Novel combination of TALVEY®▼ (talquetamab) and TECVAYLI®▼ (teclistamab) suggest high response rates and durable responses in triple-class refractory patients with relapsed or refractory multiple myeloma, including those with extramedullary disease

Data from the investigational Phase 1b RedirecTT-1 study demonstrate a safety profile consistent to talquetamab and teclistamab monotherapies¹

BEERSE, BELGIUM, Sept. 27, 2024 (GLOBE NEWSWIRE) — Janssen-Cilag International NV, a Johnson & Johnson company, today announced updated results from the investigational Phase 1b RedirecTT-1 study evaluating the first bispecific antibody combination of TALVEY^®▼ (talquetamab), the first bispecific targeting GPRC5D approved in Europe,² and TECVAYLI^®▼ (teclistamab), the first BCMA-directed bispecific therapy approved in Europe.³ The updated data showed high response rates and durable responses, with a consistent safety profile to each monotherapy, in patients with relapsed or refractory multiple myeloma (RRMM) who were triple-class exposed, including those with extramedullary disease.¹ These data were featured in an oral presentation at the 2024 International Myeloma Society (IMS) Annual Meeting, taking place in Rio de Janeiro, Brazil, from 25-28 September (Abstract #OA – 03).¹

“As multiple myeloma progresses, it becomes more difficult to treat, especially in patients with extramedullary disease, which spreads beyond the bone marrow and typically becomes resistant to standard therapies,” said Yael Cohen, M.D., Head of Myeloma Unit, Hematology Institute, Tel Aviv Sourasky Medical Center, Israel, and principal study investigator.* “These results reflected promising efficacy and a manageable safety profile for this combination of two innovative bispecific therapies and provides a potentially promising off-the-shelf option for patients with advanced multiple myeloma.”

At data cutoff, 44 patients had been treated with the recommended phase 2 regimen (RP2R) of 0.8 mg/kg of talquetamab in combination with 3 mg/kg of teclistamab every other week.¹ The overall response rate (ORR) was 79.5 percent, with a complete response or better (CR+) rate of 52.3 percent, an 18-month duration of response (DOR) of 85.9 percent, and an 18-month progression-free survival (PFS) rate of 69.8 percent with median follow-up of 18.2 months.¹

“Every person’s experience with multiple myeloma is unique and there is no one-size-fits-all treatment approach for this complex disease,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead in Haematology, Innovative Medicine, Johnson & Johnson. “Results from the RedirecTT-1 study are very promising and we remain focused on maximising the potential of our portfolio through innovative combination regimens, such as teclistamab plus talquetamab, to reshape care for patients.”

Results from a subgroup analysis of patients with extramedullary disease (EMD; ≥1 bone-independent lesion of ≥2 cm), a patient population often facing limited treatment options, demonstrated meaningful ORR and DOR for bispecific antibody-based treatment.¹ At the RP2R (n=18), results showed an ORR of 61.1 percent, with CR+ rate of 33.3 percent, an 18-month DOR of 81.8 percent, and an 18-month PFS rate of 52.9 percent in patients with EMD at median follow-up of 13.6 months.¹

The combination of talquetamab and teclistamab had a safety profile that was consistent with the known safety profiles of each agent as monotherapy.¹ Cumulative incidence of Grade 3/4 infections was slightly higher than that seen with either agent as monotherapy but plateaued from six months, and non-haematologic adverse events were generally low grade, including taste (50 percent) and non-rash skin (56.8 percent) and nail (47.7 percent) AEs.¹

“Talquetamab and teclistamab have already demonstrated efficacy as standalone bispecifics in the clinical and real-world settings,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Innovative Medicine, Johnson & Johnson. “We continue to research this innovative combination, as this study demonstrates both the efficacy and manageable safety profile of this combination, particularly in hard-to-treat patients such as those with EMD, as well as the combinability of talquetamab with other effective therapies.”

