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.
• CRS has 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.^1-12
• 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).^1-3,10,13-15
  • 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
    • At a median follow-up of 14.1 months (range, 0.3-24.4), CRS of any grade occurred in 72.1% of patients (n=119); Grade 3 CRS with concurrent pneumonia occurred in 1 patient (0.6%). The overall median time to CRS onset was 2 days (range, 1-6). The median duration of CRS was 2 days (range, 1-9).^1,16
    • At a longer-term median follow-up of 30.4 months, no changes in CRS were reported.¹³
  • Catamero et al (2023) presented the nursing experience at the Mount Sinai Health System with TECVAYLI in the MajesTEC-1 study of monitoring, managing, and educating of CRS.¹⁷
  • 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.^10,18 Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
    • At a median follow-up of follow-up of 28.0 months (range, 0.7-31.1), CRS events of any grade were reported in 65% of patients (n=26) overall. The median time to CRS onset was 2 days (range, 2-6). The median duration of CRS was 2 days (range, 1-4).¹⁰
  • The prophylactic tocilizumab cohort is evaluating the administration of intravenous (IV) tocilizumab (8 mg/kg) prior to TECVAYLI dosing for the reduction of CRS in 24 patients with RRMM.^3,19 Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
    • At a median follow-up of 2.6 months (range, 0.1-7.0), 23 patients received prophylactic tocilizumab prior to TECVAYLI. CRS occurred in 26.1% of patients (n=6). All CRS events were Grade 1/2. The median time to CRS onset was 2.0 days (range, 1-3). The median duration of CRS was 2.0 days (range, 2-4).³
    • At a longer median follow-up of 8.1 months (range, 0.9-13.2), 24 patients received prophylactic tocilizumab prior to TECVAYLI. CRS occurred in 25% of patients (n=6). All CRS events were Grade 1/2 in severity. The median time to CRS onset was 2.0 days (range, 1-3). The median duration of CRS was 2.0 days (range, 2-4).¹⁹
• 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).^4-6,20 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 is assessing the safety and efficacy of TECVAYLI in combination with DARZALEX FASPRO and pomalidomide in 27 patients with RRMM.²¹
    • At a median follow-up of 16.2 months (range, 0.5-34.5), CRS of any grade was reported in 47.1% of patients (n=8). All CRS events were grade 1/2 and resolved.²¹
  • Cohort C is evaluating the safety and efficacy of TECVAYLI in combination with nirogacestat in 28 patients with RRMM.⁴
    • At a median follow-up of 14.7 months (range, 0.5-22.9), CRS of any grade was reported in 75% of patients (n=21). One Grade 3 CRS event was reported at dose level 1 (concurrent nirogacestat). 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).⁴
  • Cohort D is evaluating the safety and efficacy of TECVAYLI in combination with lenalidomide (Tec-Len) in 31 patients with triple-class exposed MM.⁵
    • At a median follow-up of 10.8 months (range, 1.1-16.8), CRS of any grade occurred in 67.7% of patients (n=21). One Grade 3 CRS event occurred that was associated with Grade 3 hypotension during the TECVAYLI step-up dose (SUD) 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).⁵
  • Cohort E is evaluating the safety and efficacy of the combination of TECVAYLI with DARZALEX FASPRO and lenalidomide (Tec-DR) in 32 patients.⁶
    • At a median follow-up of 8.4 months (range, 1.1-12.9), CRS of any grade occurred in 81.3% of patients (n=26). Grade 3/4 CRS have not been reported. The median time to onset of CRS was 2 days (range, 1-8). The median duration of CRS was 2 days (range, 1-22).⁶
• 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).^11,22 Janssen does not recommend the use of TECVAYLI or lenalidomide in a manner that is inconsistent with the approved labeling.
  • A Safety run-in (SRI) cohort is evaluating preliminary safety and efficacy results from SRI Cohort 1 (Tec-Len; TECVAYLI weekly [QW] to once every 4 weeks [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).¹¹
    • Any-grade CRS was reported in 50% of patients (n=16) in Cohort 1, 40.6% of patients (n=13) in Cohort 2, and 43.3% of patients (n=13) in Cohort 3. All events were grade 1/2.¹¹
• 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).^12,23 Janssen does not recommend the use of TECVAYLI or TALVEY in a manner that is inconsistent with the approved labeling.
  • Three induction cohorts of the MajesTEC-5 study are evaluating initial safety and efficacy results from arm A (Tec [QW]-DR; n=10), arm A1 (Tec [Q4W]-DR; n=20), and arm B (TECVAYLI Q4W in combination with DARZALEX FASPRO, bortezomib, and lenalidomide; Tec [Q4W]-DVR; n=19).¹²
    • Any-grade CRS was reported in 65.3% of patients (n=32) overall; 60% of patients (n=6) in arm A, 70% of patients (n=14) in arm A1, and 63.2% of the patients (n=12) in arm B. All events were grade 1/2. Most CRS events occurred in cycle 1.¹²
• 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.^9,24 Janssen does not recommend the use of TECVAYLI, TALVEY or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
  • SRI Cohort 1 is evaluating the initial safety results of Tec-DR in 26 patients.²⁴
    • At a median follow-up of 13.8 months (range, 2.0-15.4), CRS of any grade occurred in 61.5% of patients (n=16), with Grade 1 CRS occurring in 57.7% of patients and Grade 2 CRS occurring in 3.8% of patients. Most events occurred in Cycle 1 of treatment. All cases resolved.²⁴
• RedirecTT-1 (MMY1003) is an ongoing, open-label, phase 1b study evaluating the safety and efficacy of TALVEY and TECVAYLI combination in patients with RRMM.^7,25,26Janssen does not recommend the use of TALVEY and TECVAYLI in a manner inconsistent with the approved labeling.
  • The TALVEY and TECVAYLI cohort is evaluating the safety and efficacy of the combination in 94 patients at all dose levels and in 44 patients at the recommended phase 2 regimen (RP2R), including in patients with extramedullary disease (EMD).²⁶
    • All dose levels (N=94): At a median follow-up of 20.3 months, CRS was reported in 78.7% of patients (n=74). The median time to onset of CRS was 2 days (range, 1-733). The median duration of CRS was 2 days (range, 1-8).²⁶
    • Recommended phase 2 regimen (RP2R; n=44): At a median follow-up of 18.2 months (range, 0.7-27.0), CRS was reported in 75.0% of patients (n=33). The median time to onset of CRS was 2 days (range, 1-4). The median duration of CRS was 2 days (range, 1-5).²⁶
• 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.^8,21,27 Janssen does not recommend the use of TECVAYLI or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
  • The TECVAYLI + DARZALEX FASPRO ± pomalidomide cohort is evaluating the safety and efficacy of the combination in 10 patients.²¹
    • At a median follow-up of 38.3 months (range, 1.2-39.6), any-grade CRS was reported in 70% of patients (n=7). All CRS events were grade 1/2 and resolved.²¹
  • The TECVAYLI + DARZALEX FASPRO cohort is evaluating the safety and efficacy of the combination in 65 patients.⁸
    • At a median follow-up of 8.6 months (range, 0.3-19.6), CRS occurred in 67.7% of patients (n=44). All CRS events were Grade 1/2. The median time to onset of CRS (relative to the most recent dose) was 2.5 days (range, 1-7). The median duration of CRS was 2.0 days (range, 1-7).⁸

