SUMMARY

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• Infections have been reported as an adverse event (AE) in the MajesTEC-1, MajesTEC-2, MajesTEC-4, MajesTEC-5, MajesTEC-7, RedirecTT-1, and TRIMM-2 studies.^1-16
• 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).^1-3,17-20
  • Cohort A (triple-class exposed) included 165 patients with RRMM who were previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody.¹
    • van de Donk et al (2024)^21,22 conducted a post hoc analysis that evaluated the potential impact of the 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, 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.
    • Nooka et al (2023)²³ 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), any grade infections were reported in 80% of patients, with grade 3/4 infections reported in 55.2% of patients.
    • Garfall et al (2024)²⁰ presented the incidence of infections at a longer median follow-up of 30.4 months. Any grade infections were reported in 78.8% of patients, with grade 3/4 infections reported in 55.2% of patients. No new deaths due to COVID-19 treatment-emergent adverse events (TEAEs) were reported since the 22.8-month follow-up.
  • Cohort C included 40 patients with RRMM, previously treated with a PI, an immunomodulatory agent, an anti-CD38 monoclonal antibody and anti-B-cell maturation antigen (BCMA)-targeted therapies.^10,17 Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
    • Touzeau et al (2024)¹⁰ published the incidence of infections at a median follow-up of 28.0 months (range, 0.7-31.1). Any grade infections were reported in 70% of patients overall (n=28). Of these, 32.5% (n=13) were grade 3/4, and 10% (n=4) were grade 5.
  • 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.^3,24 Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
    • van de Donk et al (2024)²⁴ presented the incidence of infections at a median follow-up of 8.1 months (range, 0.9-13.2). Any grade infections were reported in 79.2% of patients, with grade 3/4 infections reported in 25.0% of patients.
  • Miao et al (2023)²⁵ presented the population pharmacokinetic (PK) analysis and exposure/safety relationships of TECVAYLI in patients with RRMM in the MajesTEC-1 study for the occurrence of select grade ≥3 TEAEs, including infections.
• 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).^4-6,11,26 Janssen does not recommend the use of TECVAYLI or DARZALEX FASPRO^® (daratumumab and hyaluronidase) in a manner that is inconsistent with the approved labeling.
  • Cohort A included 17 patients with RRMM who received TECVAYLI in combination with DARZALEX FASPRO and pomalidomide.¹¹
    • D’Souza et al (2024)¹¹ presented the incidence of infections at a median follow-up of 16.2 months (range, 0.5-34.5). Any-grade infections were reported in 94.1% of patients overall (n=16) and grade 3/4 infections were reported in 64.7% of patients (n=11).
  • Cohort C included 28 patients with RRMM who received TECVAYLI and nirogacestat.⁴
    • Offner et al (2023)⁴ presented the incidence of infections at a median follow-up of 14.7 months (range, 0.5-22.9). The most common infections (≥20%) were COVID-19, pneumonia, bronchitis, and upper respiratory tract infections. The most frequently reported grade 3/4 infection was pneumonia.
  • Cohort D included 31 patients with MM who received TECVAYLI in combination with lenalidomide (Tec-Len).⁵
    • Tan et al (2023)⁵ presented the incidence of infections at a median follow-up of 10.8 months (range, 1.1-16.8). Any grade infections were reported in 80.6% of patients, with grade 3/4 infections reported in 45.2% of patients.
  • 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 the incidence of infections at a median follow-up of 8.4 months (range, 1.1-12.9). Any grade infections (≥1) were reported in 90.6% of patients, and ≥1 grade 3/4 infections were reported in 37.5% of patients.
• MajesTEC-4 (EMN30; MMY3003) is an open-label, randomized, multicenter, phase 3 study assessing the safety and efficacy 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).^15,27 Janssen does not recommend the use of TECVAYLI or lenalidomide in a manner that is inconsistent with the approved labeling.
