chief Medical Officer of Cardiff Oncology. "Our data shows an objective response rate of 64% in patients receiving the 30 mg dose of onvansertib in combination with standard of care, significantly higher than the 33% objective response rate observed in the control arms of standard of care alone. In addition, as can be seen in the spider plots, we are observing deeper tumor response in patients receiving the 30mg dose of onvansertib compared to those receiving the 20mg dose with similar safety profiles for both doses." OS Therapies, Inc. (NYSE-American: OSTX), a clinical-stage cancer immunotherapy and antibody-drug conjugate biotechnology company, recently reported its Q3 2024 financial results for the quarter and provided a business update. Within the quarter, OS Therapies completed dosing all patients in its potentially pivotal Phase 2b clinical trial of OST-HER2 for resected, recurrent osteosarcoma and is preparing to release topline data in December. The company also joined Johnson & Johnson's JLABS program, completed its IPO on the NYSE American, and is in active discussions with the FDA regarding Breakthrough Therapy Designation for OST-HER2. "The third quarter was pivotal for OS Therapies as we completed our initial public offering and finished dosing the final patient enrolled in our Phase 2b clinical trial of OST-HER2 in resected, recurrent osteosarcoma," said Paul Romness, MHP, Chairman and CEO of OS Therapies. "We are now looking forward to releasing topline data in December and then engaging with the FDA regarding getting this potentially life-saving cancer immunotherapy to patients that have no other potential treatment options as quickly as possible." Checkpoint Therapeutics, Inc. (NASDAQ: CKPT), a commercial-stage immunotherapy and targeted oncology company focused on novel treatments for patients with solid tumor cancers, recently announced that the FDA approved its UNLOXCYT™ (cosibelimab-ipdl) for the treatment of adults with metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC who are not candidates for curative surgery or curative radiation. UNLOXCYT is the first and only programmed death ligand-1 (PD-L1) blocking antibody to receive FDA marketing approval for this indication. "[This] FDA approval of UNLOXCYT – the first marketing approval for our company – is a significant milestone both for Checkpoint and for patients with advanced cSCC," said James Oliviero, President and CEO of Checkpoint. "This approval marks Checkpoint's transformation to a commercial-stage company, with the opportunity to compete in a U.S. market estimated to exceed $1 billion annually, where we believe UNLOXCYT offers a differentiated treatment option versus available therapies by binding to PD-L1, rather than programmed death receptor-1 (PD-1), to release the inhibitory effects of PD-L1 on the anti-tumor immune response. Additionally, UNLOXCYT has demonstrated the ability to induce antibody-dependent cell-mediated cytotoxicity (ADCC), another potential differentiating feature of the drug compared to existing marketed therapies for patients with cSCC." Eli Lilly and Company (Lilly) (NYSE: LLY), a medicine company turning science into healing to make life better for people around the world, recently announced results from its Phase 3 BRUIN CLL-321 trial, which tested pirtobrutinib, a next-generation treatment for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously been treated with a similar type of drug. The study showed that pirtobrutinib significantly reduced the risk of disease progression or death by 46% compared to standard treatments (idelalisib plus rituximab or bendamustine plus rituximab). These promising results were presented at the 66th American Society of Hematology (ASH) Annual Meeting. "BRUIN CLL-321 is the only randomized CLL or SLL study ever conducted exclusively in the BTK-inhibitor pre-treated population, where there is significant need for new treatment options, and these data illustrate pirtobrutinib's ability to meaningfully delay disease progression and time to next treatment in this setting," said David Hyman, M.D., Chief Medical Officer of Lilly. "This is the first in our suite of randomized Phase 3 trials for pirtobrutinib to readout and we look forward to continuing to build the body of evidence supporting the role of pirtobrutinib in advancing care for people with B-cell malignancies." Source: CONTACT: USA NEWS GROUP [email protected] (604) 265-2873 DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. USA News Group is a wholly-owned subsidiary of Market IQ Media Group, Inc. ("MIQ"). MIQ has been paid a fee for Oncolytics Biotech Inc. advertising and digital media from the company directly. There may be 3rd parties who may have shares of Oncolytics Biotech Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ own shares of Oncolytics Biotech Inc. which were purchased in the open market, and reserve the right to buy and sell, and will buy and sell shares of Oncolytics Biotech Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved by Oncolytics Biotech Inc.; this is a paid advertisement, we currently own shares of Oncolytics Biotech Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. SOURCE USA News Group WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Drug ApprovalImmunotherapyClinical ResultASCO

