Janssen Presents First Data from MajesTEC-2 Trial of TECVAYLI®▼ (teclistamab) in Combination with DARZALEX® (daratumumab) Subcutaneous (SC) Formulation and Lenalidomide in Relapsed or Refractory Multiple Myeloma

Initial Phase 1b study results show clinical activity with immune-based triplet therapy regimen1 BEERSE, Belgium, Dec. 10, 2022 (GLOBE NEWSWIRE) — The Janssen Pharmaceutical Companies of Johnson & Johnson announced today new results from a cohort of the Phase 1b MajesTEC-2 study of TECVAYLI®▼ (teclistamab), the first European Commission approved BCMAxCD3 bispecific T-cell engager antibody, in combination with DARZALEX® (daratumumab) subcutaneous (SC) formulation and lenalidomide.1,2,3 According to the results, the immune-based triplet therapy regimen had a manageable safety profile with no unexpected safety signals observed.1 A very good partial response (VGPR) or better was achieved by 90.3 percent of patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy, including a proteasome inhibitor and immunomodulatory drug, with responses deepening over time.1 These data were presented during the 2022 American Society of Hematology (ASH) Annual Meeting, taking place in New Orleans, U.S. (Abstract #160).1 “These results show the potential of the combination of the bispecific BCMA-directed antibody teclistamab with the anti-CD38 antibody daratumumab and lenalidomide in the treatment of patients with relapsed or refractory multiple myeloma,” said Emma Searle, M.D., Ph.D., Consultant Haematologist and Honorary Senior Lecturer, The Christie Hospital and University of Manchester, England, and study investigator.† “This is the first presentation of data from a teclistamab-based triplet regimen, and we are eager to better understand how this combination may benefit patients through ongoing clinical studies.” At a median follow-up of 8.4 months (range, 1.1-12.9), the overall response rate (ORR) was 93.5 percent.1 Among all patients in the trial, VGPRs or better were achieved by 90.3 percent of patients, and 54.8 percent of patients achieved a complete response (CR) or better.1 Median time to response was one month (range, 0.7-3.3). The median time to CR or better was three months (range, 1.0-10.4).1 At data cut-off, 80.6 percent of patients remained progression-free and on treatment.1 Responses deepened over time, and median duration of response had not been reached.1 “Multiple myeloma is a complex disease and despite treatment advances in recent years, remains incurable. Our goal is to improve and expand on the options currently available to patients, in this area of high unmet medical need,” said Edmond Chan, MBChB M.D. (Res), EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. “The data presented at ASH indicate the potential of this combination regimen for people living with multiple myeloma who are in need of new treatment options, and aligns with our vision of tackling the disease with novel, complementary and combinable options across the disease continuum. We are committed to investigating this regimen further.” MajesTEC-2 (NCT04722146) is a multicohort study.1,2 The primary objective of this cohort was to understand if the immunomodulatory effects of daratumumab SC and lenalidomide may enhance the function of teclistamab, potentially resulting in enhanced antimyeloma activity in a broader population of patients than currently indicated for.1,2 The MajesTEC-7 study (NCT05552222) will examine the potential of this combination compared to the combination of daratumumab, lenalidomide and dexamethasone, in patients with newly diagnosed multiple myeloma.4 The most frequent haematological adverse events (AEs) observed in the study included neutropenia (84.4 percent any grade, 78.1 percent grade 3/4) and thrombocytopenia (25 percent any grade, 15.6 percent grade 3/4).1 The most frequent non-haematological AE was cytokine release syndrome (CRS) (81.3 percent, all grade 1/2); 97 percent of CRS events occurred during cycle 1.1 Other common non-haematological AEs included fatigue (46.9 percent any grade, 6.3 percent grade 3/4); diarrhoea (46.9 percent any grade, none grade 3/4); cough (40.6 percent any grade, 3.1 percent grade 3/4); COVID-19 (37.5 percent any grade, 12.5 percent grade 3/4); insomnia (37.5 percent any grade, 3.1 percent grade 3/4); hypophosphataemia (31.3 percent any grade, 6.3 percent grade 3/4); pyrexia (31.3 percent any grade, 3.1 percent grade 3/4); upper respiratory tract infection (31.3 percent any grade, none grade 3/4); nausea (31.3 percent any grade, none grade 3/4); increased alanine aminotransferase (ALT) (28.1 percent any grade, 9.4 percent grade 3/4) and pneumonia (25 percent any grade, 15.6 percent grade 3/4).1 Two patients discontinued therapy due to an AE (COVID-19),1 considered to be unrelated to the study by investigator assessment.5 Infections were common among patients in the study and the majority were low grade (90.6 percent any grade, 37.5 percent grade 3/4).1   New Data from the Phase 1/2 MajesTEC-1 Study Evaluating Teclistamab in Relapsed or Refractory Multiple Myeloma Patients New correlative analyses were also presented from the MajesTEC-1 study (NCT04557098).6,7 Data from these analyses may be used to help better understand baseline immune and tumour correlatives associated with outcomes in patients treated with teclistamab.6 The data were presented during an oral abstract session (Abstract #97).6 Additional pharmacokinetic data evaluating potential drug interactions with teclistamab were presented during a separate poster session (Abstract #3228), as well as analyses of serum teclistamab concentrations after intravenous and SC administration (Abstract #1911), to improve understanding of the clinical pharmacological profile