  • Zamagni et al (2024)²⁷ presented the incidence of infections from a safety run-in (SRI) consisting of 3 cohorts.
    • Cohort 1 (Tec-Len; TECVAYLI weekly [QW] to once every 4 weeks [Q4W]; N=32): At a median follow-up of 21.1 months (range, 14.8-23.8), any-grade infections were reported in 93.8% of patients (n=30) and grade 3/4 infections were reported in 37.5% of patients (n=12).
    • Cohort 2 (Tec-Len; TECVAYLI Q4W; N=32): At a median follow-up of 9.2 months (range, 1.2-12.2), any-grade infections were reported in 78.1% of patients (n=25) and grade 3/4 infections were reported in 28.1% of patients (n=9).
    • Cohort 3 (TECVAYLI Q4W; N=30): At a median follow-up of 9.2 months (range, 3.7-11.5), any-grade infections were reported in 76.7% of patients (n=23) and grade 3/4 infections were reported in 20.0% of patients (n=6).
• MajesTEC-5 (GMMG-HD10; DSMM-XX; MMY2003) is an open-label, nonrandomized, phase 2 study assessing the safety and efficacy of TECVAYLI- and TALVEY^® (talquetamab-tgvs)-based combination regimens in patients with transplant-eligible newly diagnosed multiple myeloma (TE-NDMM).^12,13 Janssen does not recommend the use of TECVAYLI or TALVEY in a manner that is inconsistent with the approved labeling.
  • Raab et al (2024)¹³ presented the incidence of infections from 3 induction cohorts of the MajesTEC-5 study.
    • Arm A (Tec [QW]-DR; n=10): Any-grade infections were reported in 100% of patients (n=10), and grade 3/4 infections were reported in 40% of patients (n=4).
    • Arm A1 (Tec [Q4W]-DR; n=20): Any-grade infections were reported in 90% of patients (n=18), and grade 3/4 infections were reported in 45% of patients (n=9).
    • Arm B (TECVAYLI Q4W in combination with DARZALEX FASPRO, bortezomib, and lenalidomide; Tec [Q4W]-DVR; n=19): Any-grade infections were reported in 57.9% of patients (n=11), and grade 3/4 infections were reported in 21.1% of patients (n=4).
• MajesTEC-7 (MMY3005) is a randomized, phase 3, open-label, multicenter study comparing the safety and efficacy of Tec-DR and TALVEY 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.^9,28 Janssen does not recommend the use of TECVAYLI, TALVEY, or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
  • Touzeau et al (2024)²⁸ presented the incidence of infections from SRI Cohort 1 (Tec-DR) at a median follow-up of 13.8 months. Any-grade infections were reported in 100% of patients, with grade 3/4 infections reported in 30.8% of patients.
• RedirecTT-1 (MMY1003) is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY AND TECVAYLI combination in patients with RRMM.^7,14,16,29 Janssen does not recommend the use of TALVEY AND TECVAYLI in a manner that is inconsistent with the approved labeling.
  • Cohen et al (2025)^16,30 published the incidence of infections 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 (range, 0.5-37.1), any-grade infections were reported in 89% of patients, and grade 3/4 infections were reported in 64% of patients.
• 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.^8,11,31 Janssen does not recommend the use of TECVAYLI or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
  • D’Souza et al (2024)¹¹ presented the incidence of infections in the TECVAYLI + DARZALEX FASPRO + pomalidomide cohort (N=10) at a median follow-up of 38.3 months (range, 1.2-39.6). Any-grade infections were reported in 90% of patients (n=9), and grade 3/4 infections were reported in 60% of patients (n=6).
  • Rodriguez-Otero et al (2022)⁸ presented the incidence of infections in the TECVAYLI and DARZALEX FASPRO cohorts at a median follow-up of 8.6 months (range, 0.3-19.6). Any-grade infections were reported in 67.7% of patients, and grade 3/4 infections were reported in 27.7% of patients.
• Other relevant data has been identified in addition to the data summarized above:
  • Siegel et al (2024)³² described a case of a female patient with MM treated sequentially with TECVAYLI and TALVEY who developed renal failure from BK virus (BKV) nephritis and fatal neurologic decline from progressive multifocal leukoencephalopathy (PML).