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.^1-3,10,13-15

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 of TECVAYLI at the RP2D; and Part 3 (phase 2 component) to evaluate the safety and efficacy of TECVAYLI at the RP2D.^1,28
• 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.^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 therapy 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
• Per protocol, participants with any CRS were summarized by the maximum toxicity grades according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading system. CRS symptoms and events were captured as AEs of special interest.²⁸
• Prior to the administration of TECVAYLI, during the step-up dosing schedule or following dose interruption, CRS, including fever, was required to be completely resolved. Additionally, patients must not have had any evidence of serious viral, fungal, or bacterial infection to avoid worsening CRS.²⁹
• For the overall study population (phase 1/2), the time to onset and duration of CRS was determined in days. For the phase 2 portion, the time to onset and duration of CRS was determined in hours.²⁹
• Prior to the first TECVAYLI dose, a serum sample was utilized to assess sBCMA. Prior to the first SUD and after select step-up and/or treatment doses, peripheral serum or whole blood was collected to assess cytokines and T-cell activation, respectively.²⁹
• Per protocol, growth factor support was to be avoided during SUD, first treatment dose and during CRS.²⁸
• Prophylactic tocilizumab cohort: CRS as an AE was graded as per the criteria by Lee et al. CRS management with tocilizumab treatment was permitted for grade 1 CRS and was recommended for grade ≥2 CRS.¹⁹

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

Cohort A

• A total of 165 patients were enrolled in the RP2D cohort; 40 patients were enrolled in phase 1 and 125 patients were enrolled in phase 2. At a median follow-up of 30.4 months, 65 patients had transitioned to less frequent dosing (eg, every other week [Q2W]). At the data cutoff of August 22, 2023, 38 patients remained on treatment (37 remained on less frequent dosing schedule).^1,13