18 Dec 2024

·www.investor.jnj.com

Johnson & Johnson submits application to the European Medicines Agency seeking approval of a new indication for IMBRUVICA® (ibrutinib) in adult patients with previously untreated mantle cell lymphoma (MCL) who are eligible for autologous stem cell tr

The European MCL Network Phase 3 TRIANGLE study, evaluated ibrutinib in combination with induction immunochemotherapy, both with and without an autologous stem cell transplant, followed by 24 months fixedduration ibrutinib therapy1 Both ibrutinib-based regimens, transplant-free and with transplant, delivered clinically meaningful improvement in efficacy compared to the current standard of care of induction immunochemotherapy followed by transplant2 BEERSE, BELGIUM (18 December 2024) – Janssen-Cilag International NV, a Johnson & Johnson company, today announced the submission of a Type II variation application to the European Medicines Agency (EMA). The submission seeks approval for an indication extension of IMBRUVICA® (ibrutinib) in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL), who are eligible for autologous stem cell transplant (transplant). This regulatory submission is supported by data from the TRIANGLE study, conducted by the European MCL Network. “Mantle cell lymphoma remains an incurable and challenging disease to treat, particularly in younger patients in need of durable frontline options,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Johnson & Johnson Innovative Medicine. “The TRIANGLE study demonstrates ibrutinib's potential to replace or compliment a transplantbased regimen, offering eligible patients a more effective path to long term remission and representing the first major step forward in frontline mantle cell lymphoma treatment in years.” The proposed indication is supported by results from the Phase 3 TRIANGLE study (NCT02858258) which investigated 870 patients across three treatment arms: standard induction immunochemotherapy followed by transplant, induction immunochemotherapy plus ibrutinib followed by transplant and 2-year fixed-duration ibrutinib therapy, and induction immunochemotherapy plus ibrutinib without transplant, followed by 2-year fixed-duration ibrutinib therapy.2,3 Prolonged efficacy and safety data from the TRIANGLE study were recently presented by the principal investigator Prof. Dr. Martin Dreyling, Ludwig Maximilian University of Munich, as an oral presentation at the 2024 American Society of Hematology (ASH) Annual Meeting.3 “At Johnson & Johnson, we are committed to investing in innovation that transforms clinical outcomes for those living with complex blood cancers, including mantle cell lymphoma,” said Jessica Vermeulen, Vice President, Oncology Late Development, Johnson & Johnson Innovative Medicine. “Today’s submission to the EMA could represent a pivotal step in moving beyond transplant as the frontline standard of care for younger patients with mantle cell lymphoma.” About Ibrutinib Ibrutinib is a once-daily oral medication that is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.4 Ibrutinib blocks the BTK protein, which is needed by normal and abnormal B-cells, including specific cancer cells, to multiply and spread.5 By blocking BTK, ibrutinib may help move abnormal B-cells out of their nourishing environments and inhibits their proliferation. 6 Ibrutinib is approved in more than 100 countries and has been used to treat more than 300,000 patients worldwide.7 There are more than 50 companysponsored clinical trials, including 18 Phase 3 studies, over 11 years evaluating the efficacy and safety of ibrutinib.4,8 In October 2021, ibrutinib was added to the World Health Organization’s Model Lists of Essential Medicines (EML), which refers to medicines that address global health priorities and which should be available and affordable for all.9 Ibrutinib was first approved by the European Commission (EC) in 2014, and approved indications to date include:4 As a single agent or in combination with rituximab or obinutuzumab or venetoclax for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) As a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy As a single agent for the treatment of adult patients with relapsed or refractory MCL As a single agent for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy. In combination with rituximab for the treatment of adult patients with WM For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics. About Mantle Cell Lymphoma (MCL) MCL is an aggressive type of blood cancer that originates from the B lymphocytes, a functional component of the human immune system.10 The overall incidence of MCL globally is approximately 1-2 cases per 100,000 persons per year and it has a higher prevalence in men than women.11 MCL typically affects individuals at 65-years of age at diagnosis.11 While patient outcomes have dramatically improved over the latest few decades, MCL remains a difficult disease to treat with many patients relapsing or becoming resistant to therapy.11 About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at www.innovativemedicine.jnj.com/emea. Follow us at www.linkedin.com/company/jnj-innovative-medicine-emea. Janssen-Cilag International NV, Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen Biologics B.V. and Janssen Research & Development, LLC are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements  This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of ibrutinib. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialise, actual results could vary materially from the expectations and projections of Janssen-Cilag International NV, Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen Research & Development, LLC, Janssen Biologics B.V. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behaviour and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at https://www.sec.gov/, http://www.jnj.com/ or on request from Johnson & Johnson. None of Janssen-Cilag International NV, Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen Research & Development, LLC, Janssen Biologics B.V. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. 1 ClinicalTrials.gov. ASCT After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma. NCT02858258. Available at: https://clinicaltrials.gov/study/NCT02858258. Last accessed: December 2024. 2Dreyling et al., Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network. The Lancet, 2024; 403:10441:2293 - 2306 3Dreyling at al., Role of Autologous Stem Cell Transplantation in the Context of Ibrutinib-Containing First-Line Treatment in Younger Patients with Mantle Cell Lymphoma: Results from the Randomized Triangle Trial By the European MCL Network. Oral presentation. Abstract # 240. 2024 American Society of Hematology Annual Meeting. 4European Medicines Agency. IMBRUVICA Summary of Product Characteristics. September 2023. Available at: https://www.ema.europa.eu/en/documents/product-information/imbruvica-epar-product-information_en.pdf. Last accessed: December 2024. 5Turetsky A, et al. Single cell imaging of Bruton's tyrosine kinase using an irreversible inhibitor. Sci Rep. 2014;4:4782 6de Rooij MF, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012. 119(11):2590-2594 7 J&J Data on File (RF-419273). Global number of cumulative patients treated with Ibrutinib since launch. June 2024. 8 Pollyea DA, et al. A Phase I Dose Escalation Study of the Btk Inhibitor PCI-32765 in Relapsed and Refractory B Cell Non-Hodgkin Lymphoma and Use of a Novel Fluorescent Probe Pharmacodynamic Assay. Blood. 2009. 114(22): 3713 9World Health Organization. WHO prioritizes access to diabetes and cancer treatments in new Essential Medicines Lists. Available at: https://www.who.int/news/item/01-10-2021-who-prioritizes-access-to-diabetes-and-cancer-treatments-in-new-essential-medicines-lists. Last accessed: December 2024. 10Jain P. and Wang M. L., Mantle cell lymphoma in 2022-A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments, American Journal of Hematology. 2022; 97;5:638–56. 11Dreyling, M. et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 2017; 28:62-71 Media contact: Jenni Mildon JMildon@its.jnj.com +44 7920 418 552 Investor contact: Lauren Johnson   investor-relations@its.jnj.com

