SUMMARY

• Janssen does not recommend any practices, procedures or usage that deviate from the product labeling or are not approved by the regulatory agencies.
• MajesTEC-2 (MMY1004) is an ongoing, phase 1b, multicohort study evaluating TECVAYLI in combination with other anticancer therapies in patients with multiple myeloma (MM). Cohort D is evaluating the efficacy and safety of TECVAYLI in combination with lenalidomide in patients with triple-class exposed MM who received ≥2 prior lines of therapy.^1,2
  • Tan et al (2023)² presented the efficacy and safety of TECVAYLI in combination with lenalidomide in 31 patients at a median follow-up of 10.8 months (range, 1.1-16.8).

CLINICAL DATA - majestec-2 study - cohort d

MajesTEC-2 (MMY1004; clinicaltrials.gov identifier: NCT04722146) is an ongoing, phase 1b, multicohort study evaluating the efficacy and safety of TECVAYLI in combination with other anticancer treatments in patients with MM.^1,2

• Cohort D is evaluating the efficacy and safety of TECVAYLI in combination with lenalidomide in 31 patients with triple-class exposed MM who received ≥2 prior lines of therapy.²

Study Design/Methods

• Key eligibility criteria: ≥18 years of age, documented MM per International Myeloma Working Group (IMWG) criteria, measurable MM, received ≥2 prior lines of treatment including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody.^1,2
• Key exclusion criteria: prior B-cell maturation antigen (BCMA) targeting treatment.¹
• Dosing: Eligible patients received oral (PO) doses of lenalidomide and subcutaneous (SC) doses of TECVAYLI, which included step-up dosing followed by once weekly (QW) treatment doses at 2 weight-based dose levels. The step-up doses were administered 2-4 days apart and completed 2-4 days prior to the first full treatment dose of TECVAYLI.²
  • Dose level 1:
    • TECVAYLI: step-up SC doses (0.06 mg/kg and 0.24 mg/kg) and treatment doses: 0.72 mg/kg SC QW.²
    • Lenalidomide: starting Cycle 2+, 25 mg PO once daily (QD) on days 1-21 of each 28-day cycle.²
  • Dose level 2:
    • TECVAYLI: step-up SC doses (0.06 mg/kg and 0.3 mg/kg) and treatment doses: 1.5 mg/kg SC QW.²
    • Lenalidomide: starting Cycle 2+, 15 mg PO QD on days 1-21 of each 28-day cycle.²
• Primary endpoint: safety.²
• Key secondary endpoints: overall response rate (ORR), very good partial response or better (≥VGPR), complete response or better (≥CR), duration of response (DOR), time to response, and TECVAYLI pharmacokinetics.²

Tan et al (2023)² presented the efficacy and safety of TECVAYLI in combination with lenalidomide at a median follow-up of 10.8 months (range, 1.1-16.8).

Results

Treatment Disposition

• At the data cut-off date of March 16, 2023, 31 patients were administered TECVAYLI and lenalidomide.
• Patient and disease characteristics for both dose levels are presented in the table: MajesTEC-2 (Cohort D: TECVAYLI + lenalidomide): Baseline Demographics and Disease Characteristics.

Efficacy

• All patients were evaluable for response. The ORR was 74.2%; ≥CR was 35.5% and ≥VGPR was 64.5%.
• The median follow-up among responders was 11.4 months (range, 3.9-16.8). The median time to first response was 1.2 months (range, 0.8-4.4) and the median time to best response was 3.7 months (range, 1.0-13.1). At data cut-off, the median DOR was not reached.

Safety

• Adverse events (AEs) reported in ≥25% of patients at both dose levels are presented in table: MajesTEC-2 (Cohort D: TECVAYLI + lenalidomide): AEs (≥25% Overall).
• Two patients (6.5%) reported Grade 3/4 febrile neutropenia.
• Treatment discontinuations due to AEs occurred in 5 patients (16.1%).
• Three AE-related deaths (9.7%) were reported (sepsis [n=1], coronavirus disease [COVID-19; n=1], and acute renal failure associated with progressive disease [n=1]).

Cytokine Release Syndrome

• CRS of any grade occurred in 67.7% of patients (n=21). One patient reported a Grade 3 CRS event (with associated Grade 3 hypotension) that occurred during TECVAYLI step-up dose 2.
• The median time to onset of CRS was 2.0 days (range, 1-4). The median duration of CRS was 2.0 days (range, 1-15).
• One patient had a subsequent CRS event during cycle 2. All other CRS events occurred during TECVAYLI step-up dosing or cycle 1.

Neurotoxicity

• Immune effector cell-associated neurotoxicity syndrome (ICANS) events (both Grade 1) were reported in 2 patients (6.5%).

Infections

• Infections of any grade occurred in 80.6% of patients (n=25), with Grade 3/4 infections reported in 45.2% of patients (n=14). The most frequently reported infections were pneumonia (22.6%, all Grade 3/4), COVID-19 (any grade: 19.4%; Grade 3/4: 3.2%), and sepsis (any grade: 16.1%; Grade 3/4: 9.7%).

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 20 June 2024.