TECVAYLI®▼ (teclistamab) shows sustained deep and durable responses in patients with relapsed or refractory multiple myeloma

New MajesTEC-1 data show a median duration of response of 24 months, with responses deepening, including in patients who switched to biweekly dosing¹

Separate analyses from the MajesTEC-1 and OPTec studies are the first to underscore the opportunity for outpatient administration of teclistamab^2,3

Beerse, Belgium, June 03, 2024 (GLOBE NEWSWIRE) — Janssen-Cilag International NV, a Johnson & Johnson company today announced longer-term data from the pivotal Phase 1/2 MajesTEC-1 study of TECVAYLI^®▼ (teclistamab) showing deep and durable responses in patients with relapsed or refractory multiple myeloma (RRMM) who are triple-class exposed (TCE)^a and who previously received three or more prior lines of therapy, including in patients who switched to less frequent dosing (Abstract #7540).¹ These data were featured at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place in Chicago from 31 May-4 June, in a poster presentation.¹

Additional presentations highlight the potential for outpatient step-up administration with prophylactic tocilizumab from the MajesTEC-1 study (Abstract #7517) and Phase 2 OPTec study (Abstract #7528), as well as first results from the subgroup analysis of patients with high-risk (HR) features that will be presented at the 2024 European Hematology Association (EHA) Congress, taking place in Madrid from 13-16 June (Abstract #923).^2–4 The safety run-in MajesTEC-7 study in frontline teclistamab administration (Abstract #7506) will also be presented at ASCO.⁵

“With the longest follow-up of any bispecific antibody, teclistamab demonstrates continued deep and durable responses observed in patients with relapsed or refractory multiple myeloma who have limited treatment options,” said Niels van de Donk, M.D., Professor of Hematology at Amsterdam University Medical Centers, and principal study investigator.^† “The results of the MajesTEC-1 study indicate the potential of teclistamab to transform the treatment paradigm, and clinical studies are investigating whether teclistamab may be a pivotal advancement for improved care and management in the broader patient population.”

Results from the MajesTEC-1 study show that, at a median follow-up of 30.4 months, patients treated with teclistamab at the recommended Phase 2 dose (RP2D)^b (n=165) demonstrated an overall response rate (ORR) of 63 percent, with responses continuing to deepen and 46 percent of patients achieving a complete response (CR) or better.¹ For patients with a CR or better, mDOR, mPFS, and mOS were not yet reached, and estimated 30-month DOR, PFS, and OS rates were 61, 61 and 74 percent, respectively.¹ Patients who achieved a partial response or better after a minimum of four cycles of therapy (Phase 1), or maintained a CR or better for a minimum of six months (Phase 2) per protocol, had the option to switch to biweekly dosing (every two weeks) (Q2W).¹ Additionally, 37 out of 38 patients who switched to Q2W dosing maintained responses.¹

The safety profile remained consistent with a notable decrease in new onset of severe infections over time.¹ Adverse events (AEs) included neutropenia (any grade, 72 percent; grade 3/4, 66 percent), anaemia (any grade, 55 percent; grade 3/4, 38 percent), thrombocytopenia (any grade, 42 percent; grade 3/4, 23 percent), lymphopenia (any grade, 36 percent; grade 3/4, 35 percent), and infections (any grade, 79 percent; grade 3/4, 55 percent).¹ Of 22 grade 5 infections, 18 were due to COVID-19.¹ The decrease in new onset grade 3 or greater infections may be due to switching to Q2W dosing or other factors, such as implementing the use of intravenous immunoglobulin.¹

“These longer-term results continue to demonstrate the benefits of less frequent dosing of teclistamab, providing eligible patients a more tailored, less burdensome option, while still achieving deep and durable responses,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Johnson & Johnson Innovative Medicine. “Teclistamab is an important part of our multiple myeloma portfolio and highlights our commitment to providing transformational therapies as we strive towards our ultimate goal of curing multiple myeloma.”

