SUMMARY

• Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• In clinical trials, neurotoxic events were defined as adverse events (AEs) under the “nervous system disorder” or “psychiatric disorder” system organ class that were judged by the investigator to be related to study drug, including immune effector cell-associated neurotoxicity syndrome (ICANS) events.^1,2 
• Neurotoxicity, including ICANS has been reported as an AE in the MajesTEC-1, MajesTEC-2, MajesTEC-7, RedirecTT-1, and TRIMM-2 studies.^2-11
• MajesTEC-1 is a phase 1/2, multicohort study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).^2-5,12
  • Cohort A (triple-class exposed) included 165 patients previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody.³
    • Moreau et al (2022)^1,3 published the incidence of neurotoxic events at a median follow-up of 14.1 months. Neurotoxic events assessed by the investigator to be drug related were reported in 14.5% of patients, with 1 grade 4 neurotoxic event reported. Nine ICANS events were reported in 5 patients.
    • Garfall et al (2024)¹² presented the incidence of neurotoxic events at a median follow-up of 30.4 months. No new ICANS events were reported.
  • Cohort C included 40 patients previously treated with a PI, an immunomodulatory agent, an anti-CD38 monoclonal antibody and anti-B-cell maturation antigen (BCMA)-targeted therapies.^2,13
    • Touzeau et al (2024)² published the incidence of neurotoxic events at a median follow-up of 28.0 months. Treatment-emergent neurotoxic events were reported in 27.5% of patients. ICANS events were reported in 4 patients.
  • The prophylactic tocilizumab cohort is evaluating the administration of intravenous (IV) tocilizumab (8 mg/kg) prior to TECVAYLI dosing for the reduction of cytokine release syndrome (CRS) in 24 patients with RRMM.^5,14
    • van de Donk et al (2024)¹⁴ presented the incidence of neurotoxic events at a median follow-up of 8.1 months. Ten events (all grade 1/2) related to neurotoxicity were reported in 5 patients.
• MajesTEC-2 is an ongoing, phase 1b, multicohort study evaluating the safety and efficacy of TECVAYLI in combination with other anticancer therapies in patients with multiple myeloma (MM).^6-8,15
  • Cohort C included 28 patients with RRMM who received TECVAYLI and nirogacestat.⁶
    • Offner et al (2023)⁶ presented the incidence of neurotoxic events at a median follow-up of 14.7 months. Two ICANS events were reported.
  • Cohort D included 31 patients with MM who received TECVAYLI in combination with lenalidomide (Tec-Len).⁷
    • Tan et al (2023)⁷ presented the incidence of neurotoxic events at a median follow-up of 10.8 months. Grade 1 ICANS events were reported in 2 patients.
  • Cohort E included 32 patients with RRMM who received TECVAYLI in combination with DARZALEX FASPRO^® (daratumumab hyaluronidase) and lenalidomide (Tec-DR).⁸
    • Searle et al (2022)⁸ presented the incidence of neurotoxic events at a median follow-up of 8.4 months. No ICANS events were reported.
• MajesTEC-7 is a randomized, phase 3, open-label, multicenter study comparing the safety and efficacy of Tec-DR and TALVEY^® (talquetamab-tgvs) in combination with DARZALEX FASPRO and lenalidomide (Tal-DR) vs DARZALEX FASPRO in combination with lenalidomide and dexamethasone (DRd) in patients with newly diagnosed multiple myeloma (NDMM) who are ineligible or not intended for transplant as initial therapy.^10,16
  • Touzeau et al (2024)¹⁶ presented the incidence of neurotoxic events from the safety run-in (SRI) Cohort 1 at a median follow-up of 13.8 months. One grade 1 ICANS event was reported.
• RedirecTT-1 is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY and TECVAYLI combination in patients with RRMM.^11,17,18
  • Cohen et al (2025)¹¹ published the incidence of neurotoxic events from the phase 1 dose-escalation segment of the RedirecTT-1 study.
    • All dose levels (dose levels 1-5; N=94): At a median follow-up of 20.3 months, ICANS was reported in 3 patients, including 1 grade 3 ICANS event.
• TRIMM-2 is an ongoing, phase 1b, multicohort study evaluating the safety and efficacy of DARZALEX FASPRO regimens in combination with bispecific T-cell redirecting antibodies in patients with RRMM.^9,19
  • Rodriguez-Otero et al (2022)⁹ presented the incidence of neurotoxic events at a median follow-up of 8.6 months in the TECVAYLI and DARZALEX FASPRO cohort. One grade 1 ICANS event was reported.

