Teclistamab and daratumumab subcutaneous (SC) combination led to a statistically significant progression-free survival and overall survival advantage compared to standard treatment after three years of follow-up1
Combination regimen granted Breakthrough Therapy Designation by U.S. FDA
BEERSE, BELGIUM, Dec. 09, 2025 (GLOBE NEWSWIRE) -- Johnson & Johnson today announced new data from the investigational Phase 3 MajesTEC-3 study that demonstrate the potential of TECVAYLI®▼ (teclistamab) plus DARZALEX® subcutaneous (daratumumab SC) formulation as early as second line for patients with relapsed/refractory multiple myeloma (RRMM).1 Results show an 83.4 percent reduction in the risk of disease progression or death compared to standard regimens at nearly three years follow-up (hazard ratio [HR], 0.17; 95 percent confidence interval [CI], 0.12-0.23; P<0.0001).1,2 More than 90 percent of patients who were progression-free at six months (n=249) remained progression-free at three years.1
The study evaluated the efficacy and safety of the investigational immunotherapy combination of teclistamab plus daratumumab SC versus daratumumab SC and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients with RRMM who have received 1-3 prior lines of therapy.1 The data were presented as a late-breaking oral presentation and in the press programme at the 2025 American Society of Hematology (ASH) Annual Meeting, with simultaneous publication in The New England Journal of Medicine.1,2
“The combination of teclistamab and daratumumab SC offers remarkable efficacy and safety consistent with their known profiles, and, alongside robust infection management protocols, an opportunity to improve patient outcomes across academic and community settings. It has the potential to change the standard of care as a steroid-sparing combination regimen suited for outpatient administration on the familiar daratumumab SC schedule,” said Maria-Victoria Mateos, M.D., Ph.D., Consultant Physician in Hematology, University Hospital of Salamanca.* “Teclistamab and daratumumab SC work in a complementary manner by targeting both BCMA and CD38 to prime and activate the immune system. The combination has shown to extend progression-free survival and overall survival versus standard of care as early as second line.”
Significant improvements compared to standard of care were observed across key secondary endpoints, including response rates, minimal residual disease (MRD)-negativity, overall survival (OS), and time to worsening of symptoms – revealing the comprehensive impact of the combination across varied patient measures.1 Teclistamab plus daratumumab SC achieved significantly higher overall response rates (89.0 percent vs. 75.3 percent; 95 percent CI, 1.68-4.18; P<0.0001) as well as complete response or better (≥CR) (81.8 percent vs. 32.1 percent; 95 percent CI, 6.47-14.14; P<0.0001).1 Rates of MRD-negativity at ≥CR 10-5 among the evaluable population were 89.3 percent versus 63.0 percent (odds ratio [OR], 5.01; P<0.0001) and at ≥CR 10-6 were 87.5 percent versus 41.8 percent (OR, 9.61; P<0.0001) compared to standard of care at nearly three years follow-up.1,2 OS favoured teclistamab plus daratumumab SC (HR, 0.46; 95 percent CI, 0.32-0.65; P<0.0001) across all prespecified subgroups.1 At three years, OS rates were 83.3 percent and 65.0 percent respectively.1 Additionally, patients experienced fewer symptoms for twice as long with teclistamab plus daratumumab SC versus standard of care, underscoring a significant improvement in patient-reported quality of life outcomes.1
“Daratumumab-based regimens have played a defining role in advancing how multiple myeloma is treated. The MajesTEC-3 study builds on that legacy by evaluating the impact of an off-the-shelf combination of the bispecific antibody teclistamab with daratumumab earlier in the treatment pathway,” said Ester in ‘t Groen, EMEA Therapeutic Area Head Haematology, Johnson & Johnson Innovative Medicine. “The unprecedented results we’re seeing reflect our commitment to get in front of cancer, strengthening evidence on how the novel combination of teclistamab and daratumumab SC could broaden effective options for people living with relapsed/refractory multiple myeloma as early as second line, where the medical need for durable outcomes remains high.”
