SUMMARY

• Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• Deaths have been reported in the MajesTEC-1, MajesTEC-2, MajesTEC-4, MajesTEC-7, RedirecTT-1, and TRIMM-2 studies.^1-11 The content herein is limited to these company sponsored clinical trials.
• MajesTEC-1 (MMY1001) is a phase 1/2, multicohort study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).^1-3,10,12-14
  • Cohort A (triple-class exposed) included 165 patients who were previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody.¹
    • Moreau et al (2022)^1,15 published safety and efficacy results of patients receiving TECVAYLI in the MajesTEC-1 study. At a median follow-up of 14.1 months, 68 deaths were reported overall.
    • Nooka et al (2024)¹⁶ published the incidence, timing, and management of infections in patients receiving TECVAYLI in the MajesTEC-1 study. At a median follow-up of 22.8 months, 21 deaths due to infections were reported overall.
    • van de Donk et al (2024)^17,18 conducted a post hoc analysis that evaluated the potential impact of coronavirus disease 2019 (COVID-19) on outcomes in patients receiving the recommended phase 2 dose (RP2D) of TECVAYLI in the MajesTEC-1 study. At a median follow-up of 22.8 months, 18 deaths due to COVID-19 infections were reported; 4deaths from COVID-19 were considered by the investigators to be related to TECVAYLI treatment.
    • Costa et al (2024)¹⁴ presented a subgroup analysis evaluating the safety and efficacy outcomes in patients with high-risk (HR) features from the MajesTEC-1 study. At a data cutoff of Aug 22, 2023, a total of 94 deaths were reported in the overall RP2D population. Details on deaths in patients with HR features are provided in Table: MajesTEC-1 (Cohort A): Mortality in Patients With HR Features.
  • 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.^10,19
    • Touzeau et al (2024)¹⁰ published the safety and efficacy of TECVAYLI in Cohort C of the MajesTEC-1 study. At a median follow-up of 28.0 months, 25 deaths were reported.
  • 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.^3,20
    • van de Donk et al (2024)²⁰ presented the effects of prophylactic tocilizumab for the reduction of CRS in patients treated with TECVAYLI. At a median follow-up of 8.1 months, 1 death was reported due to an adverse event (AE; pulmonary embolism).
• MajesTEC-2 (MMY1004) 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).^4-6,21,22
  • Cohort A included 17 patients with RRMM who received TECVAYLI in combination with DARZALEX FASPRO^® (daratumumab and hyaluronidase) and pomalidomide.²²
    • D’Souza et al (2024)²² presented safety and efficacy in Cohort A. At a median follow-up of 16.2 months, 1 death due to pseudomonal bacteremia and 3 deaths due to COVID-19-related pneumonia were reported.
  • Cohort C included 28 patients with RRMM who received TECVAYLI and nirogacestat.⁴
    • Offner et al (2023)⁴ presented safety and efficacy in Cohort C. At a median follow-up of 14.7 months (range, 0.5-22.9), 5 deaths were reported due to treatment-emergent adverse events (TEAEs).
  • Cohort D included 31 patients with multiple myeloma (MM) who received TECVAYLI in combination with lenalidomide (Tec-Len).⁵
    • Tan et al (2023)⁵ presented safety and efficacy in Cohort D. At a median follow-up of 10.8 months, 3 deaths were reported due to AEs.
  • Cohort E included 32 patients with RRMM who received TECVAYLI in combination with DARZALEX FASPRO and lenalidomide (Tec-DR).⁶
    • Searle et al (2022)⁶ presented safety and efficacy in Cohort E. At a median follow-up of 8.4 months, 2 deaths were reported due to AEs.
• MajesTEC-4 (EMN30; MMY3003) is an open-label, randomized, multicenter, phase 3 study assessing the efficacy and safety of Tec-Len and TECVAYLI alone vs lenalidomide alone as maintenance therapy after an autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (NDMM).^23,24 
  • Zamagni et al (2024)²⁴ presented the preliminary efficacy and safety results from the safety run-in (SRI) of Cohort 1 (Tec-Len; TECVAYLI weekly [QW] to every 4 weeks [Q4W]) at a median follow-up of 21.1 months, Cohort 2 (Tec-Len; TECVAYLI Q4W) at a median follow-up of 9.2 months, and Cohort 3 (TECVAYLI [Q4W]) at a median follow-up of 9.2 months.
    • At a median follow-up of 9.2 months, 1 death due to a COVID-19-related TEAE was reported in SRI Cohort 2. No deaths were reported in SRI Cohorts 1 and 3.
• MajesTEC-7 (MMY3005) 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 NDMM who are ineligible or not intended for transplant as initial therapy.^9,25
  • Touzeau et al (2024)²⁵ presented the initial results from the SRI Cohort 1 (Tec-DR). At a median follow-up of 13.8 months, 1 patient died from influenza pneumonia in cycle 3.
• RedirecTT-1 (MMY1003) is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY and TECVAYLI in patients with RRMM.^7,11,26,27
  • Cohen et al (2025)^11,28 published safety and efficacy results 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, 14 deaths were reported due to AEs, of which 11 deaths were due to infections.
• TRIMM-2 (MMY1002) 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.^8,22,29
  • D’Souza et al (2024)²² presented safety and efficacy results from the TECVAYLI + DARZALEX FASPRO + pomalidomide cohort in 10 patients. At a median follow-up of 38.3 months, deaths due to infection were reported in 2 patients.
  • Rodriguez-Otero et al (2022)⁸ presented safety and efficacy results from the TECVAYLI and DARZALEX FASPRO cohorts in 65 patients. At a median follow-up of 8.6 months, 4 deaths were reported due to AEs.