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.^1-3,10,18-20

Study Design/Methods

The main objectives 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 of TECVAYLI at the RP2D; Part 3 (the phase 2 component) to evaluate the efficacy of TECVAYLI at the RP2D.^1,33

• 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

van de Donk et al (2024)^21,22 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 were reported 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).

Results

Safety

• 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.
• TECVAYLI administration was interrupted in 17.6% (n=29) of patients.
• 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 COVID-19, 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).
• Supportive therapies were used to treat COVID-19 in 24.2% of patients, including antivirals (remdesivir) in 9.1% of patients. Additional details on management of COVID-19 infections are summarized in Table: Management of COVID-19 Infections in the MajesTEC-1 Study.

Nooka et al (2023)²³ 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).

Methods

• This exploratory analysis of infections occurring in patients from MajesTEC-1 (data cutoff date January 4, 2023) included overall infections and selected categories of clinically relevant infections often observed in MM patients (including viral, COVID-19, fungal, Pneumocystis jirovecii pneumonia [PJP], respiratory and gastrointestinal [GI] infections).
• Monitoring for infections occurred frequently; infections were graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03.
• TECVAYLI was delayed during febrile neutropenia, grade 3 neutropenia with infection, grade 4 neutropenia, or grade ≥3 nonhematologic toxicities requiring intervention or associated with an AE, and interrupted in patients with hepatitis B virus (HBV) reactivation until infection was controlled.

Results

Safety

• See Table: MajesTEC-1 Study (Cohort A): Incidence and Maximum Toxicity Grade of Infections for a summary of the incidence and types of infections.
• Any-grade infections were reported in 80% of patients (n=132), with grade 3/4 infections reported in 55.2% of patients (n=91).
  • The median time to first onset of any grade infection was 1.7 months (range, 0.0-24.7) and grade ≥3 infection was 4.2 months (range, 0.0-34.6).
  • Grade 3/4 infections were more frequent within 2 months of starting TECVAYLI relative to other time points in the study.
  • Fewer grade ≥3 infections were reported between 1 and 1.5 years in patients who switched to biweekly dosing by 1 year as compared to those who remained on QW dosing at 1 year (15.6% vs 33.3%).
• Opportunistic infections were reported in 9.1% of patients (n=15).
• Treatment discontinuation related to infection was reported in 3% of patients (n=5); due to grade 3 adenoviral pneumonia and concurrent grade 3 PJP (n=1), grade 3 COVID-19 (n=1), grade 4 COVID-19 (n=1), grade 4 PML; n=1, from which the patient died) and grade 4 sepsis (n=1) respectively.
• A total of 21 deaths (12.7%) related to infections were reported.

Key Viral Infections (excluding COVID-19)

• Infections caused by an identified viral pathogen were reported in 12.1% of patients (n=20).
• Viral infections were most commonly caused by adenovirus (n=5; after 3-27 months), parvovirus B19 (n=5; after 11-18 months), oral herpes (n=4; after 0.6-3 months, including 3 confirmed herpes simplex virus [HSV] infections), and herpes zoster (n=3; after 5-24 months).
• Approximately half of the viral infections were reported within 6.6 months of starting TECVAYLI.
• Viral reactivations were reported as follows:
  • Adenoviral (grade 2) reactivation in 1 patient after 2.4 months.
  • Cytomegalovirus (CMV; grade 3) reactivation in 1 patient after 4.2 months.
  • CMV viremia in 2 patients after 1.2 months and 10.7 months, respectively.
  • HBV (grade 3) reactivation in 1 patient after 3.5 months (without prophylaxis).
• Treatment discontinuations were reported in 2 patients, one at 2.5 months (concurrent grade 3 adenoviral pneumonia and PJP) and the other at 13.6 months (grade 4 PML). The patient with grade 4 PML did not restart TECVAYLI treatment and died after 16.1 months.