PRODUCT LABELING

• TECVAYLI (teclistamab-cqyv) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.;  https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.
• TALVEY (talquetamab-tgvs) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-pi.pdf.

clinical data - majestec-1 study

MajesTEC-1 (NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.^2-5,12

Study Design/Methods

The main objectives of MajesTEC-1 are as follows: Part 1 (dose escalation) to determine the recommended phase 2 dose (RP2D) for TECVAYLI; Part 2 (dose expansion) to distinguish safety and tolerability at the RP2D; and Part 3 (the phase 2 component) to evaluate the safety and efficacy of TECVAYLI at the RP2D.^3,20

• Key eligibility criteria:
  • Cohort A: received ≥3 prior lines of therapy (LOTs) including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, no prior BCMA-targeted therapy use.^3,4
  • Cohort C: received ≥3 prior LOTs including a prior PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, enrolled patients who had prior exposure to BCMA-targeted treatment (chimeric antigen receptor [CAR]-T cell and/or antibody drug conjugate [ADC]).²
  • Prophylactic tocilizumab cohort: received ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.⁵
• Safety assessments related to neurotoxicities:
  • Neurotoxicities were identified as AEs under either the ‘nervous system disorder’ or ‘psychiatric disorder’ system organ classes that were judged by the investigator to be related to TECVAYLI, including ICANS events. Grouped terms were used for aphasia, delirium, encephalopathy, and tremor.¹
  • As ICANS events were graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria in phase 2, immune effector cell encephalopathy (ICE) scores were not collected for patients in phase 1. For patients treated at the RP2D in phase 1, all neurotoxicity events and any neurologic AEs that occurred within 28 days after the first dose of TECVAYLI were evaluated for consistency with ICANS.¹

Cohort A Safety Results

Moreau et al (2022)^1,3 published the incidence of neurotoxic events at a median follow-up of 14.1 months (range, 0.3-24.4). Garfall et al (2024)¹² presented the incidence of neurotoxic events at a median follow-up of 30.4 months.

Median Follow-up: 14.1 Months

• Any grade headache was reported in 23.6% of patients (n=39), with grade 3/4 headache reported in 0.6% of patients (n=1).¹
• Details on events judged by the investigator to be related to TECVAYLI are provided in Table: MajesTEC-1 (Cohort A): Characteristics and Management of Investigator-Identified Neurotoxic Events.^1,3
  • A total of 9 ICANS events were reported in 5 patients (3%), all either grade 1 or 2. Of these, 7 ICANS events were reported with concurrent CRS. All 9 ICANS events resolved without discontinuation or dose reduction.³
  • One grade 4 seizure was reported in a patient with bacterial meningitis.One death (progressive multifocal leukoencephalopathy) was reported as an AE related to TECVAYLI.³

Median Follow-up: 30.4 Months

• At a longer median follow-up, no new ICANS events were reported. Additional details on the occurrence of ICANS are provided in the Table: MajesTEC-1 Study (Cohort A): Summary of Treatment-Emergent ICANS.^12,21
• Any grade headache was reported in 24.2% of patients (n=40), with grade 3/4 headache reported in 0.6% of patients (n=1).¹²

Cohort C Safety Results

Touzeau et al (2024)² published the incidence of neurotoxic events in Cohort C of the MajesTEC-1 study at a median follow-up of 28.0 months (range, 0.7-31.1).

• Treatment-emergent neurotoxic events were reported in 27.5% of patients (n=11); 9 patients experienced 1 event, and 2 patients experienced 2 events. See Table: MajesTEC-1 Study (Cohort C): Characteristics and Management of Neurotoxic Events for additional details.²
• ICANS events were reported in 4 patients (10%); all events were concurrent with CRS. ICANS events were grade 1/2 in 3 patients and grade 3 in 1 patient. All ICANS events resolved. Additional details on the occurrence of ICANS are summarized in the Table: MajesTEC-1 Study (Cohort C): Summary of Treatment-Emergent ICANS.^2,22
• Of 13 neurotoxicity events, 8 events (61.5%) were resolved or recovered; 1 event was recovering or resolving at data cutoff, and 4 events did not resolve (2 dysgeusia events, 1 insomnia event and 1 peripheral sensory neuropathy event).²
  • Two events (5.0%; ICANS and peripheral sensory neuropathy) led to TECVAYLI dose interruption, but no patients had dose reductions or treatment discontinuation.²

Prophylactic Tocilizumab Cohort Safety Results

van de Donk et al (2024)¹⁴ presented the incidence of neurotoxic events in the prophylactic tocilizumab cohort of the MajesTEC-1 study at a median follow-up of 8.1 months (range, 0.9-13.2).

• A total of 10 events related to neurotoxicity (defined as a neurological AE considered related by the investigator) were reported in 5 patients. The events included headache, ICANS, myoclonus, dizziness, and insomnia. All events were grade 1/2 and resolved except for grade 2 headache.

cLINICAL DATA - MajestEC-2 STudy

MajesTEC-2 (NCT04722146) is an ongoing, phase 1b, multicohort study evaluating the safety and efficacy of TECVAYLI in combination with other anticancer treatments in patients with MM.^6-8,15

Study Design/Methods

• Key Eligibility Criteria:
  • Cohort C (TECVAYLI and nirogacestat): disease progression within 12 months of last line of therapy; received ≥3 prior LOTs or double refractory to a PI, and an immunomodulatory drug and triple-class exposed to a PI, an immunomodulatory drug and an anti-CD38 monoclonal antibody. Patients with prior exposure to BCMA-targeted therapy were permitted.^6,15
  • Cohort D (Tec-Len): received ≥2 prior LOTs including a PI, an immunomodulatory drug and an anti-CD38 monoclonal antibody, no prior BCMA-targeted therapy.⁷
  • Cohort E (Tec-DR): received 1-3 prior LOTs including a PI, and an immunomodulatory drug, no prior BCMA-targeted therapy.⁸

Cohort C Safety Results

Offner et al (2023)⁶ presented the incidence of neurotoxic events in Cohort C of the MajesTEC-2 study at a median follow-up of 14.7 months (range, 0.5-22.9).