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 (MMY1001; clinicaltrials.gov identifiers: NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.^1-3,10,12-14

Study Design/Methods

The main objectives are as follows: Part 1 (dose escalation) to determine the 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 efficacy of TECVAYLI at the RP2D.^1,30

• Key eligibility criteria:
  • Cohort A: ≥3 prior lines of therapy (LOTs) including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, no prior BCMA-targeted therapy use.^1,2
  • Cohort C: ≥3 prior LOTs, 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]).¹⁰
  • Prophylactic tocilizumab cohort: ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.³
• Primary endpoint for Cohort A and Cohort C: overall response rate (ORR).^1,2,10
• Key secondary endpoint for Cohort A and Cohort C: safety.^1,2,10
• Endpoint for prophylactic tocilizumab cohort: incidence of CRS.³

Cohort A Safety Results

Moreau et al (2022)^1,15 published safety and efficacy results of patients receiving TECVAYLI in the MajesTEC-1 study at a median follow-up of 14.1 months (range, 0.3-24.4).

• A total of 68 deaths (41.2%) were reported: 41 deaths (24.8%) were due to progressive disease, 14 deaths (8.5%) were due to AEs unrelated to TECVAYLI, 5 deaths (3.0%) were due to AEs considered by the investigator to be related to TECVAYLI, and 8 deaths (4.8%) were due to other causes, summarized in the Table: MajesTEC-1 Study (Cohort A): Mortality.

Nooka et al (2024)¹⁶ published the incidence, timing, and management of infections in patients receiving TECVAYLI in the MajesTEC-1 study at a median follow-up of 22.8 months (range, 0.3-33.6).