COVID-19 Infections

• COVID-19 positivity was reported in 29.1% of patients (n=48) overall, with grade 3/4 events reported in 21.1% of patients (n=25).
• COVID-19 infections (all grades) were observed throughout TECVAYLI treatment.
• 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]).
• Death due to COVID-19 infections was reported in 18 patients. At the time of death, 13/18 patients had a partial response (PR) or better and 2/18 patients had stable disease (3 deaths were reported before any post baseline efficacy assessments).
• Discontinuations due to COVID-19 infections were reported in 2 patients (one due to a grade 3 COVID-19 infection at 20.7 months and another due to a grade 4 infection at 16.4 months).

Fungal Infections (excluding PJP)

• Fungal infections were reported in 5.5% of patients (n=9).
• Most fungal infections were reported approximately within the first 3 months of TECVAYLI treatment.
• A total of 4 patients had Candida infections of which 3 patients had grade 2 oral candidiasis and 1 patient had grade 2 skin candida. These were observed after approximately 1 month of starting TECVAYLI treatment, with the exception of 1 case of oral candidiasis after 14.8 months. No fungemia was reported.
• A single grade 2 Aspergillus infection was observed in 1 patient, however the patient died from COVID-19 infection before the Aspergillus infection was resolved.

PJP Infections

• PJP infections (all grade 3/4) were reported in 7 patients (4.2%), occurring after 2.5-7.8 months of TECVAYLI treatment and lasting for 8-60 days.
• Four patients were not receiving prophylaxis at the time of infection; 2 of these 4 patients had stopped prophylaxis 3-4 months prior to the infection and 2 patients never received PJP prophylaxis.
• Treatment discontinuation was reported in 1 patient with concurrent grade 3 PJP and grade 3 adenoviral pneumonia.
• PJP resolved in all patients.

Respiratory Infections (excluding PJP and COVID-19)

• Respiratory infections were reported in 57.6% of patients (n=95), with grade 3/4 respiratory infections reported in 19.4% of patients.
• Respiratory infections (all grades) were observed throughout TECVAYLI treatment. Pneumonia was most frequently observed, most commonly due to pseudomonal pneumonia (where causative pathogen was identified).
• Deaths due to respiratory infections were reported after 1.9 months (bilateral pneumonia, pathogen unknown) and after 10.6 months (pneumococcal pneumonia).
• No treatment discontinuations were observed, however there were 30 treatment interruptions due to grade 3 infections.

GI Infections

• GI infections were reported in 9.1% of patients (n=15).
• GI infections mostly were reported within the first 13 months of TECVAYLI treatment.
• Treatment was interrupted in 2 patients with grade 3 infections, 1 patient with diverticulitis (after 2.6 months and after patient had discontinued TECVAYLI due to concurrent grade 3 PJP and grade 3 adenoviral pneumonia) and 1 patient with infectious enterocolitis (after 9.6 months).

Garfall et al (2024)²⁰ presented the incidence of infections in Cohort A of the MajesTEC-1 study at a longer median follow-up of 30.4 months.

Results

Safety

• The incidence of treatment-emergent infections at a median follow-up of 30.4 months are summarized in Table: MajesTEC-1 (Cohort A): Treatment-Emergent Infections.
• A total of 22 deaths due to infection were reported, of which 18 deaths were due to COVID-19.
  • No new deaths due to COVID-19 TEAEs have been reported since the 22.8-month follow-up.
• Treatment discontinuations due to infections were reported in 5 patients.

