Initial Phase 1b study results show clinical activity with immune-based triplet therapy regimen (1)
BEERSE, Belgium, 10 December 2022 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today new results from a cohort of the Phase 1b MajesTEC-2 study of TECVAYLI®▼ (teclistamab), the first European Commission approved BCMAxCD3 bispecific T-cell engager antibody, in combination with DARZALEX® (daratumumab) subcutaneous (SC) formulation and lenalidomide.1,2,3 According to the results, the immune-based triplet therapy regimen had a manageable safety profile with no unexpected safety signals observed.1 A very good partial response (VGPR) or better was achieved by 90.3 percent of patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy, including a proteasome inhibitor and immunomodulatory drug, with responses deepening over time.1 These data were presented during the 2022 American Society of Hematology (ASH) Annual Meeting, taking place in New Orleans, U.S. (Abstract #160).1
“These results show the potential of the combination of the bispecific BCMA-directed antibody teclistamab with the anti-CD38 antibody daratumumab and lenalidomide in the treatment of patients with relapsed or refractory multiple myeloma,” said Emma Searle, M.D., Ph.D., Consultant Haematologist and Honorary Senior Lecturer, The Christie Hospital and University of Manchester, England, and study investigator.† “This is the first presentation of data from a teclistamab-based triplet regimen, and we are eager to better understand how this combination may benefit patients through ongoing clinical studies.”
At a median follow-up of 8.4 months (range, 1.1-12.9), the overall response rate (ORR) was 93.5 percent.1 Among all patients in the trial, VGPRs or better were achieved by 90.3 percent of patients, and 54.8 percent of patients achieved a complete response (CR) or better.1 Median time to response was one month (range, 0.7-3.3). The median time to CR or better was three months (range, 1.0-10.4).1 At data cut-off, 80.6 percent of patients remained progression-free and on treatment.1 Responses deepened over time, and median duration of response had not been reached.1
“Multiple myeloma is a complex disease and despite treatment advances in recent years, remains incurable. Our goal is to improve and expand on the options currently available to patients, in this area of high unmet medical need,” said Edmond Chan, MBChB M.D. (Res), EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. “The data presented at ASH indicate the potential of this combination regimen for people living with multiple myeloma who are in need of new treatment options, and aligns with our vision of tackling the disease with novel, complementary and combinable options across the disease continuum. We are committed to investigating this regimen further.”
MajesTEC-2 (NCT04722146) is a multicohort study.1,2 The primary objective of this cohort was to understand if the immunomodulatory effects of daratumumab SC and lenalidomide may enhance the function of teclistamab, potentially resulting in enhanced antimyeloma activity in a broader population of patients than currently indicated for.1,2 The MajesTEC-7 study (NCT05552222) will examine the potential of this combination compared to the combination of daratumumab, lenalidomide and dexamethasone, in patients with newly diagnosed multiple myeloma.4
The most frequent haematological adverse events (AEs) observed in the study included neutropenia (84.4 percent any grade, 78.1 percent grade 3/4) and thrombocytopenia (25 percent any grade, 15.6 percent grade 3/4).1 The most frequent non-haematological AE was cytokine release syndrome (CRS) (81.3 percent, all grade 1/2); 97 percent of CRS events occurred during cycle 1.1
Other common non-haematological AEs included fatigue (46.9 percent any grade, 6.3 percent grade 3/4); diarrhoea (46.9 percent any grade, none grade 3/4); cough (40.6 percent any grade, 3.1 percent grade 3/4); COVID-19 (37.5 percent any grade, 12.5 percent grade 3/4); insomnia (37.5 percent any grade, 3.1 percent grade 3/4); hypophosphataemia (31.3 percent any grade, 6.3 percent grade 3/4); pyrexia (31.3 percent any grade, 3.1 percent grade 3/4); upper respiratory tract infection (31.3 percent any grade, none grade 3/4); nausea (31.3 percent any grade, none grade 3/4); increased alanine aminotransferase (ALT) (28.1 percent any grade, 9.4 percent grade 3/4) and pneumonia (25 percent any grade, 15.6 percent grade 3/4).1 Two patients discontinued therapy due to an AE (COVID-19),1 considered to be unrelated to the study by investigator assessment.5 Infections were common among patients in the study and the majority were low grade (90.6 percent any grade, 37.5 percent grade 3/4).1
New Data from the Phase 1/2 MajesTEC-1 Study Evaluating Teclistamab in Relapsed or Refractory Multiple Myeloma Patients
New correlative analyses were also presented from the MajesTEC-1 study (NCT04557098).6,7 Data from these analyses may be used to help better understand baseline immune and tumour correlatives associated with outcomes in patients treated with teclistamab.6 The data were presented during an oral abstract session (Abstract #97).6 Additional pharmacokinetic data evaluating potential drug interactions with teclistamab were presented during a separate poster session (Abstract #3228), as well as analyses of serum teclistamab concentrations after intravenous and SC administration (Abstract #1911), to improve understanding of the clinical pharmacological profile of teclistamab.8,9
"Following the recent regulatory approval of teclistamab in the E.U. and U.S., we are encouraged by its potential to improve patient outcomes,” said Sen Zhuang, M.D., Ph.D., Vice President, Clinical Research and Development, Janssen Research & Development, LLC. “We remain committed to addressing the unmet needs of patients with multiple myeloma through off-the-shelf immunotherapies like teclistamab and where we can bring together novel therapeutic approaches in the treatment of complex blood cancers.”
References
1 Searle E, et al. Teclistamab in Combination with Subcutaneous Daratumumab and Lenalidomide in Patients with Multiple Myeloma: Results from One Cohort of MajesTEC-2, a Phase1b, Multicohort Study. American Society of Hematology Meeting 2022. December 2022.
4 ClinicalTrials.gov. A Study to Compare Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) in Participants With Newly Diagnosed Multiple Myeloma (MajesTEC-7). Available at: https://clinicaltrials.gov/ct2/show/NCT05552222. Last accessed: December 2022.
5 Searle E, et al. Teclistamab in Combination with Subcutaneous Daratumumab and Lenalidomide in Patients with Multiple Myeloma: Results from One Cohort of MajesTEC-2, a Phase1b, Multicohort Study. American Society of Hematology Meeting 2022. Abstract #160. December 2022.
6 Nooka AK, et al. Teclistamab, a B-cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Correlative Analyses from MajesTEC-1. American Society of Hematology Meeting 2022. December 2022.
8 Willemin ME, et al. Drug Interaction Potential As a Result of Cytokine Release Syndrome Using a Physiologically Based Pharmacokinetic Model: Case Study of Teclistamab. American Society of Hematology Meeting 2022. December 2022.
9 Miao X, et al. Teclistamab Population Pharmacokinetics and Exposure-Response Relationship Support 1.5 Mg/Kg Dose Regimen in Relapsed/Refractory Multiple Myeloma. American Society of Hematology Meeting 2022. December 2022.
10 ClinicalTrials.gov. Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multipl
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