• A total of 21 deaths (12.7%) were reported due to infections: COVID-19 (n=18), bilateral pneumonia (unknown pathogen; n=1), pneumococcal pneumonia (n=1), and progressive multifocal leukoencephalopathy (PML; n=1).
  • One patient (0.6%) who died from PML after 16.1 months had discontinued TECVAYLI treatment 2.5 months earlier due to grade 4 PML.
• Most patients were enrolled before COVID-19 vaccines were available. Once the COVID-19 vaccine was available, 60% of patients (n=99) received at least one dose, including 13/18 patients who died from COVID-19 (12 received all doses after starting TECVAYLI; one received 2 doses prior then a third dose during TECVAYLI treatment).
  • Patients who were unvaccinated tended to die earlier (0.7–5.9 months; between January 2021 and November 2021 [n=6]) than vaccinated patients (4.3-25.9 months; between April 2021 and December 2022 [n=12]).
  • At the time of death, 13/18 patients had partial response or better (≥PR) and 2/18 had stable disease (3 deaths were reported before any post-baseline efficacy assessments).
• Deaths due to respiratory infections were reported in 2 patients (1.2%); 1 after 1.9 months (bilateral pneumonia, pathogen unknown) and 1 after 10.6 months (pneumococcal pneumonia).

van de Donk et al (2024)^17,18 conducted a post hoc analysis that evaluated the potential impact of COVID-19 on outcomes in patients receiving the RP2D of TECVAYLI in the MajesTEC-1 study (data cutoff date January 4, 2023). Of note, MajesTEC-1 recruitment occurred concurrently with the pandemic, starting in March of 2020. COVID-19 vaccines were not approved until late 2020 to early 2021, approximately 9 months into MajesTEC-1 enrollment.

Methods

• Infections were managed per institutional guidelines and/or TECVAYLI interruption; vaccination (including booster doses) was recommended per availability.
• Patients with grade 5 COVID-19 infection were censored at the time of last disease evaluation for analyses of progression-free survival (PFS) (n=17) and duration of response (DOR) (n=13) if death occurred without disease progression. All patients who died from COVID-19 (n=18) were censored at the time of death for analysis of overall survival (OS).

Safety Results

• Any-grade and grade 3/4 COVID-19 infection was reported in 29.1% (n=48) and 21.2% (n=35) of patients, respectively, and deaths due to COVID-19 infection were reported in 10.9% (n=18) of patients; 4 deaths from COVID-19 were considered by the investigators to be related to TECVAYLI treatment.
• A total of 7.9% of patients (n=13), including 1/18 patients who died of COVID-19, were vaccinated at least once with a COVID-19 vaccine before TECVAYLI was administered. The patient who died received 2 doses before starting TECVAYLI.
• A total of 60% of patients (n=99), including 13/18 patients who died of COVID19, were vaccinated at least once with a COVID-19 vaccine on study overall (1 dose, n=3; 2 doses, n=4; 3 doses, n=3; 4 doses, n=3 [the patient who was vaccinated pre-TECVAYLI received their 3^rd dose on-study]).
• Patients who never received a COVID-19 vaccination tended to die of COVID-19 earlier during TECVAYLI treatment (range, 0.7-5.9 months) compared to patients who received ≥1 COVID-19 vaccination (range, 2.4-25.9 months). A greater proportion of deaths were reported in 2021 (5/5 vs 5/13 respectively) compared to 2022 (0/5 vs 8/13, respectively).

Costa et al (2024)¹⁴ presented a subgroup analysis evaluating the safety and efficacy outcomes in patients with HR features from the MajesTEC-1 study.

• At a data cutoff of Aug 22, 2023, a total of 94 deaths (57%) were reported in the overall RP2D population. Details on deaths in patients with HR features are provided in Table: MajesTEC-1 (Cohort A): Mortality in Patients With HR Features.

Cohort C Safety Results

Touzeau et al (2024)¹⁰ published the safety and efficacy of TECVAYLI in Cohort C of the MajesTEC-1 study at a median follow-up of 28.0 months (range, 0.7-31.1).

• A total of 25 deaths (62.5%) were reported. Disease progression was the primary cause of death in 12 patients (30.0%). Two patients (5.0%) died due to events that investigators considered were related to TECVAYLI treatment (COVID-19, n=1; cardiac arrest, n=1). Of the 10 patients with grade 5 TEAEs:
  • A total of 8 patients (20.0%) died due to AEs (COVID-19 [n=4; 10%], and 1 patient each [2.5%] due to cardiac arrest, cardiac failure, coronary artery dissection, and sudden death).
  • The other 2 grade 5 AEs were due to disease progression. The patient who suffered cardiac arrest had pneumonia that began 10 days prior to death.