• A total of 2 ICANS events were reported; 1 at dose level 1 (grade 3) and 1 at dose level 2 (grade 2).
• Any grade headache was reported in 25% of patients (n=7), with no reports of grade 3/4 headache.
• Treatment discontinuations related to neurotoxicity:
  • TECVAYLI: confusional state (n=1).
  • Nirogacestat: confusional state, malaise, meningitis, mental disorder, and muscular weakness (n=1 each). A patient could have >1 AE leading to discontinuation.
• A dose-limiting toxicity of grade 3 ICANS was reported in 1 patient at dose level 1.

Cohort D Safety Results

Tan et al (2023)⁷ presented the incidence of neurotoxic events in Cohort D of the MajesTEC-2 study at a median follow-up of 10.8 months (range, 1.1-16.8).

• Grade 1 ICANS events were reported in 2 patients (6.5%).

Cohort E Safety Results

Searle et al (2022)⁸ presented the incidence of neurotoxic events in Cohort E of the MajesTEC-2 study at a median follow-up of 8.4 months (range, 1.1-12.9).

• No ICANS events were reported.
• Any grade insomnia was reported in 37.5% of patients (n=12), with grade 3/4 insomnia reported in 3.1% of patients (n=1).

CLINICAL DATA - MajesTEC-7 study

MajesTEC-7 (NCT05552222) is a randomized, phase 3, open-label, multicenter study comparing the efficacy and safety of Tec-DR and Tal-DR vs DRd in patients with NDMM who are ineligible or not intended for transplant as initial therapy.^10,16

Study Design/Methods

SRI Cohort 1 (Tec-DR)

• A SRI period was used to establish safety prior to enrolling the randomized phase of the study.¹⁶
• Key eligibility criteria: NDMM either ineligible or not intended for autologous stem cell transplant (ASCT).^10,16

Safety Results

Touzeau et al (2024)¹⁶ presented the incidence of neurotoxic events from the SRI of 26 patients in Cohort 1 (Tec-DR) of the MajesTEC-7 study at a median follow-up of 13.8 months (range, 2.0-15.4).

• One grade 1 ICANS event was reported during cycle 1, which resolved.

CLINICAL DATA - Redirectt-1 study - TALVEY + TECVAYLI Cohort

RedirecTT-1 (NCT04586426) is an ongoing, open-label, phase 1b/2 study evaluating the safety and effectiveness of the combination of TALVEY and TECVAYLI in patients with RRMM.^11,17,18

Study Design/Methods

• Key eligibility criteria: relapsed or refractory or intolerant to established therapies including the last LOT, prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.^11,18 

Safety Results

Cohen et al (2025)¹¹ published the incidence of neurotoxic events from the phase 1 dose-escalation segment of the RedirecTT-1 study at a median follow-up of 20.3 months (range, 0.5-37.1) in the all dose levels (dose levels 1-5).

• ICANS was reported in 3 patients (3%), including 1 grade 3 ICANS event; 1 patient had 2 events.
• Two out of 4 ICANS events were concurrent with CRS. All ICANS events occurred during step-up dosing (SUD).
• The median time to onset of ICANS was 2.5 days; the median duration of ICANS was 3 days. All events recovered.

clinical data - Trimm-2 study - tecvayli + Darzalex faspro cohort

TRIMM-2 (NCT04108195) is an ongoing, phase 1b, 2-part, multicohort, open-label study evaluating the safety and efficacy of DARZALEX FASPRO regimens in combination with bispecific T-cell redirection antibodies in patients with RRMM.^9,19

Study Design/Methods

• Key eligibility criteria: received ≥3 prior LOTs including a PI, immunomodulatory drug or were double refractory to PI and immunomodulatory drug; prior anti-CD38 therapy was permitted with a 90-day washout, prior BCMA-targeted therapies were also permitted.^9,19
• Select exclusion criteria: active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM. If either is suspected, brain magnetic resonance imaging (MRI), and lumbar cytology are required.¹⁹

Safety Results

Rodriguez-Otero et al (2022)⁹ presented the incidence of neurotoxic events in the TECVAYLI and DARZALEX FASPRO cohort at a median follow-up of 8.6 months (range, 0.3-19.6).

• Any grade headache was reported in 20% of patients (n=13), with grade 3/4 headache reported in 1.5% of patients (n=1).
• Grade 1 ICANS was reported in 1 patient during SUD and fully resolved in 1 day.

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 02 April 2025.