Teclistamab studies investigate outpatient administration in patients with RRMM, examining a more convenient approach to treatment, including in a community setting

Extended follow-up of patients from a MajesTEC-1 cohort investigating the prophylactic use of tocilizumab for the reduction of cytokine release syndrome (CRS) in patients treated with teclistamab were also presented at ASCO, in an oral presentation (Abstract #7517).² Results show a single dose of tocilizumab before teclistamab in patients with RRMM (n=24) reduced the incidence of CRS versus the overall MajesTEC-1 population (n=165) with a 65 percent relative reduction (25 percent vs. 72 percent).² This approach is continuing to be evaluated in the Phase 2, multicentre, prospective OPTec study of teclistamab in the community setting, presented as a poster presentation (Abstract #7528) at ASCO.³ Data show preliminary evidence that prophylactic tocilizumab potentially reduces the incidence of CRS, with no new safety concerns to date and underscores the opportunity for outpatient administration.³

Evaluation of patients with high-risk multiple myeloma from MajesTEC-1 study shows clinical benefit from treatment with teclistamab

Subgroup analysis from the MajesTEC-1 study of teclistamab investigating patients with HR RRMM will be presented at EHA (Abstract #923).⁴ Results show at a median follow-up of 30 months, patients who were aged 75 years or older (n=24), patients who had HR cytogenetics (n=38) and patients who were penta-drug refractory (n=50) demonstrated similar efficacy as the overall RP2D population with an ORR of 54 percent, 61 percent and 60 percent and a CR or better rate of 42 percent, 42 percent, and 48 percent, respectively.⁴ The data demonstrate the clinical benefit of teclistamab as an additional treatment option for some patients with HR features who typically face poor outcomes.⁴ The safety profile across subgroups was consistent with the RP2D population, including overall incidence and severity of TEAEs.⁴

Data from a safety run-in cohort of the Phase 3 MajesTEC-7 study shows early clinical profile of teclistamab-based regimen in patients with transplant ineligible/not intended newly diagnosed multiple myeloma

The results, presented in an oral presentation (Abstract #7506) at ASCO, of the first safety run-in (SRI) cohort of the Phase 3 MajesTEC-7 study provide preliminary data for a teclistamab-based regimen in transplant ineligible/not intended newly diagnosed multiple myeloma.⁵ Patients (n=26) received teclistamab in combination with daratumumab and lenalidomide (DR).⁵ At a median follow-up of 13.8 months, the ORR was 92 percent, with 23 patients remaining on treatment.⁵ Treatment-emergent adverse events (TEAEs) occurred in 100 percent of patients, where 61.5 percent of patients experienced grade 1/2 CRS in cycle one – all of which resolved.⁵

“Over the past two years, teclistamab has helped over 10,000 patients with relapsed or refractory multiple myeloma,” said Rachel Kubos, M.D., Vice President, Oncology Research & Development, Johnson & Johnson Innovative Medicine. “Through robust clinical data and real-world evidence, and by leveraging our team’s expertise, we’re working relentlessly to address unmet needs for patients with myeloma and drive the development of new treatment options for use across the treatment paradigm, including in the frontline setting.”

About the MajesTEC-1 Study

MajesTEC-1 (NCT03145181, NCT04557098) is a Phase 1/2 single-arm, open-label, multicohort, multicentre dose-escalation study evaluating the safety and efficacy of teclistamab in adults with RRMM who received three or more prior lines of therapy.^6,7

Phase 1 of the study (NCT03145181) was conducted in two parts: dose escalation (Part 1) and dose expansion (Part 2).⁶ It evaluated safety, tolerability, pharmacokinetics, and preliminary efficacy of teclistamab in adult participants with RRMM.⁷ Phase 2 of the study (NCT04557098) evaluated the efficacy of teclistamab at the RP2D, established at subcutaneous 1.5 mg/kg weekly, as measured by ORR.⁶

About the OPTec Study

OPTec (NCT05972135) is a Phase 2, single-arm, non-randomised, multicentre, prospective study evaluating the use of prophylactic tocilizumab in patients with RRMM to reduce the incidence and severity of CRS associated with administration of the step-up dosing regimen of teclistamab in the outpatient setting.⁸