In the study, teclistamab plus daratumumab SC and standard of care comparators had similar rates of Grade 3/4 (95.1 percent vs. 96.6 percent) treatment-emergent adverse events (TEAE).1 Most common Grade 3/4 events were cytopenia and infection.1 Infections were observed with teclistamab and daratumumab SC (any grade, 96.5 percent; Grade 3/4, 54.1 percent) and DPd/DVd comparator (any grade, 84.1 percent; Grade 3/4, 43.4 percent).1 Grade 3 or higher infections with teclistamab and daratumumab SC declined after the after six months of treatment with use of established immunoglobulin supplementation and infection prophylaxis protocols, along with switch to monthly dosing.1 Cytokine release syndrome occurred in 60.1 percent of patients treated with teclistamab plus daratumumab SC; all cases were Grade 1/2, did not lead to treatment discontinuation and were effectively managed using standard guidelines.1 Immune effector cell-associated neurotoxicity syndrome was rare and occurred in 1.1 percent of patients.1 Serious adverse events occurred in 70.7 percent of patients compared to 62.4 percent of patients treated with the comparator regimen, while treatment discontinuations due to adverse events were low (4.6 percent vs. 5.5 percent).1 Similar rates of deaths due to adverse events were observed with teclistamab and daratumumab SC and DPd/DVd comparator (7.1 percent vs. 5.9 percent).1
"With these data, we are entering a new era in treating multiple myeloma with the first immunotherapy combination to demonstrate superior overall survival as early as second line versus standard of care,” said Sen Zhuang, M.D., Vice President, Oncology Clinical Research, Johnson & Johnson Innovative Medicine. “With teclistamab plus daratumumab SC once again we have the potential to set a new standard of care for this disease. We continue to explore how regimens with our bispecifics portfolio can redefine the future for patients.”
Based on these results, Johnson & Johnson is working with regulatory bodies globally to bring the benefits of this combination regimen to eligible patients as quickly as possible. The Company has submitted a supplemental Biologics License Application (sBLA) for the use of teclistamab and daratumumab SC in combination as a treatment for RRMM to the U.S. Food and Drug Administration (FDA). The FDA has granted Breakthrough Therapy Designation (BTD) for the combination regimen; BTD is granted to expedite the development and regulatory review of a medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement over available therapies on a clinically significant endpoint(s).
The sBLA is being reviewed through the Real-Time Oncology Review (RTOR) programme, which enables the agency to initiate their evaluation of the data before the full application is formally submitted. An application has also been submitted to Brazil’s health agency, ANVISA (Agência Nacional de Vigilância Sanitária).
About the MajesTEC-3 Study
MajesTEC-3 (NCT05083169) is an ongoing, Phase 3 randomised study evaluating the safety and efficacy of teclistamab plus daratumumab subcutaneous (SC) (n=291) versus investigator’s choice of daratumumab subcutaneous (SC) and dexamethasone with either pomalidomide or bortezomib (n=296) (DPd/DVd) in patients with relapsed/refractory multiple myeloma (RRMM) who have received 1–3 prior lines of therapy.1,3 The primary endpoint is progression-free survival (PFS) and secondary endpoints include complete response or better (≥CR), overall response rate (ORR), minimal residual disease (MRD) negativity (10⁻⁵ by next-generation sequencing), overall survival (OS), time to worsening of symptoms (MySIm-Q), and safety.3 The MajesTEC-3 study is a part of the MajesTEC clinical programme, which includes exploring the potential of teclistamab as a combination regimen.3
About Teclistamab
Teclistamab received European Commission (EC) approval in August 2022 for the treatment of patients with RRMM who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy.4 In August 2023, the EC approved a Type II variation application for teclistamab, providing the option for a reduced dosing frequency of 1.5mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months.5
Teclistamab is an off-the-shelf (or ready-to-use) bispecific antibody.6,7 Teclistamab, a subcutaneous injection, redirects T-cells through two cellular targets (BCMA and CD3) to activate the body’s immune system to fight cancer. Teclistamab is currently being evaluated in several combination studies.3,6,8,9,10
For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using teclistamab, please refer to the Summary of Product Characteristics.▼In line with EMA regulations for new medicines and those given conditional approval, teclistamab is subject to additional monitoring.6
About Daratumumab and Daratumumab SC
Johnson & Johnson is committed to exploring the potential of daratumumab for patients with multiple myeloma across the spectrum of the disease.