Cohort C

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

Results

Safety

• At a median follow-up of 28.0 months (range, 0.7-31.1), infections were reported in 70.0% of patients overall (n=28). Of these, 32.5% (n=13) were grade 3/4, and 10% (n=4) were grade 5. Details are provided in Table: MajesTEC-1 Study (Cohort C): Incidence of Infections ≥10%.
• Of the 3 patients (7.5%) who discontinued TECVAYLI due to AEs, 1 case was considered treatment-related by the investigator (hepatitis E virus infection).
• One patient died due to COVID-19 that investigators considered related to TECVAYLI treatment.
• Of the 10 patients with grade 5 TEAEs:
  • One patient had a cause of death reported as cardiac arrest. This patient had pneumonia that began 10 days prior to death.
  • Four patients (10%) had a cause of death reported as COVID-19. Three patients had received at least 1 COVID-19 vaccination prior to TECVAYLI treatment, and 1 patient had no record of prior COVID-19 vaccination. Patient recruitment in Cohort C began in October 2020, coinciding with the COVID-19 pandemic and overlapping with peak infection and death rates globally per the World Health Organization data.

Prophylactic Tocilizumab Cohort

van de Donk et al (2024)²⁴ presented the incidence of infections in the prophylactic tocilizumab cohort of the MajesTEC-1 study at a median follow-up of 8.1 months (range, 0.9-13.2).

Results

Safety

• In the prophylactic tocilizumab cohort (N=24), 79.2% of patients (n=19) experienced any grade infections and 25% of patients (n=6) experienced grade 3/4 infections.
  • Infections reported in the prophylactic tocilizumab cohort were pneumonia (n=4), bacterial infection (n=1), diverticulitis (n=1), CMV infection (n=1), sepsis (n=1), and septic shock (n=1).

Population PK and Exposure-Relationships in MajesTEC-1

Miao et al (2023)²⁵ developed a population PK model to evaluate the exposure of TECVAYLI in baseline demographic subgroups and other covariates. In addition, the exposure-safety relationships were explored using available data from 338 patients in the phase 1/2 MajesTEC-1 study.

Methods

• Select safety analysis: The occurrence of grade ≥3 TEAEs, including infections, were estimated in patients who received TECVAYLI subcutaneous (SC) dosing in the phase 1/2 (Cohort A) portion of the trial (n=217). The analysis used predicted maximum concentration following the first treatment dose (C_max,1stdose) and predicted maximum concentration following the first four QW treatment doses (C_max,4doses) to characterize the exposure-safety relationship.

Results

Population PK Analysis

• Among 338 patients (4840 PK observations) from the phase 1/2 MajesTEC-1 study, 83 patients (1976 PK observations) were administered TECVAYLI IV, and 255 patients (2864 PK observations) were administered TECVAYLI SC.
• Among patients who received TECVAYLI SC, 28 patients (604 PK observations) received doses <RP2D, 203 (1679 PK observations) received RP2D, 21 patients (502 PK observations) received doses >RP2D, and 3 patients (79 PK observations) received flat dosing.

Exposure-Response Safety Analysis - Infections

• Amongst the 217 patients who received SC doses of TECVAYLI, the rates of grade ≥3 infection TEAEs were not associated with concentrations of TECVAYLI when assessed in the predicted exposure quartiles.

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.^4-6,11,26

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.¹¹
• 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.^4,26
• 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.¹¹
• Cohort C: safety, tolerability, and optimal doses.⁴
• Cohort D: safety.⁵
• Cohort E: safety, dose-limiting toxicities, and laboratory abnormalities.⁶

Cohort A

D’Souza et al (2024)¹¹ presented the incidence of infections in Cohort A of the MajesTEC-2 study at a median follow-up of 16.2 months (range, 0.5-34.5).

Results

Safety

• The incidence and types of infections in Cohort A at a median follow-up of 16.2 months (range, 0.5-34.5) are presented in Table: MajesTEC-2 Study (Cohort A): Infections (≥15% Overall).
• One patient died due to pseudomonal bacteremia, and 3 patients died due to COVID-19-related pneumonia.
• No fatal infections were reported following implementation of intensified infection prophylaxis, including emphasis on immunoglobulin (Ig) replacement.