of teclistamab.8,9 “Following the recent regulatory approval of teclistamab in the E.U. and U.S., we are encouraged by its potential to improve patient outcomes,” said Sen Zhuang, M.D., Ph.D., Vice President, Clinical Research and Development, Janssen Research & Development, LLC. “We remain committed to addressing the unmet needs of patients with multiple myeloma through off-the-shelf immunotherapies like teclistamab and where we can bring together novel therapeutic approaches in the treatment of complex blood cancers.” About the MajesTEC-1 Study The multicohort, open-label, Phase 1/2 MajesTEC-1 study (Phase 1: NCT03145181; Phase 2: NCT04557098) evaluated the safety and efficacy of teclistamab in patients with relapsed or refractory multiple myeloma.7,10 Patients in the Phase 1 study had shown progression on or intolerance to all established therapies and those in the Phase 2 portion had received three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody (i.e., triple-class exposed).7,10 Patients (n=165; median age, 64) received a weekly SC injection of teclistamab (1.5 mg/kg, with step up dosing of 0.06 and 0.3mg/kg).11 About the MajesTEC-2 Study MajesTEC-2 (NCT04722146), is a Phase 1b, multicohort study to evaluate the safety and efficacy of teclistamab in combination with other anticancer therapies in adults with multiple myeloma.1,2 In the presented study cohort, patients were eligible for treatment if they had received one to three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.1,2 Patients (n=32) received weekly doses of teclistamab (0.72 mg/kg or 1.5 mg/kg, with step-up dosing) plus the approved schedules of daratumumab SC 1800 mg and lenalidomide 25 mg.1 Responses were investigator assessed using International Myeloma Working Group criteria, and AEs were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except for CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), which were graded per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.1 About Teclistamab          Teclistamab is an off-the-shelf (ready to use) bispecific antibody.1,3 Teclistamab, a SC injection, redirects T-cells through two cellular targets (BCMA and CD3) to activate the body’s immune system to fight the cancer.3,5 Teclistamab is currently being evaluated in several monotherapy and combination studies.2,7,12,13,14 Teclistamab received European Commission (EC) approval in August 2022.15 The application for conditional marketing authorisation was reviewed by the Committee for Medicinal Products for Human Use (CHMP) under an accelerated timetable to enable faster patient access to this medicine.15 This was also supported through the European Medicines Agency’s (EMA) PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients’ unmet medical needs.16 For further information on teclistamab, please see the Summary of Product Characteristics at: https://www.ema.europa.eu/en/documents/product-information/tecvayli-epar-product-information_en.pdf.  About daratumumab and daratumumab SC  Janssen is committed to exploring the potential of daratumumab for patients with multiple myeloma across the spectrum of the disease. Daratumumab has been approved in eight indications for multiple myeloma, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.17 In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialise daratumumab. Since launch, daratumumab has become a foundational therapy in the treatment of multiple myeloma, having been used in the treatment of more than 300,000 patients worldwide.18 Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma.17 Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.19 CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.17 Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death.17 Daratumumab may also have an effect on normal cells.17 Data across eight Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that daratumumab based regimens resulted in significant improvement in progress free survival and/or overall survival.20,21,22,23,24,25,26,27 For further information on daratumumab, please see the Summary of Product Characteristics at: https://www.ema.europa.eu/en/documents/product-information/darzalex-epar-product-information_en.pdf.  About Multiple Myeloma  Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.28,29 In multiple myeloma, these malignant plasma cells change and grow out of control.28 In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,400 patients died.30 While some patients with multiple myeloma initially have no symptoms, others can have common symptoms of the disease which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels or kidney failure.31 About the Janssen Pharmaceutical Companies of Johnson & Johnson  At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism, & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension. Learn more at www.janssen.com/emea. Follow us at www.twitter.com/janssenEMEA for our latest news. Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Research & Development, LLC, and Janssen Biotech, Inc., are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.  †Dr. Searle has served as a consultant to Janssen; she has not been paid for any media work. 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 TECVAYLI®▼(teclistamab) and DARZALEX® (daratumumab). 