In August 2012, Janssen Biotech, Inc., a Johnson & Johnson company, and Genmab A/S entered a worldwide agreement, which granted Johnson & Johnson an exclusive licence 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 618,000 patients worldwide.11 Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma.12 Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.12
CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.12 Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death.12 Daratumumab may also have an effect on normal cells.12 Data across ten Phase 3 clinical trials, in both the frontline and relapsed settings across all newly diagnosed multiple myeloma patients, have shown that daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival.13,14,15,16,17,18,19,20,21,22
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 currently an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.23,24 In multiple myeloma, these malignant plasma cells continue to proliferate, accumulating in the body and crowding out normal blood cells, as well as often causing bone destruction and other serious complications.23,24 In the European Union, it is estimated that more than 35,000 people were diagnosed with multiple myeloma in 2022, and more than 22,700 patients died.25 Patients living with multiple myeloma experience relapses which become more frequent with each line of therapy while remissions become progressively shorter.26,27,28 Whilst some patients with multiple myeloma initially have no symptoms, others can have common signs and symptoms of the disease, which can include bone fracture or pain, low red blood cell counts, fatigue, high calcium levels, infections, or kidney damage.29
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.
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 teclistamab and 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 materialise, actual results could vary materially from the expectations and projections of 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 most recent Annual Report on Form 10-K, 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 http://www.sec.gov/, http://www.jnj.com/ or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.
*Maria-Victoria Mateos, M.D., Ph.D., Consultant Physician in Hematology, University Hospital of Salamanca, has provided consulting, advisory, and speaking services to Johnson & Johnson; she has not been paid for any media work.
1 Mateos MV, et al. Phase 3 Randomized Study of Teclistamab plus Daratumumab Versus Investigator’s Choice of Daratumumab and Dexamethasone with either Pomalidomide or Bortezomib (DPd/DVd) in patients (pts) with Relapsed Refractory Multiple Myeloma (RRMM): Results of the MajesTEC-3 Study. Oral Presentation #06. American Society of Hematology (ASH) Annual Meeting; 06-09 December, 2025.
2 Costa L, et al. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. The New England Journal of Medicine. 2025; Full article and supplementary material. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2514663. Last accessed: December 2025.
3 ClinicalTrials.gov. A Study of Teclistamab in Combination With Daratumumab Subcutaneously (SC) (Tec-Dara) 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/study/NCT05083169. Last accessed: December 2025.
4 Johnson & Johnson.com. Janssen Marks First Approval Worldwide for TECVAYLI®▼(teclistamab) with EC Authorisation of First-in-Class Bispecific Antibody for the Treatment of Patients with Multiple Myeloma. Available at: https://innovativemedicine.jnj.com/emea/janssen-marks-first-approval-worldwide-tecvaylirvteclistamab-ec-authorisation-first-class-bispecific. Last accessed: December 2025.
5 Johnson & Johnson.com. European Commission Approves Reduced Dosing Frequency for Janssen’s Bispecific Antibody TECVAYLI®▼ (teclistamab). Available at: https://www.jnj.com/media-center/press-releases/european-commission-approves-reduced-dosing-frequency-for-janssens-bispecific-antibody-tecvayli-teclistamab. Last accessed: December 2025.
