On June 5, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that updated efficacy and safety results from the teclistamab Phase 1/2 MajesTEC-1 study.1 Teclistamab is an investigational, off-the-shelf, T-cell redirecting bispecific antibody targeting B-cell maturation antigen (BCMA), which is being studied in patients with relapsed or refractory multiple myeloma (RRMM) (Press release, Johnson & Johnson, JUN 5, 2022, View Source [SID1234615579]).1 The data were featured as part of an oral session during the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Applications seeking approval of teclistamab are currently under health authority review in the United States (U.S.) and Europe.
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The multicohort, open-label, Phase 1/2 MajesTEC-1 study is investigating the safety and efficacy of teclistamab in patients with RRMM who received at least three prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.3 As of March 2022, 165 patients were treated with teclistamab at the recommended subcutaneous (SC) Phase 2 dose (RP2D) of 1.5 mg/kg preceded by step-up doses of 0.06 mg/kg and 0.3 mg/kg across both Phase 1 (NCT03145181) and Phase 2 (NCT04557098) of the study.1
Longer Follow-up from MajesTEC-1 Study in Patients with Triple Class Exposed Multiple Myeloma (Abstract #8007)
At a median follow-up of 14.1 months (range, 0.26-24.4), an overall response rate (ORR) of 63 percent (95 percent Confidence Interval [CI], range, 55.2-70.4) was observed in patients with triple class exposed multiple myeloma, with a complete response (CR) or better achieved in 39.4 percent of patients.1 Study participants had three or more prior lines of therapy, with a median of five prior lines, including a prior proteasome inhibitor, immunomodulatory drug and anti-CD38 antibody.1 The majority of patients were triple-class refractory and/or refractory to their last line of treatment.1 Although response duration data are not mature, the median duration of response at this time is 18.4 months and has not been reached in patients who achieved a CR or better (95 percent CI, 14.9 not estimable).1 This suggests responses to teclistamab were durable and deepened over time.1 The medium progression-free survival (PFS) was 11.3 months (95 percent CI, 8.8–17.1).1 Adverse events (AEs) were low-grade for the most part and manageable with no new safety signals seen.1
These results from the MajesTEC-1 study were also simultaneously published online in The New England Journal of Medicine.2
"The longer term results from the MajesTEC-1 study suggest that patients are able to achieve deep and durable responses when treated with teclistamab," said Maria-Victoria Mateos, M.D., Ph.D., Consultant Physician in Haematology, University Hospital of Salamanca.* "These encouraging data reinforce the potential of teclistamab as a monotherapy for eligible patients with heavily pretreated multiple myeloma, in need of new treatment options."
No new safety signals were observed with longer follow-up.1 In 14.1 month follow-up data presented, the most common grade 3/4 haematologic AEs were neutropenia (64.2 percent); anaemia (37 percent); lymphopenia (32.7 percent) and thrombocytopenia (21.2 percent).1 Infections occurred in 76.4 percent of patients (44.8 percent grade 3/4).1 The most common nonhaematologic AE was cytokine release syndrome (CRS), all of which were grade 1/2 except for one transient grade 3 CRS (72.1 percent all grade).1 The median time to CRS onset was two days (range, 1-6) and median duration was two days (range, 1-9).1 There were five treatment-related deaths, and dose reductions and discontinuations due to AEs were infrequent.1
First Results from Cohort C of the MajesTEC-1 Study of Teclistamab in Patients with RRMM with Prior Exposure to BCMA Targeted Treatment (Abstract #8013)
Initial results were also presented from Cohort C of the MajesTEC-1 study evaluating teclistamab in the treatment of patients with RRMM who had previously been exposed to an anti-BCMA treatment.4 These patients had received a median of six prior lines of therapy, most (85 percent) were triple-class refractory and 35 percent were penta-drug refractory.4 The use of teclistamab following prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy and/or an antibody drug conjugate (ADC) (e.g., belantamab mafodotin) targeting BCMA resulted in a promising response rate in patients with heavily pretreated RRMM.4 At a median follow-up of 12.5 months (range, 0.7-14.4), the ORR was 52.5 percent (95 percent CI, 36.1-68.5) among 40 patients who received teclistamab in Cohort C.4 Responses to teclistamab occurred early and deepened over time, with comparable response rates in patients previously treated with an ADC and/or CAR-T.4
A tolerable side-effect profile was observed in patients previously treated with anti-BCMA treatment, with no dose reductions or discontinuations due to AEs.4 The safety profile for Cohort C was comparable with that observed in BCMA treatment-naive patients, with no new safety signals.4 In 12.5 month follow-up data, 26 patients (65 percent; 30 percent grade 3/4) had infections.4 The most common AEs (n=40) were CRS (65 percent any grade), with a median time to CRS onset and duration of two days (range, 2-6) and two days (range, 1-4) respectively.4 Cytopenias (grade 3/4) were noted as follows; neutropenia (62.5 percent); thrombocytopenia (30 percent); anaemia (35 percent); and lymphopenia (42.5 percent).4
"Patients with relapsed or refractory multiple myeloma have limited treatment options and only 30 percent will be able to achieve a response using conventional therapies," said Edmond Chan MBChB M.D. (Res), EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. "While unmet needs remain, we continue to be dedicated to developing innovative treatment approaches that improve outcomes for people living with multiple myeloma, at all stages of the disease."
