Janssen Presents Longer-Term Data for TECVAYLI®▼ (teclistamab) Showing a Duration of Response of 22 Months in Patients with Relapsed or Refractory Multiple Myeloma

By GlobeNewswire On Jun 5, 2023

More than 60 percent of patients achieved an overall response and 45.5 percent of patients achieved a complete response or better by nearly five months¹

Additional data highlight deep and durable responses with biweekly teclistamab dosing and show potential strategies for improving cytokine release syndrome with prophylactic–tocilizumab^2,3

BEERSE, BELGIUM, June 05, 2023 (GLOBE NEWSWIRE) — The Janssen Pharmaceutical Companies of Johnson & Johnson announced today long-term data from the pivotal Phase 1/2 MajesTEC-1 study showing the sustained efficacy and safety of TECVAYLI^®▼ (teclistamab) in the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who were triple-class exposed and previously received treatment with three or more prior lines of therapy.¹ These results showed that nearly half of patients achieved a complete response (CR) or better which underscore the continued durable responses seen in this patient population.¹ These data were featured at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place in Chicago, from 2-6 June along with additional poster presentations from MajesTEC-1 featuring data on the durability of responses with teclistamab biweekly dosing as well as an evaluation of the use of tocilizumab, given prophylactically, to examine potential reduction of cytokine release syndrome (CRS) in the management of RRMM patients treated with teclistamab.²^,³

Extended follow-up data from the pivotal Phase 1/2 MajesTEC-1 study of teclistamab demonstrate an overall response rate (ORR) of 63 percent, with responses that continued to deepen over time.¹ More than 45 percent of patients have now achieved a CR or better, and median time to CR or better was 4.6 months (range, 1.6-18.5).¹ The minimal residual disease (MRD) negativity rate by Day 100 from first dose of teclistamab in evaluable patients was 81 percent.¹

Median duration of response was 22 months (95 percent Confidence Interval [CI], 16-not estimable [NE]) for all responders, and 27 months (95 percent CI, 22-NE) for patients who achieved a CR or better.¹ Median progression free survival (mPFS) was 11 months (95 percent CI, 9-16) for all patients, and was 27 months (95 percent CI, 23-NE) for patients who achieved a CR or better.¹ Median overall survival (OS) was 22 months (95 percent CI, 15-NE) for all patients and was not reached for patients who achieved a CR or better.¹

“After a median of two years’ follow up, it’s encouraging to see sustained and durable responses, particularly in such a difficult-to-treat population with such high unmet medical need,” said Niels van de Donk, M.D., Professor of Hematology at Amsterdam University Medical Centers, and principal study investigator.^† “This is the most robust data set to date for teclistamab, and our findings further support the role it can play in the treatment of patients with relapsed or refractory disease.”

The most common Grade 3/4 haematologic adverse events (AEs) were neutropenia (65.5 percent); anaemia (37.6 percent); lymphopenia (34.5 percent) and thrombocytopenia (22.4 percent).¹ Infections occurred in 80 percent of patients (55.2 percent Grade 3/4).¹ Incidence and severity of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) did not change during the long term follow-up period.¹^,⁴ As of data cut-off, AEs leading to dose reduction or discontinuation of teclistamab treatment were infrequent; there were seven treatment related deaths observed in the study.¹

Results Suggest Durable Responses with Biweekly Dosing of Teclistamab (Abstract #8034)

Results of an analysis of the investigational use of biweekly (Q2W) or monthly (Q4W) dosing of teclistamab in the MajesTEC-1 study were also presented, demonstrating sustained deep responses with less frequent dosing in responding patients.² Patients with relapsed or refractory disease who had received at least three prior lines of therapy including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody were initially treated with the recommended Phase 2 dose (RP2D) of 1.5 mg/kg teclistamab weekly (QW) administered subcutaneously and were able to switch to Q2W dosing if they achieved a confirmed partial response (PR) or better after four or more cycles of treatment (Phase 1), or a confirmed CR or better for six months or longer (Phase 2).² Patients could further switch to Q4W dosing if they demonstrated continued response on the Q2W schedule.² Patient responses were assessed per International Myeloma Working Group (IMWG) 2016 criteria.⁵

As of January 2023, 165 patients had received teclistamab at the RP2D.² Of 104 responders, 63 patients switched to Q2W and nine patients subsequently switched to Q4W dosing.² Results from the analysis showed that at the time of switch, 85.7 percent of patients had a response of a CR or better, 12.7 percent were in very good partial response (VGPR), and 1.6 percent were in PR.² The median time to switch from QW to Q2W dosing was 11.3 months (range, 3-30).² At a median follow-up of 12.6 months (range, 1-25) since switching, the median duration of response was not yet reached, and 68.7 percent (95 percent CI, 53.6-79.7) of patients who switched remained in response for two or more years from the time of first response.² As of data cut-off, 42 of 63 responders maintained a response after switching to less frequent dosing.² The new onset of Grade 3 or higher infections was lower in responders who switched to Q2W or Q4W dosing compared to those who remained on QW dosing (15.6 percent vs. 33.3 percent).²

These data have been submitted to health authorities globally as part of a regulatory application which, if approved, would allow appropriate patients to receive teclistamab biweekly.

“These data suggest less frequent dosing of teclistamab may be considered after achieving a response,” said Rachel Kobos, M.D., Vice President, Janssen Oncology Research & Development, LLC. “We remain committed to finding not only innovative treatments for patients in need of new options, but also new strategies for optimising regimens and reducing side effects during treatment.”