Cohort C

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

Results

Safety

• At a median follow-up of 14.7 months (range, 0.5-22.9), the most frequent any grade infections were COVID-19 and pneumonia reported in 28.6% of patients (n=8), respectively. No dose-limiting toxicities (DLTs) related to infections were reported. See Table: MajesTEC-2 (Cohort C: TECVAYLI and Nirogacestat): Incidence of Infections (≥20% Overall).
• Infection-related deaths were reported in 4 patients (COVID-19, sepsis, septic shock and PJP).
• A single patient discontinued TECVAYLI therapy due to pneumonia.

Cohort D

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

Results

Safety

• At a median follow-up of 10.8 months (range, 1.1-16.8), 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%).

Cohort E

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

Results

Safety

• At a median follow-up of 8.4 months (range, 1.1-12.9), the incidence of ≥1 infections (any grade) were reported in 90.6% of patients (n=29). The incidence of ≥1 grade 3/4 infections were reported in 37.5% of patients (n=12).
• The most common infections (any grade; ≥25%) reported were: COVID-19 (37.5%), upper respiratory infections (31.3%), and pneumonia (25.0%).
  • Among the 12 patients that reported COVID-19 during treatment, 4 patients (33.3%) were not vaccinated.
• Treatment discontinuation: 2 patients discontinued treatment due to an infection-related AE: COVID-19.
• The incidence and types of infections are presented in Table: MajesTEC-2 (Cohort E): Incidence of Infections.
  • Additionally, grade 3/4 AEs for anorectal infection (n=1), gastroenteritis (n=1), Haemophilus infection (n=1), and urinary tract infection (n=1) have been reported.
• Two deaths were reported due to infection-related 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.^15,27

Study Design/Methods

SRI Cohorts

• An SRI period consisting of 3 cohorts was used to establish safety prior to enrolling the randomized phase of the study.²⁷
• Maintenance regimen (2-year fixed duration): patients who achieved a complete response (CR) on Tec-Len after 1-year discontinued TECVAYLI and continued lenalidomide for an additional year.²⁷
• Key eligibility criteria: NDMM, receipt of 4 to 6 cycles of 3- or 4-drug induction therapy (PI and/or immunomodulatory drug ± anti-CD38 antibody), and ASCT (single or tandem ASCT permitted) ± consolidation with PR or better.²⁷
• Primary endpoints: PFS and 12-month minimal residual disease (MRD)-negative CR.²⁷
• Key secondary endpoint: safety.²⁷

Zamagni et al (2024)²⁷ presented the incidence of infections 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).

Results

Safety

• Details on infections are provided in Table: MajesTEC-4/EMN30 Study (SRI Cohorts): Infections.
• One death due to COVID-19-related TEAE was reported in SRI Cohort 2.
• Prophylactic intravenous immunoglobulin (IVIG) replacement was advised to maintain serum IgG levels of ≥400 mg/dL. Prophylaxis for Pneumocystis carinii/Pneumocystis jirovecii pneumonia and herpes zoster reactivation and routine antibiotic and antiviral prophylaxis were recommended.

CLINICAL DATA - MajesTEC-5 study

MajesTEC-5 (GMMG-HD10; DSMM-XX; MMY2003) is an open-label, nonrandomized, phase 2 study assessing the safety and efficacy of TECVAYLI- and TALVEY-based combination regimens in patients with TE-NDMM.^12,13

Study Design/Methods

• Key eligibility criteria: presence of NDMM for which high-dose therapy (HDT) and ASCT were intended as part of the treatment plan, completion of HDT and ASCT within 12 months of induction start and within 6 months of the last ASCT (7 months if consolidation was received), receipt of only 1 prior LOT, and achievement of at least PR as per International Myeloma Working Group (IMWG) 2016 without evidence of progression at the time of enrollment.¹³
• Primary endpoints: safety and tolerability.¹³

Raab et al (2024)¹³ presented the incidence of infections from 3 induction cohorts of the MajesTEC-5 study.

Results

Safety

• Details on infections are provided in Table: MajesTEC-5 Study: Infections (>10% in Any Arm).
• No treatment discontinuations were reported due to infection.
• No grade 5 infections were reported.
• Infection prophylaxis, including Ig replacement, was strongly recommended. Prophylaxis for Pneumocystis jirovecii pneumonia and herpes zoster reactivation and routine antibiotic prophylaxis were recommended.