ImmunotherapyPhase 3Drug ApprovalASHClinical Result

09 Dec 2024

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Phase 3 results for Lilly's Jaypirca® (pirtobrutinib) in covalent BTK inhibitor pre-treated chronic lymphocytic leukemia or small lymphocytic lymphoma to be presented at the 2024 ASH Annual Meeting

Results from BRUIN CLL-321 show Lilly's pirtobrutinib reduced the risk of disease progression or death by 46% compared to idelalisib plus rituximab or bendamustine plus rituximab Pirtobrutinib prolonged the time to next treatment or death by a median of 23.9 months compared to 10.9 months in the control arm BRUIN CLL-321 is the first randomized Phase 3 study in CLL ever conducted exclusively in patients previously treated with a BTK inhibitor INDIANAPOLIS, Dec. 9, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced results from the Phase 3 BRUIN CLL-321 trial evaluating pirtobrutinib, a non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor in adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor. The study's primary endpoint of progression-free survival (PFS) was met at primary analysis1, demonstrating pirtobrutinib was superior to investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR), based on independent review committee (IRC) assessment. Today's updated results corresponding to the final prespecified analysis, demonstrate consistent improvement in PFS for patients treated with pirtobrutinib, with a reduction in risk of relapse, disease or death by 46% compared to IdelaR or BR. These data will be presented in an oral presentation at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition. "These results demonstrate the ability of pirtobrutinib to deliver clinically meaningful outcomes in a post-covalent BTK inhibitor setting, which is especially remarkable given the poor prognosis for the patient population enrolled in BRUIN CLL-321," said Jeff Sharman, M.D., Disease Chair, Lymphoma Research Executive Committee, SCRI at Willamette Valley Cancer Institute and Research Center, and one of the principal investigators of the BRUIN CLL-321 trial. "These data also show that pirtobrutinib can significantly prolong the time to next treatment with a median of approximately two years. Coupled with the safety results, the BRUIN CLL-321 data are important as we consider treatment sequencing for this setting." BRUIN CLL-321 enrolled 238 patients who were randomized to receive pirtobrutinib monotherapy (n=119) or investigator's choice of IdelaR or BR (n=119). Patients across both arms received a median of three prior lines of therapy, with all patients having received at least one prior covalent BTK inhibitor. Approximately half of the patients had also received a venetoclax-containing regimen. Reflective of the poor prognosis of patients enrolled in this study, a high proportion of patients presented with high-risk features indicative of aggressive disease, including TP53 mutation and/or 17p deletion, unmutated IGHV status and complex karyotype. Efficacy results are based on IRC assessment of the intent-to-treat (ITT) population and utilize an Aug. 29, 2024 data cutoff date. Crossover to the pirtobrutinib arm was allowed after IRC-confirmed disease progression. At median follow-up of approximately 19 months, median PFS was 14.0 months for the pirtobrutinib arm compared to 8.7 months for the control arm (HR=0.54 [95% CI, 0.39-0.75]). PFS results were consistent across key subgroups associated with a poor prognosis, including patients who received prior venetoclax and those with TP53 mutations and/or 17p deletions, unmutated IGHV status and complex karyotype. Pirtobrutinib also demonstrated clinically meaningful improvements in other secondary endpoints such as investigator-assessed PFS (median PFS: 15.3 vs. 9.2 months; HR=0.48 [95% CI, 0.34-0.67]), event-free survival (EFS) (median EFS: 14.1 vs. 7.6 months; HR=0.39 [95% CI, 0.28-0.53]), and time to next treatment (TTNT) or death (median TTNT: 23.9 vs. 10.9 months; HR=0.37 [95% CI, 0.25-0.52]). Specifically, among patients in the control arm who were eligible for crossover, 76% (n=50/66) crossed over to receive pirtobrutinib. Multiple analyses that adjust for the effect of crossover demonstrate trends in favor of pirtobrutinib (Inverse Probability Censored Weighting methodology: HR= 0.89 [95% CI, 0.52-1.53]; two-stage Accelerated Failure Time methodology: HR=0.77 [95% CI, 0.45-1.26]). The overall safety profile for patients treated with pirtobrutinib in BRUIN CLL-321 was consistent with safety data from the Phase 1/2 BRUIN study, including adverse events of special interest. In the Phase 3 study, pirtobrutinib treatment was associated with fewer grade 3 or higher treatment-emergent adverse events (TEAEs) and fewer treatment discontinuations due to adverse events compared to IdelaR or BR. When adjusting for exposure, the incidence rate of TEAEs was overall lower in patients receiving pirtobrutinib compared to IdelaR or BR. "BRUIN CLL-321 is the only randomized CLL or SLL study ever conducted exclusively in the BTK-inhibitor pre-treated population, where there is significant need for new treatment options, and these data illustrate pirtobrutinib's ability to meaningfully