Evaluation of Prophylactic Tocilizumab for the Reduction of Cytokine Release Syndrome (Abstract #8033)

Important new data studying the investigational prophylactic use of tocilizumab (toci), an interleukin-6 receptor inhibitor, for the reduction of CRS in patients treated with teclistamab were also presented at the meeting.³ In this prospective exploratory cohort of MajesTEC-1, eligible adult patients with RRMM received subcutaneous teclistamab.³ Patients were prophylactically dosed with toci (a single 8 mg/kg intravenous [IV] dose) within four hours prior to the first teclistamab step-up dose, and CRS was graded per Lee Criteria and managed per institutional guidelines.³^,⁵^,⁶

Results of the study (n=23) showed that a single dose of toci before teclistamab treatment reduced the overall incidence of CRS relative to the MajesTEC-1 study, with no evidence of impact on response.³ At a median follow-up of 2.6 months (range, 0.1-7), CRS was 26 percent (all Grade 1 or 2), representing a 2.5 fold reduction in CRS versus the incidence seen in MajesTEC-1, in which prophylactic toci was not employed.³ Median time to onset of CRS was two days, with a median duration of two days.³ All CRS events were managed with toci (one added dexamethasone); all CRS events resolved and no patients discontinued teclistamab due to CRS.³

“The latest MajesTEC-1 data add to the growing body of evidence in support of the integral role of teclistamab in improving outcomes for patients with relapsed and refractory multiple myeloma,” said Edmond Chan, MBChB M.D. (Res), Senior Director EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. “With extended follow up of approximately two years, we are seeing that deep and durable responses are maintained, and based on the dosing cohort data, we may be able to offer patients and physicians greater flexibility, convenience, and reduced time in hospital, with a less frequent dosing schedule.”

#ENDS#

About the MajesTEC-1 Study
MajesTEC-1 (NCT03145181, NCT04557098), is a Phase 1/2 single-arm, open-label, multicohort, multicentre dose-escalation study to evaluate the safety and efficacy of teclistamab in adults with RRMM who received three or more prior lines of therapy.⁵^,⁷

Phase 1 of the study (NCT03145181) was conducted in two parts: dose escalation (Part 1) and dose expansion (Part 2).¹^,⁷ It evaluated safety, tolerability, pharmacokinetics, and preliminary efficacy of teclistamab in adult participants with RRMM.¹^,⁷ Study criteria for Phase 1 excluded patients who had Eastern Cooperative Oncology Group (ECOG) performance score of two or higher, known active central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma.¹^,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.¹^,⁵ During week one, participants received step-up doses of teclistamab subcutaneously (0.06 and 0.3 mg/kg).¹^,⁵ Subsequently, participants received weekly treatment doses of teclistamab subcutaneous 1.5 mg/kg until disease progression or unacceptable toxicity.¹^,⁵ Efficacy was established based on ORR as determined by the Independent Review Committee (IRC) assessment using IMWG 2016 criteria.¹^,⁵

The primary endpoint was ORR or unacceptable toxicity.¹^,⁵ Secondary endpoints included duration of response, VGPR, CR, stringent complete response, time to response, MRD status, PFS, OS, safety, pharmacokinetics, immunogenicity and patient-reported outcomes.¹^,⁵

As of January 2023, 165 patients in MajesTEC-1 study were treated with teclistamab at the recommended subcutaneous RP2D of 1.5 mg/kg preceded by step-up doses of 0.06 and 0.3 mg/kg with the option to switch to dosing once every two weeks (Q2W).¹ At the data cut-off, 47 patients remained in the study, and 42 of 47 had switched to Q2W dosing and maintained a response.¹

About Teclistamab
Teclistamab is an off-the-shelf (or ready to use) bispecific antibody.⁸ Teclistamab, a subcutaneous injection, redirects T-cells through two cellular targets (BCMA and CD3) to activate the body’s immune system to fight the cancer. Teclistamab is currently being evaluated in several monotherapy and combination studies.⁵^,⁷^,⁹^,¹⁰^,¹¹^,¹²

Teclistamab received European Commission (EC) approval in August 2022. 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.¹³ 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.¹⁴

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.

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.¹⁵^,¹⁶ In multiple myeloma, these malignant plasma cells change and grow out of control.¹⁵ In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,400 patients died.¹⁷ 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.¹⁸

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.linkedin.com/janssenEMEA for our latest news. Janssen Pharmaceutica NV, Janssen-Cilag Limited and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

†Niels van de Donk, M.D., has served as a paid consultant to Janssen; he has not been paid for any media work.

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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 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 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 January 1, 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 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 Van de Don N et al. Long-Term Follow-Up From MajesTEC-1 of Teclistamab, a BCMA×CD3 Bispecific Antibody, in Patients With Relapsed/Refractory Multiple Myeloma. Poster presentation (#8011) at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. June 2023.
² Usmani S et al. Durability of Responses With Biweekly Dosing of Teclistamab in Patients With Relapsed/Refractory Multiple Myeloma Achieving a Clinical Response in the MajesTEC-1 Study. Poster presentation (#8034) at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. June 2023.
³ Van de Donk N et al. Evaluation of prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (CRS) to inform the management of patients (pts) treated with teclistamab in MajesTEC-1. Poster presentation (#8033) at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. June 2023.
⁴ Moreau P et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022;387(6):495-505.
⁵ 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: June 2023.
⁶ Lee DW et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-95.
⁷ 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: June 2023.
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⁹ 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 2023.
¹⁰ 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 2023.
¹¹ 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 2023.
¹² 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 2023.
¹³ European Medicines Agency. Accelerated assessment. Available at: https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/accelerated-assessment. Last accessed: June 2023.
¹⁴ European Medicines Agency. PRIME Factsheet. Available at: https://www.ema.europa.eu/en/human-regulatory/research-development/prime-priority-medicines. Last accessed: June 2023.
¹⁵ American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction Last accessed: June 2023.
¹⁶ Abdi J et al. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms Oncotarget. 2013;4(12):2186–2207.
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June 2023

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