About the MajesTEC-7 Study

MajesTEC-7 (NCT05552222), is a Phase 3 randomised study, comparing teclistamab in combination with daratumumab SC and lenalidomide (Tec-DR) and talquetamab in combination with daratumumab SC and lenalidomide (Tal-DR) versus daratumumab SC, lenalidomide, and dexamethasone (DRd) in participants with newly diagnosed multiple myeloma who are either ineligible or not intended for autologous stem cell transplant as initial therapy.⁹

About Teclistamab

Teclistamab is an off-the-shelf (or ready to use) bispecific antibody.¹⁰ Teclistamab, a subcutaneous injection, redirects T-cells through two cellular targets (B-cell maturation antigen [BCMA] and CD3) to activate the body’s immune system to fight the cancer. Teclistamab is currently being evaluated in several combination studies. ^{10,11,12,13,14}

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.¹⁵ In August 2023, the EC approved a Type II variation application for TECVAYLI®▼ (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.¹⁶

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.¹⁰ In line with EMA regulations for new medicines and those given conditional approval, teclistamab is subject to additional monitoring.¹⁰

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.^17,18 In multiple myeloma, these malignant plasma cells change and grow out of control. 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.¹⁹ 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.²⁰

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.janssen.com/emea. Follow us at https://www.linkedin.com/company/jnj-innovative-medicine-emea. Janssen Pharmaceutica NV, Janssen-Cilag Limited, 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 teclistamab. 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 Pharmaceutica NV, Janssen-Cilag Limited, Janssen Research & Development, LLC 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 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 http://www.sec.gov/, http://www.jnj.com/ or on request from Johnson & Johnson. None of Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Research & Development, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

^‡ Niels van de Donk, M.D., Professor of Hematology at Amsterdam University Medical Centers, and principal study investigator has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.

^a Triple-class exposed (TCE): patients who have previously received an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody (mAb).
^b Recommended Phase 2 dose (RP2D): dose of a drug that was identified in a Phase 1 study (dose finding study).

¹ Garfall, A., et al. Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma. 2024 ASCO Annual Meeting – American Society of Clinical Oncology.
² Van de Donk, N, et al. Longer-term follow-up of patients (pts) receiving prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (CRS) in the phase 1/2 MajesTEC-1 study of teclistamab in relapsed/refractory multiple myeloma (RRMM). 2024 ASCO Annual Meeting – American Society of Clinical Oncology.
³ Rifkin, R., et al. OPTec: A phase 2 study to evaluate outpatient (OP) step-up administration of teclistamab (Tec), a BCMA-targeting bispecific antibody, in patients (pts) with relapsed/refractory multiple myeloma (RRMM). 2024 ASCO Annual Meeting – American Society of Clinical Oncology.
⁴ Costa, L, et al. Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma with high-risk features: A subgroup analysis from the phase 1/2 MajesTEC-1 study. 2024 EHA Hybrid Congress – European Hematology Association.
⁵ Touzeau, C, et al. Safety results from the phase 3 MajesTEC-7 study in patients (pts) with transplant ineligible/not intended newly diagnosed multiple myeloma (NDMM). 2024 ASCO Annual Meeting – American Society of Clinical Oncology.
⁶ A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1). Available at: https://clinicaltrials.gov/ct2/show/NCT04557098. Last accessed: June 2024.
⁷ 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: June 2024.
⁸ Outpatient Administration of Teclistamab for Multiple Myeloma. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05972135. Last accessed: June 2024.
⁹ A Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (Tal-DR) in Participants With Newly Diagnosed Multiple Myeloma (MajesTEC-7). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05552222. Last accessed: June 2024.
¹⁰ 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: June 2024.
¹¹ 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: June 2024.
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: June 2024.
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: June 2024.
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: June 2024.
¹⁵ Janssen.com. Janssen Marks First Approval Worldwide. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/teclistamab_ec_approval_release.pdf. Last accessed: June 2024.
¹⁶ Janssen.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: June 2024.
¹⁷ American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction. Last accessed: May 2024.
¹⁸ Abdi J, et al. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms Oncotarget. 2013;4(12):2186–2207.
¹⁹ 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: June 2024.
²⁰ 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: June 2024.

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June 2024

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