delay disease progression and time to next treatment in this setting," said David Hyman, M.D., chief medical officer, Lilly. "This is the first in our suite of randomized Phase 3 trials for pirtobrutinib to readout and we look forward to continuing to build the body of evidence supporting the role of pirtobrutinib in advancing care for people with B-cell malignancies." Lilly is committed to the ongoing investigation of pirtobrutinib in people living with hematologic malignancies. The BRUIN clinical trial program consists of six clinical studies, four of which are Phase 3 studies evaluating pirtobrutinib in CLL/SLL. For more information on the BRUIN Phase 3 clinical trial program, please visit clinicaltrials.gov. Pirtobrutinib is approved as Jaypirca® under the U.S. Food and Drug Administration's (FDA) Accelerated Approval pathway for the treatment of adult patients with CLL/SLL who have received at least two prior lines of therapy, including a BTK inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor and adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK 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. About BRUIN CLL-321 BRUIN CLL-321 is a Phase 3, randomized, open-label study of pirtobrutinib versus investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) in BTK inhibitor pre-treated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). The trial enrolled 238 patients, who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily) or investigator's choice of either IdelaR or BR per labeled doses. This trial's primary endpoint is progression-free survival (PFS) per 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria, as assessed by blinded independent review committee (IRC). Secondary endpoints include PFS, as assessed by investigator; overall response rate (ORR) and duration of response (DoR); event-free survival; overall survival (OS) and time to next treatment (TTNT); safety and tolerability; and patient-reported outcomes (PRO). About Pirtobrutinib Pirtobrutinib 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.2 BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation, and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas, including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).3,4 Pirtobrutinib was developed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, and preserve activity in the presence of the C481 acquired resistance mutations. About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma CLL and SLL are forms of slow-growing non-Hodgkin lymphoma that develop from white blood cells known as lymphocytes.5,6 CLL is one of the most common types of leukemia in adults.5 In the U.S., CLL accounts for about one-quarter of the new cases of leukemia and there will be approximately 20,700 new cases of CLL diagnosed this year.5,7 SLL is identical to CLL from a pathologic and immunophenotypic standpoint, with the main difference between them being the location of the cancer cells.5 In CLL, the cancer cells are present in the blood, and in SLL, the cancer cells are found in the lymph nodes.5 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. PT HCP ISI MCL_CLL AA JUN2024 Please see Prescribing Information and Patient Information for Jaypirca. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY Jaypirca® is a registered trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates. © Lilly USA, LLC 2024. ALL RIGHTS RESERVED. Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Jaypirca® (pirtobrutinib) as a potential treatment for adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that studies will be completed as planned, that future study results will be consistent with the results to date, that Jaypirca will prove to be a safe and effective treatment for relevant indications, or that Jaypirca will receive additional regulatory approvals or be commercially successful. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. Sharman JP, Munir T, Grosicki S, et al. 886 BRUIN CLL-321: Randomized Phase III Trial of Pirtobrutinib Versus Idelalisib Plus Rituximab (IdelaR) or Bendamustine Plus Rituximab (BR) in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Abstract presented at: American Society of Hematology Annual Meeting and Exposition; December 9, 2024; San Diego, CA. Session 642. Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901. doi:10.1016/S0140-6736(21)00224-5 Hanel W, Epperla N. Emerging therapies in mantle cell lymphoma. J Hematol Oncol. 2020;13(1):79. Published 2020 Jun 17. doi:10.1186/s13045-020-00914-1 Gu D, Tang H, Wu J, Li J, Miao Y. Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies. J Hematol Oncol. 2021;14(1):40. Published 2021 Mar 6. doi:10.1186/s13045-021-01049-7 Mukkamalla SKR, Taneja A, Malipeddi D, et al. Chronic Lymphocytic Leukemia. [Updated 2023 Feb 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: The Leukemia and Lymphoma Society. NHL Subtypes. Access here: . Accessed on October 25, 2023. NIH National Cancer Institute. Cancer Stat Facts: Leukemia – Chronic Lymphocytic Leukemia (CLL). Access here: . Accessed on October 3, 2023. SOURCE Eli Lilly and Company WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 3Drug ApprovalASHAccelerated Approval