6 European Medicines Agency. TECVAYLI Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/tecvayli-epar-product-information_en.pdf. Last accessed: December 2025.
7 Moreau P, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. New England Journal of Medicine. 2022;287(6):494-505.
8 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 2025.
9 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 2025.
10 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 2025.
11 J&J Data on File (RF-452129). Number of Patients Treated with DARZALEX Worldwide as of December 2024.
12 Janssen EMEA. European Commission Grants Marketing Authorisation for DARZALEX® (Daratumumab) Subcutaneous Formulation for All Currently Approved Daratumumab Intravenous Formulation Indications. Available at: http://www.businesswire.com/news/home/20200604005487/en/European-Commission-GrantsMarketingAuthorisation-for-DARZALEXpercentC2percentAEpercentE2percent96percentBC-daratumumab-SubcutaneousFormulation-for-all-CurrentlyApproved-Daratumumab-Intravenous-Formulation-Indications. Last accessed: December 2025.
13 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, Open-label, Phase 3 Study. Lancet. 2019;394(10192):29-38.
14 Facon T, et al. MAIA Trial Investigators. Daratumumab Plus Lenalidomide and Dexamethasone for Untreated Myeloma. New England Journal of Medicine. 2019;380(22):2104-2115.
15 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;395(10218):132-141.
16 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;22(6):801-812.
17 Palladini G, et al. Daratumumab Plus CyBorD for Patients with Newly Diagnosed AL Amyloidosis: Safety Run-in Results of ANDROMEDA. Blood. 2020;2;136(1):71-80.
18 Chari A, et al. Daratumumab Plus Pomalidomide and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma. Blood. 2017;130(8):974-981.
19 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;34(7):1875-1884.
20 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;20(8):509-518.
21Usmani S Z, et al. Daratumumab + Bortezomib/Lenalidomide/Dexamethasone in Patients with Transplant-Ineligible or Transplant-Deferred Newly Diagnosed Multiple Myeloma: Results of the Phase 3 CEPHEUS Study. Oral Presentation. 21st International Myeloma Society (IMS) Annual Meeting. September 25 – 28, 2024.
22 Sonneveld P, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. New England Journal of Medicine. 2024; 390(4):301-313.
23 Abdi J, et al. Drug Resistance in Multiple Myeloma: Latest Findings on Molecular Mechanisms. Oncotarget. 2013;4(12):2186-2207.
24 American Society of Clinical Oncology. Multiple Myeloma: Introduction. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/if-you-have-multiple-myeloma. Last accessed: December 2025.
25 ECIS - European Cancer Information System. Estimates of Cancer Incidence and Mortality in 2022, by Country. Multiple Myeloma. Available at: https://ecis.jrc.ec.europa.eu/explorer.php?$0-0$1-All$2-All$4-1,2$3-51$6-0,85$5-2022,2022$7-7$CEstByCountry$X0_8-3$X0_19-AE27$X0_20-No$CEstBySexByCountry$X1_8-3$X1_19-AE27$X1_-1-1$CEstByIndiByCountry$X2_8-3$X2_19-AE27$X2_20-No$CEstRelative$X3_8-3$X3_9-AE27$X3_19-AE27$CEstByCountryTable$X4_19-AE27. Last accessed: December 2025.
26 Bhatt P, et al. Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse. Curr Oncol. 2023;30(2):2322-2347.
27 Hernández-Rivas JÁ, et al. The Changing Landscape of Relapsed and/or Refractory Multiple Myeloma (MM): Fundamentals and Controversies. Biomark Res. 2022;10(1):1-23.
28 Gavriatopoulou M, et al. Metabolic Disorders in Multiple Myeloma. Int J Mol Sci. 2021;22(21):11430.
29 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 2025.
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CONTACT: Media contact: Jenni Mildon jmildon@its.jnj.com +44 7920 418 552 Investor contact: Lauren Johnson investor-relations@its.jnj.com