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 materialize, actual results could vary materially from the expectations and projections of Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Research & Development, LLC, Janssen Biotech, Inc., any of the other Janssen Pharmaceutical Companies 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; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior 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 January 2, 2022, 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 www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. References: 1 Searle E, et al. Teclistamab in Combination with Subcutaneous Daratumumab and Lenalidomide in Patients with Multiple Myeloma: Results from One Cohort of MajesTEC-2, a Phase1b, Multicohort Study. American Society of Hematology Meeting 2022. December 2022.2 ClinicalTrials.gov. A Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma (MajesTEC-2). Available at: https://clinicaltrials.gov/ct2/show/NCT04722146. Last accessed: December 2022.3 European Medicines Agency. TECVAYLI Summary of Product Characteristics, October 2022. Available at: https://www.ema.europa.eu/en/documents/product-information/tecvayli-epar-product-information_en.pdf. Last accessed: December 2022.4 ClinicalTrials.gov. A Study to Compare Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) in Participants With Newly Diagnosed Multiple Myeloma (MajesTEC-7). Available at: https://clinicaltrials.gov/ct2/show/NCT05552222. Last accessed: December 2022.5Searle E, et al. Teclistamab in Combination with Subcutaneous Daratumumab and Lenalidomide in Patients with Multiple Myeloma: Results from One Cohort of MajesTEC-2, a Phase1b, Multicohort Study. American Society of Hematology Meeting 2022. Abstract #160. December 2022. 6 Nooka AK, et al. Teclistamab, a B-cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Correlative Analyses from MajesTEC-1. American Society of Hematology Meeting 2022. December 2022.7 ClinicalTrials.gov. A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1). Available at: https://clinicaltrials.gov/ct2/show/NCT04557098. Last accessed: December 2022.8 Willemin ME, et al. Drug Interaction Potential As a Result of Cytokine Release Syndrome Using a Physiologically Based Pharmacokinetic Model: Case Study of Teclistamab. American Society of Hematology Meeting 2022. December 2022.9 Miao X, et al. Teclistamab Population Pharmacokinetics and Exposure-Response Relationship Support 1.5 Mg/Kg Dose Regimen in Relapsed/Refractory Multiple Myeloma. American Society of Hematology Meeting 2022. December 2022.10 ClinicalTrials.gov. Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1). Available at: https://clinicaltrials.gov/ct2/show/NCT03145181. Last accessed: December 2022.11 Moreau P, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022 August;387:495-505.12 ClinicalTrials.gov. A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma. Available at: https://clinicaltrials.gov/ct2/show/NCT04586426. Last accessed:  December 2022.13 ClinicalTrials.gov. A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma. Available at: https://clinicaltrials.gov/ct2/show/NCT04108195. Last accessed: December 2022.14 ClinicalTrials.gov. A Study of Teclistamab in Combination With Daratumumab Subcutaneously (SC) (TecDara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-3). Available at: https://clinicaltrials.gov/ct2/show/NCT05083169. Last accessed: December 2022.15 European Medicines Agency. Accelerated assessment. Available at: https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/accelerated-assessment. Last accessed: December 2022.16 European Medicines Agency. PRIME Factsheet. Available at: https://www.ema.europa.eu/en/human-regulatory/research-development/prime-priority-medicines. Last accessed: December 2022.17 European Medicines Agency. DARZALEX summary of product characteristics, July 2022. Available at: https://www.ema.europa.eu/en/documents/product-information/darzalex-epar-product-information_en.pdf. Last accessed: December 2022.18 Janssen [data on file]. Number of patients treated with DARZALEX worldwide as of June 2022. RF-234772.19 Janssen EMEA. European Commission Grants Marketing Authorisation for DARZALEX®▼(Daratumumab) Subcutaneous Formulation for All Currently Approved Daratumumab Intravenous Formulation Indications. Available at: www.businesswire.com/news/home/20200604005487/en/European-Commission-GrantsMarketingAuthorisation-for-DARZALEX%C2%AE%E2%96%BC-daratumumab-SubcutaneousFormulation-for-all-CurrentlyApproved-Daratumumab-Intravenous-Formulation-Indications. Last accessed: December 2022.20 Moreau P, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, openlabel, phase 3 study. Lancet. 2019 Jul 6;394(10192):29-38.21 Facon T, et al. MAIA Trial Investigators. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019 May;380(22):2104-2115.22 Mateos MV, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. The Lancet. 2020 Jan 11;395 (10218):P132-141.23 Dimopoulos MA, et al. APOLLO Trial Investigators. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jun;22(6):801-812.24 Palladini G, et al. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood. 2020 Jul; 136(1):71-80.25 Chari A, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017 Aug;130(8):974-981.26 Bahlis NJ, et al. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia. 2020 Jul;34(7):1875-1884.27 Mateos MV, et al. Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR. Clin Lymphoma Myeloma Leuk. 2020 Aug;20(8):509-518.28 American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction Last accessed: December 2022.29 Abdi J et al. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms Oncotarget. 2013;4:2186–2207.30 GLOBOCAN 2020. Cancer Today Population Factsheets: Europe Region. Available at: https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf. Last accessed: December 2022.31 American Cancer Society. Multiple myeloma: early detection, diagnosis and staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf. Last accessed: December 2022. CP-361725December 2022 CONTACT: Media Enquiries:
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