Prophylactic Tocilizumab Cohort Safety Results

van de Donk et al (2024)²⁰ presented the effects of prophylactic tocilizumab for the reduction of CRS in patients treated with TECVAYLI in the prophylactic tocilizumab cohort of the MajesTEC-1 study at a median follow-up of 8.1 months (range, 0.9-13.2).

• One death was reported due to an AE (pulmonary embolism), which was reported 20 days after the last TECVAYLI dose (previously reported at a 2.6-month follow-up).

clinical data - Majestec-2 Study

MajesTEC-2 (MMY1004; clinicaltrials.gov identifier: NCT04722146) is an ongoing, phase 1b, multicohort, open-label study evaluating the safety and efficacy of TECVAYLI in combination with other anticancer treatments in patients with MM.^4-6,22,31

Study Design/Methods

Key Eligibility Criteria

• Cohort A (TECVAYLI and DARZALEX FASPRO and pomalidomide): received 1 to 3 prior LOTs, including a PI and lenalidomide.²²
• Cohort C (TECVAYLI and nirogacestat): disease progression within 12 months of last LOT; ≥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.^4,21
• 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.⁵
• Cohort E (Tec-DR): received 1-3 prior LOTs including a PI, and an immunomodulatory drug, no prior BCMA-targeted therapy.⁶

Primary Endpoints

• Cohort A: safety and dose-limiting toxicities.²²
• Cohort C: safety, tolerability, and optimal doses.⁴
• Cohort D: safety.⁵
• Cohort E: safety, dose-limiting toxicities, and laboratory abnormalities.⁶

Cohort A Safety Results

D’Souza et al (2024)²² presented safety and efficacy in Cohort A of the MajesTEC-2 study at a median follow-up of 16.2 months (range, 0.5-34.5).

• One death due to pseudomonal bacteremia and 3 deaths due to COVID-19-related pneumonia were reported.

Cohort C Safety Results

Offner et al (2023)⁴ presented safety and efficacy in Cohort C of the MajesTEC-2 study at a median follow-up of 14.7 months (range, 0.5-22.9).

• Five deaths due to TEAEs were reported: sepsis, septic shock, COVID-19, cardiac arrest, and Pneumocystis jirovecii pneumonia.

Cohort D Safety Results

Tan et al (2023)⁵ presented safety and efficacy in Cohort D of the MajesTEC-2 study at a median follow-up of 10.8 months (range, 1.1-16.8).

• Three AE-related deaths (9.7%) were reported (sepsis [n=1], COVID-19 [n=1], and acute renal failure associated with progressive disease [n=1]).

Cohort E Safety Results

Searle et al (2022)⁶ presented safety and efficacy in Cohort E of the MajesTEC-2 study at a median follow-up of 8.4 months (range, 1.1-12.9).

• Two deaths were reported due to AEs: COVID-19 (n=1, 77 days after last dose) and multi-organ failure related to sepsis (n=1).

CLINICAL DATA - MajesTEC-4 study

MajesTEC-4 (EMN30; MMY3003; clinicaltrials.gov identifier NCT05243797) is an open-label, randomized, multicenter, phase 3 study evaluating the safety and efficacy of Tec-Len and TECVAYLI alone vs lenalidomide alone as maintenance therapy in patients with NDMM.^23,24

Study Design/Methods

SRI Cohorts

• A SRI period consisting of 3 cohorts was used to establish safety prior to enrolling the randomized phase of the study.²⁴
• Maintenance regimen (2-year fixed duration): patients who achieved a CR on Tec-Len after 1 year discontinued TECVAYLI and continued on lenalidomide for an additional year.²⁴
• Key eligibility criteria: NDMM, received 4-6 cycles of 3- or 4-drug induction therapy (PI ± immunomodulatory drug ± anti-CD38 antibody), and ASCT (single or tandem ASCT permitted) and/or consolidation with ≥PR.²⁴
• Primary endpoints: PFS and 12-month minimal residual disease (MRD)-negative CR.²⁴
• Key secondary endpoint: safety.²⁴

