SUMMARY

• Janssen does not recommend any practices, procedures or usage that deviate from the approved labeling.
• 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 C is evaluating the efficacy and safety of TECVAYLI in combination with nirogacestat in patients with triple-class exposed relapsed or refractory multiple myeloma (RRMM) who received ≥3 prior lines of therapy (LOTs).^1,2
  • Offner et al (2023)² presented the efficacy and safety of TECVAYLI in combination with nirogacestat in 28 patients at a median follow-up of 14.7 months (range, 0.5-22.9). The overall response rate (ORR) was 74.1% among the 27 response-evaluable patients. The most common adverse events (AEs; any grade) were neutropenia (82.1%), cytokine release syndrome (CRS; 75.0%), and diarrhea (64.3%).

CLINICAL DATA - Majestec-2 study - cohort c

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 C is evaluating the efficacy and safety of TECVAYLI in combination with nirogacestat in 28 patients with triple-class exposed RRMM who received ≥3 prior LOTs.²

Study Design/Methods

• The study design is presented in the Figure: MajesTEC-2 (Cohort C): Study Design.^1,2

Offner et al (2023)² presented the efficacy and safety of TECVAYLI in combination with nirogacestat in 28 patients at a median follow-up of 14.7 months (range, 0.5-22.9). Note that the lower range limit accounts for a patient's death.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• Patient characteristics are summarized in Table: MajesTEC-2 (Cohort C): Baseline Demographics and Disease Characteristics.
• Patients received TECVAYLI for a median duration of 9.4 months (range, 0.03-22.9), and nirogacestat for a median duration of 4.7 months (range, 0.16-15.6).
• At the data cut-off date of March 16, 2023, 12 patients (42.8%) remained on TECVAYLI, and 4 patients (14.3%) remained on nirogacestat.

Efficacy

• The median time to first response was 1.18 months (range, 1.1-2.7) in patients with a confirmed partial response or better (≥PR).
• The ORR was 74.1% (n=20) among the 27 response-evaluable patients. See Table: MajesTEC-2 (Cohort C): Response Summary for additional details.
• Among responders, 87.2% maintained response for ≥12 months. At data cut-off, the median DOR was not reached.

Safety

• Any grade AEs were reported in all patients, with grade 3/4 AEs reported in 92.9% of patients (n=26).
• The incidence of hematologic AEs is outlined in Table: MajesTEC-2 (Cohort C): Hematologic AEs (≥20% Overall). Across all dose levels, febrile neutropenia was reported in 1 patient (3.6%).
• The incidence of nonhematologic AEs is outlined in Table: MajesTEC-2 (Cohort C): Nonhematologic AEs (≥25% Overall).
• Five deaths were reported due to treatment-emergent AEs (sepsis, septic shock, COVID-19, Pneumocystis jirovecii pneumonia, and cardiac arrest).
• Treatment discontinuations related to AEs:
  • TECVAYLI: 2 patients (7.1%); confusional state (n=1), and neutropenia and pneumonia (n=1).
  • Nirogacestat: 17 patients (60.7%); diarrhea (n=3), increased alanine aminotransferase (n=2), increased aspartate aminotransferase (n=2), fatigue (n=2), and cholecystitis, confusional state, COVID-19, general physical health deterioration, hyperamylasemia, malaise, meningitis, mental disorder, muscular weakness, nausea, Pneumocystis jirovecii pneumonia, pneumonia, septic shock, upper gastrointestinal hemorrhage, and vomiting (n=1 each). A patient could have >1 AE leading to discontinuation.
• Dose reductions due to AEs were reported in 3 TECVAYLI patients (10.7%) and 11 nirogacestat patients (39.3%). Dose reductions were patient-specific and not related to the dose levels described in the study design.

Dose-Limiting Toxicities

• Three dose-limiting toxicities (DLTs) were reported in 2 patients.
  • Dose level 1: 3 DLTs were reported in 2 patients: 1 patient with grade 3 gastrointestinal bleeding and grade 3 diarrhea; and 1 patient with grade 3 immune effector cell-associated syndrome (ICANS).
  • Dose level 2 and 3: No DLTs or grade 3 CRS events were reported.

Cytokine Release Syndrome

• The incidence and management of CRS is summarized in Table: MajesTEC-2 (Cohort C): Incidence and Management of CRS.
• Any grade CRS events occurred in 75.0% of patients (n=21). One grade 3 CRS event was reported at dose level 1. Most CRS events occurred during step-up dosing or cycle 1.
• The median time to onset of CRS (relative to the most recent dose) was 2 days (range, 1-3). The median duration of CRS was 2 days (range, 1-33). All CRS events had resolved at the time of data cut-off.

Neurotoxicity

• Two ICANS events occurred; 1 at dose level 1 (grade 3) and 1 at dose level 2 (grade 2).

Infections

• The incidence of infections is presented in Table: MajesTEC-2 (Cohort C): Incidence of Infections (≥20% Overall).
• No DLTs related to infections occurred.
• A total of 78.6% of patients reported either a hypogammaglobulinemia TEAE or ≥1 postbaseline IgG value of <500 mg/dL. Of these, 42.9% of patients were administered intravenous immunoglobulin (IVIG) treatment.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 20 March 2025.