100 Deals associated with Bendamustine Hydrochloride

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KEGG	Wiki	ATC	Drug Bank
D07085	Bendamustine Hydrochloride	L01AA09	DB06769

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Diffuse Large B-Cell Lymphoma	JP	SymBio Pharmaceuticals Ltd.	28 Apr 2021
Lymphoid Leukemia	JP	SymBio Pharmaceuticals Ltd.	26 Aug 2016
Indolent B-Cell Non-Hodgkin Lymphoma	US	Eagle Pharmaceuticals, Inc.	07 Dec 2015
Mantle-Cell Lymphoma	JP	SymBio Pharmaceuticals Ltd.	27 Oct 2010
Indolent Non-Hodgkin Lymphoma	DE	Pharma& Schweiz GmbH	15 Jul 2010
Multiple Myeloma	DE	Pharma& Schweiz GmbH	15 Jul 2010
B-Cell Lymphoma	US	Cephalon, Inc.	31 Oct 2008
Non-Hodgkin Lymphoma	US	Cephalon, Inc.	31 Oct 2008
Chronic Lymphocytic Leukemia	US	Cephalon, Inc.	20 Mar 2008
Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma	CA	Dr. Reddy's Laboratories Ltd.	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
B-cell lymphoma refractory	Phase 3	CN	Shandong Lanjin Biological Engineering Co., Ltd.	01 Apr 2010
Recurrent Chronic Lymphoid Leukemia	Phase 3	DE	Mundipharma Research GmbH & Co. KG	01 Sep 2001
Classical Hodgkin's Lymphoma	Phase 2	US	Bristol Myers Squibb Co.	26 Nov 2018
Refractory Classic Hodgkin Lymphoma	Phase 2	US	Bristol Myers Squibb Co.	28 Mar 2017
Refractory Classic Hodgkin Lymphoma	Phase 2	CA	Bristol Myers Squibb Co.	28 Mar 2017
Refractory Classic Hodgkin Lymphoma	Phase 2	CZ	Bristol Myers Squibb Co.	28 Mar 2017
Refractory Classic Hodgkin Lymphoma	Phase 2	FR	Bristol Myers Squibb Co.	28 Mar 2017
Refractory Classic Hodgkin Lymphoma	Phase 2	DE	Bristol Myers Squibb Co.	28 Mar 2017
Refractory Classic Hodgkin Lymphoma	Phase 2	IE	Bristol Myers Squibb Co.	28 Mar 2017
Refractory Classic Hodgkin Lymphoma	Phase 2	IT	Bristol Myers Squibb Co.	28 Mar 2017