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.^9,28

Study Design/Methods

SRI Cohort 1 (Tec-DR)

• An SRI period was used to establish safety prior to enrolling the randomized phase of the study.²⁸
• Key eligibility criteria: NDMM either ineligible or not intended for ASCT.^9,28
• Primary endpoints: PFS, 12-month MRD-negative CR.^9,28
• Key secondary endpoint: Safety.^9,28

Touzeau et al (2024)²⁸ 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).

Results

Safety

• The incidence of treatment-emergent infections at a median follow-up of 13.8 months are summarized in Table: MajesTEC-7 SRI Cohort 1 (Tec-DR): Treatment-Emergent Infections.
• Any-grade infections were reported in all patients, with grade 3/4 infections reported in 30.8% of patients. Grade 3/4 infections did not increase with cumulative exposure to Tec-DR and most grade 3/4 infections had first onset within the first 3 treatment cycles.
• One patient discontinued all study treatment due to death in cycle 3 from influenza pneumonia.

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.^7,14,16,29

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.^16,29
• Primary endpoints: dose limiting toxicity and ORR.^16,29

Cohen et al (2025)^16,30 published the incidence of infections 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) cohort and 18.2 months (range, 0.7-27.0) in the recommended phase 2 regimen (RP2R; dose level 5) cohort.

Results

Safety

• Details on infections are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Infections (≥5% Overall).^16,29,30
• Across all dose levels, the incidence of first onset of grade ≥3 infections was higher in the first 6 months of study treatment and then plateaued. The timing of the first onset of grade ≥3 infections is shown in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Timing of First Onset of Grade ≥3 Infections in Patients Across All Dose Levels.^16,30
• Infection prophylaxis was administered as per institutional guidelines. A total of 82% of patients (n=77) across all dose levels received antiviral prophylaxis, and 49% of the patients (n=46) received prophylaxis against Pneumocystis jirovecii pneumonia.^16,30
• In total, 63% of patients (n=59) received a COVID-19 vaccine.¹⁶
• Immunoglobulin replacement therapy (0.4 g/kg every 3-6 weeks) was recommended to maintain serum immunoglobulin G (IgG) levels above 400 mg/dL, regardless of current or past infections, with monitoring recommended at least every 3 months after reaching steady state.³⁰
• Immunoglobulin replacement was provided per institutional guidelines for managing serious, recurrent, or chronic infections.³⁰
• Deaths due to infections were reported in 11.7% of patients (n=11) in the all dose levels cohort and 6.8% of patients (n=3) in the RP2R cohort.^16,30

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 DARZALEX FASPRO regimens in combination with bispecific T-cell redirection antibodies in patients with RRMM.^8,11,31

Study Design/Methods

• Key eligibility criteria: ≥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 allowed, prior BsAb and CAR-T were allowed.⁸
• Key primary endpoint: safety.^8,11,31

D'Souza et al (2024)¹¹ presented the incidence of infections in the TECVAYLI + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 38.3 months (range, 1.2-39.6).

Results

Safety

• The incidence and types of infections at a median follow-up of 38.3 months (range, 1.2-39.6) are presented in Table: TRIMM-2 Study (TECVAYLI + DARZALEX FASPRO + Pomalidomide Cohort): Infections.
• Deaths due to infection were reported in 2 patients, 1 due to pneumonia and 1 due to COVID-19 pneumonia.
• No fatal infections occurred following implementation of intensified infection prophylaxis, including emphasis on Ig replacement.

Rodriguez-Otero et al (2022)⁸ presented the incidence of infections in 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).

Results

Safety

• At a median follow-up of 8.6 months (range, 0.3-19.6), infections were reported in 44 patients (67.7%); 27.7% of infections were grade 3/4.
• Three infection-related deaths have been reported (bacterial pneumonia, sepsis, 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 04 February 2025.