Safety Results

Zamagni et al (2024)²⁴ presented the preliminary efficacy and safety results from SRI Cohort 1 (Tec-Len; TECVAYLI QW to Q4W) at a median follow-up of 21.1 months (range, 14.8-23.8), SRI Cohort 2 (Tec-Len; TECVAYLI Q4W) at a median follow-up of 9.2 months (range, 1.2-12.2), and SRI Cohort 3 (TECVAYLI Q4W) at a median follow-up of 9.2 months (range, 3.7-11.5).

• One death due to a COVID-19-related TEAE was reported in SRI Cohort 2.
• No deaths were reported in SRI Cohorts 1 and 3.

CLINICAL DATA - MAJESTEC-7 STUDY - TECVAYLI + TALVEY COHORT

MajesTEC-7 (MMY3005; clinicaltrials.gov identifier NCT05552222) is a randomized, phase 3, open-label, multicenter study comparing the safety and efficacy of Tec-DR and Tal-DR vs DRd in patients with NDMM who are ineligible or not intended for transplant as initial therapy.^9,25

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.²⁵
• Key eligibility criteria: NDMM either ineligible or not intended for ASCT.^9,25
• Primary endpoints: PFS, 12-month MRD-negative CR.^9,25
• Key secondary endpoint: safety.^9,25

Safety Results

Touzeau et al (2024)²⁵ presented the initial results 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 patient died from influenza pneumonia in cycle 3.

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

RedirecTT-1 (MMY1003; clinicaltrials.gov identifier: 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.^7,11,26,27

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.^11,27
• Primary endpoints: dose limiting toxicity and ORR.^11,27

Safety Results

Cohen et al (2025)^11,28 published the safety and efficacy results from the phase 1 dose-escalation segment of the RedirecTT-1 study.

• All dose levels (N=94): At a median follow-up of 20.3 months (range, 0.5-37.1), deaths due to AEs were reported in 14 patients (15%), of which 11 patients (12%) died due to infections. See Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): AEs Leading to Death in Patients Across Dose Levels 1-5 for additional details.^11,28
• RP2R (n=44): At a median follow-up of 18.2 months (range, 0.7-27.0), deaths due to AEs were reported 5 patients (11.4%); deaths due to infections were reported in 3 patients (6.8%).²⁷ 
• The investigator attributed 6 deaths due to a study drug, but there is insufficient evidence to confirm whether the other events were related to treatment.¹¹ 
• A total of 4 patients (4%) died due to disease progression.¹¹

clinical data - TRIMM-2 STUDY

TRIMM-2 (MMY1002; clinicaltrials.gov identifier: 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.^8,22,29

Study Design/Methods

• Key eligibility criteria: received ≥3 prior LOTs (including a PI and an immunomodulatory drug) or double refractory to a PI and an immunomodulatory drug; anti-CD38 monoclonal antibody >90 days prior, and prior bispecific antibodies (BsAb) and CAR-T therapy were allowed.²⁹
• Key primary endpoint: safety.²⁹

Safety Results

D'Souza et al (2024)²² presented the safety and efficacy results from the TECVAYLI + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 38.3 months (range, 1.2-39.6).

• Deaths due to infection were reported in 2 patients; 1 due to pneumonia and 1 due to COVID-19 pneumonia.

Rodriguez-Otero et al (2022)⁸ presented safety and efficacy results from the TECVAYLI and DARZALEX FASPRO cohorts in the TRIMM-2 study at a median follow-up of 8.6 months (range, 0.3-19.6).

• Four deaths were reported due to AEs (bacterial pneumonia, sepsis, hepatic failure and COVID-19). The deaths were considered unrelated to treatment with TECVAYLI or DARZALEX FASPRO.

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 11 February 2025.