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2024	Not Applicable	Follicular Lymphoma	-	Tazemetostat 800mg BID	hdcljtmneb(wabfrbsqve) = leukopenia (n=2), neutropenia (n=1), anemia (n=1), atrial fibrillation (n=1), bone pain (n=1), infection (n=2), and infusion related reaction (n=1) sezetsrnav (eloljcofut ) View more	-	09 Dec 2024
ASH2024	Not Applicable	Mantle-Cell Lymphoma	-	Bendamustine/Rituximab (BR)	ouvrayggpr(uiyesxhlui) = ulbnjzkltu zbxjwhdmdl (wvwovlwubd, 59.8 - 79.7) View more	-	09 Dec 2024
ASH2024	Not Applicable	Indolent B-Cell Non-Hodgkin Lymphoma	-	Bendamustine Rituximab	aamkrszzja(hitzauwket) = djgxgwiojg xjxdcujmch (gngomkrobn, 8.6 - 10.4)	-	08 Dec 2024
ASH2024	Not Applicable	Indolent B-Cell Non-Hodgkin Lymphoma	-	Placebo	aamkrszzja(hitzauwket) = klhkofwtav xjxdcujmch (gngomkrobn, 5.9 - 9.4)	-	08 Dec 2024
NCT04663347 (EPCORE NHL-2, ASH2024) Manual	Phase 1/2	Follicular Lymphoma First line	25	Epcoritamab + Bendamustine + Rituximab	ktwvvjccrs(yzwmlydkeg) = modpsbzfvp iwnqmqvrxy (pyopnemttc ) View more	Positive	07 Dec 2024
ASH2024	Not Applicable	Mantle-Cell Lymphoma	-	Acalabrutinib plus bendamustine-rituximab (ABR)	kcakpumsbw(mqnkvaxjao) = zjmynothiy rjdiofmswc (mwhvwetzdo ) View more	-	07 Dec 2024
ASH2024	Not Applicable	Mantle-Cell Lymphoma	-	Placebo plus bendamustine-rituximab (PBR)	kcakpumsbw(mqnkvaxjao) = gapdkwhpbs rjdiofmswc (mwhvwetzdo ) View more	-	07 Dec 2024
NCT03311126 (CTgov)	Phase 2	Mantle-Cell Lymphoma	21	Bendamustine+Obinutuzumab	ovmpeixqcr(hmorgrbutc) = sfhtiwalcg fjpedkgbzx (sohenxfdsv, xsyagevemf - siezfmgjuz) View more	-	24 Oct 2024
NCT02002598 (CTgov)	Phase 1/2	Multiple Myeloma	23	Bendamustine+Carfilzomib+Dexamethasone	dzxerngfem(xpzqytuzzd) = kkaedjihsq xoqyjwjtjr (kzcdzzluuo, eojzwornmu - glaavnkgrl) View more	-	19 Sep 2024
SOHO2024	Not Applicable	Follicular Lymphoma	-	Bendamustine-rituximab (BR) and rituximab maintenance	ubrjouupfx(dvayhdfzvf) = mcokifzfje gjienmybxe (bnevsmoulr, 68 - 76) View more	-	04 Sep 2024
SOHO2024	Not Applicable	B-cell lymphoma refractory	-	Obinutuzumab+Bendamustine+Lenalidomide	jelhmbopdr(hamcpfoeyi) = 40% mhsnupxwlv (runhzvalai ) View more	-	04 Sep 2024
NCT00974233 (Pubmed \| Leuk Lymphoma)	Phase 2	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma Maintenance	-	Bendamustine + Rituximab	vwkuqesktf(jfdyequfoc) = lzgntthvxb wavxqgipsg (mmcpfskrzt ) View more	Positive	10 Jun 2024
NCT00974233 (Pubmed \| Leuk Lymphoma)	Phase 2		-	Lenalidomide + Rituximab	vwkuqesktf(jfdyequfoc) = afvrvexrrr wavxqgipsg (mmcpfskrzt )	Positive	10 Jun 2024

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