Initial Patient-Reported Health-Related Quality of Life (HRQoL) Outcomes in Patients with RRMM Treated with Teclistamab (Abstract #8033)
Initial results from an analysis of patient-reported health-related quality of life (HRQoL) outcomes following treatment with teclistamab were also shared in a poster session.5 The study analysed patient-reported assessments of quality of life metrics among patients in the MajesTEC-1 trial who had received their first treatment dose by March 18, 2021.5 The metrics analysed include function (physical, role, emotional, cognitive, social); symptoms (fatigue, nausea/vomiting, pain, appetite loss, constipation, diarrhoea); and generic health (mobility, self-care, usual activities, pain/discomfort, anxiety/depression).5 Over 80 percent of the 110 patients included in the patient-reported outcomes (PRO) analysis noted meaningful improvement (percentages of patients with clinically meaningful change from baseline (EORTC QLQ-C30 scales: ≥10 points)) in at least one of the symptom scales.5 Reduction in pain scores occurred as early as cycle two.5 At the moment, no meaningful improvement was observed in the scales for physical functioning and fatigue.5 These initial PRO results complement recent clinical data and support teclistamab as a potential off-the-shelf, T-cell redirecting therapy for patients with RRMM.5
As of September 7, 2021, median duration of treatment was 5.7 months and median follow-up was 7.8 months.5 Global health status scores significantly improved from baseline (95 percent CIs for least squares mean change did not cross 0) at cycles four, six, and eight; emotional functioning significantly improved at all time points.5 PRO assessments included European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 item (EORTC QLQ-C30).5 PROs were assessed on day one of each treatment cycle (28 days per cycle).5 Additional follow-up is needed to assess the full benefit of meaningful improvement in functional outcomes.5
"The updated data presented at ASCO (Free ASCO Whitepaper) support the ongoing evaluation of teclistamab for the treatment of relapsed or refractory multiple myeloma," said Yusri Elsayed, M.D., M.HSc., Ph.D., Vice President, Disease Area Leader, Hematologic Malignancies, Janssen Research & Development, LLC. "These results underscore our ongoing commitment to address the unmet need for new therapeutic options and our effort to bring forward novel treatments for multiple myeloma patients in the near future."
#ENDS#
About Teclistamab
Teclistamab is an investigational, fully humanised IgG4, T-cell redirecting, bispecific antibody targeting both BCMA and CD3, on T-cells.1 BCMA is expressed at high levels on multiple myeloma cells.6,7,8,9,10 Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce killing of tumor cells.11
Teclistamab is currently being evaluated in several monotherapy and combination studies.3,12,13,14,15 In 2020, the European Commission (EC) and the U.S. Food and Drug Administration (FDA) each granted teclistamab Orphan Drug Designation for the treatment of multiple myeloma. In January 2021 and June 2021, teclistamab received a PRIority MEdicines (PRIME) designation by the European Medicines Agency (EMA) and Breakthrough Therapy Designation (BTD) by the FDA, respectively. PRIME offers enhanced interaction and early dialogue to optimise drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.16 The U.S. FDA grants BTD to expedite the development and regulatory review of an investigational 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 on at least one clinically significant endpoint over available therapy.17 In December 2021, Janssen submitted a Biologics License Application (BLA) to the FDA seeking approval of teclistamab for the treatment of patients with RRMM; a marketing authorisation application (MAA) was submitted to the EMA for teclistamab approval in January 2022.
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.18 In multiple myeloma, cancerous plasma cells change and grow out of control.18 In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,500 patients died.19 While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels or kidney failure.20