Additional data underscoring the combinability of talquetamab from the TRIMM-2 study will also be presented at IMS.⁴ First results from the RedirecTT-1 study were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

About the RedirecTT-1 Study
The RedirecTT-1 (NCT04586426) study is an ongoing Phase 1b dose escalation study of the combination of the bispecific T cell redirection antibodies talquetamab and teclistamab in patients (n=208) with RRMM.⁵ The primary objective is to identify the recommended Phase 2 regimens (RP2R(s)) and schedule for the study treatment and to characterise the safety of the RP2R(s) for the study treatment.²

In part 1, patients will receive talquetamab and teclistamab with or without daratumumab in 28-day cycles following initial step-up doses.² In part 2, patients will receive treatment doses (combination of talquetamab and teclistamab and daratumumab + talquetamab + teclistamab regimens) which will be determined by the RP2R[s] of the study treatment identified in Part 1.² In part 3, patients will receive talquetamab + teclistamab combination therapy, at the RP2R selected from Part 1 and Part 2.²

About Teclistamab
Teclistamab is an off-the-shelf (or ready to use) bispecific antibody.⁶ 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.^6,7,8,9,10

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.¹¹ 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.¹² To date, over 9000 patients have been treated with teclistamab worldwide.¹³

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 European Medicine Agency (EMA) regulations for new medicines and those given conditional approval, teclistamab is subject to additional monitoring.

About Talquetamab 
Talquetamab received conditional marketing authorisation (CMA) from the EC in August 2023, as monotherapy for the treatment of adult 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.¹⁴ The U.S. FDA also granted talquetamab approval in August 2023, for the treatment of adult patients with RRMM who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.¹⁵

Talquetamab is a bispecific T cell engaging antibody that binds to CD3 on T cells, and GPRC5D, a novel target which is highly expressed on the surface of multiple myeloma cells, with minimal to no expression detected on B-cells or B-cell precursors.⁵ To date, over 2,000 patients have been treated with talquetamab worldwide.¹⁶

For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using talquetamab, please refer to the Summary of Product Characteristics. In line with the EMA’s regulations for new medicines and those given conditional approval, talquetamab is subject to additional monitoring. 

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 talquetamab. 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.

*Dr. Yael Cohen, Head of Myeloma Unit, Hematology Institute, Tel Aviv Sourasky Medical Center, has provided consulting, advisory, and speaking services to Johnson & Johnson; she has not been paid for any media work. 

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¹ Cohen, Y., et al. Talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma: Updated phase 1b results from RedirecTT-1 with >1 year of follow-up. Abstract #OA – 03. IMS 2024. September 27, 2024.
² Monique C., Minnema, et al. Efficacy and safety of talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): Updated results from MonumenTAL-1. JCO 40, 8015-8015(2022).
³ Hua, G., Scanlan, R., Straining, R. and Carlson, D.S. (2023). Teclistamab-cqyv: The First Bispecific T-Cell Engager Antibody for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma. Journal of the advanced practitioner in oncology, 14(2), pp.163–171.
⁴ Bahlis, N., et al. Talquetamab + daratumumab + pomalidomide in patients with relapsed/refractory multiple myeloma: Results from the phase 1b TRIMM-2 study. IMS 2024. September 27, 2024.
⁵ ClinicalTrial.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?term=RedirecTT-1&draw=2&rank=1. Last accessed: September 2024.
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: September 2024.
⁷ 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: September 2024.
⁸ 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: September 2024.
⁹ 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: September 2024.
¹⁰ 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: September 2024.
¹¹ 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: September 2024.
¹² 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: September 2024.
¹³ Data on File. RF-432341. September 2024.
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¹⁵ FDA. FDA grants accelerated approval to talquetamab-tgvs for relapsed or refractory multiple myeloma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-talquetamab-tgvs-relapsed-or-refractory-multiple-myeloma. Last accessed: September 2024.
¹⁶ Data on File. RF-432343. September 2024.
¹⁷ American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction. Last accessed: September 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 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: September 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: September 2024.

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