Cohort C

• At a median follow-up of 28.0 months (range, 0.7-31.1), 40 patients had received TECVAYLI with a median duration of treatment of 6.0 months (range, 0.2-29.8).¹⁸
• All patients in Cohort C were triple-class exposed (PI, immunomodulatory drug, anti-CD38 monoclonal antibody). All patients were exposed to BCMA-targeted treatment (72.5% of patients [n=29] were exposed to ADC therapy and 37.5% of patients [n=15] were exposed to CAR-T therapy). There were 4 patients who previously received both BCMA-targeted therapies.¹⁰
• At baseline, patients received a median of 6 prior LOTs (range, 3-14), 85.0% of patients (n=34) were refractory to the last LOT, 85.0% of patients (n=34) were triple-class refractory and 35.0% of patients (n=14) were penta-drug refractory.¹⁸

Prophylactic Tocilizumab Cohort

• At a median follow-up of 2.6 months (range, 0.1-7.0), 23 patients received prophylactic tocilizumab prior to the first TECVAYLI SUD.¹⁹
• At a longer median follow-up of 8.1 months (range, 0.9-13.2), 24 patients received prophylactic tocilizumab prior to the first TECVAYLI SUD.¹⁹
• Patients received a median of 4 prior LOTs (range, 2-9).¹⁹

Safety - Adverse Event - CRS

Cohort A

Median Follow-up: 14.1 Months

• At a median follow-up of 14.1 months (range, 0.3-24.4) a total of 195 CRS events occurred in 119 patients (72.1%). Details are summarized Tables: MajesTEC-1 Study (Cohort A): Overall Characteristics and Management of CRS and MajesTEC-1 Study (Cohort A): Incidence of CRS by Grade and Timing.^1,29
  • After the first treatment cycle, CRS events were reported in 6 of 119 patients (5%); all 6 patients had prior CRS events (4 patients had Grade 1 CRS, 1 patient had Grade 2 CRS and 1 patient had Grades 1 and 3 CRS).²⁹
    • Subsequent Grade 1 CRS events occurred in 3 patients on Cycle 2 Day 1 (1 of the 3 patients had a urinary tract infection 1 week earlier) and in a fourth patient on Cycle 2 Days 1 and 8. A fifth patient experienced Grade 1 CRS after repeat step-up dosing before Cycle 6 (this patient had a 6-week interruption in TECVAYLI treatment at the end of Cycle 5 due to Pseudomonas aeruginosa and Clostridium difficile infections); the patient had another Grade 1 CRS event on Cycle 6 Day 1. Grade 1 CRS was also reported in a sixth patient at SUD 1 followed by a Grade 3 CRS event with concurrent Grade 3 pneumonia after Cycle 1 Day 1. Treatment with TECVAYLI for this patient was interrupted until the pneumonia resolved and was restarted 5 weeks later with repeat step-up dosing. The patient experienced 2 subsequent Grade 2 CRS events (after repeat SUD 2 before Cycle 2 and on Cycle 3 Day 8 at the time of disease progression).²⁹
  • After subsequent TECVAYLI doses, 55 patients experienced recurrent CRS events out of the 119 patients with CRS events. Of these, 4 patients had a worse CRS grade in their subsequent event (3 patients had Grade 1 CRS followed by Grade 2 CRS and 1 patient had Grade 1 CRS followed by Grade 3 CRS). The recurrence of subsequent CRS events by grade is presented in Table: MajesTEC-1 Study (Cohort A): Recurrent CRS Events by Grade After Subsequent Doses.²⁹
  • The median time to onset (relative to the most recent TECVAYLI dose) was 2 days (range, 1-6) with a median duration of 2 days (range, 1-9) for the overall study.¹
  • For the phase 2 part of the study, the median time to onset of CRS (relative to the most recent TECVAYLI dose) was 31.13 hours (range, 3.83-120.50), with a median duration of 11.79 hours (0.33-151.05).²⁹
  • All CRS events resolved without discontinuation of treatment.²⁹

Subsequent CRS Events After Management of First CRS Event

• Of the 119 patients with CRS, patients who experienced a subsequent CRS event after management of the first CRS event is presented in Table: MajesTEC-1 Study (Cohort A): Occurrence of Subsequent CRS Events in Patients Managed With Tocilizumab and/or Steroids.²⁹
  • The median duration of a CRS event was 2 days in the 60 patients managed with tocilizumab. Median time from the start of a CRS event to administration of tocilizumab was 1 day (range, 1-9) and median time from administration of tocilizumab to resolution of CRS was 1 day (range, 1-5).²⁹
• A total of 195 CRS events were reported, of which 68 events were managed with tocilizumab. CRS events managed with tocilizumab are summarized in the Table: MajesTEC-1 Study (Cohort A): CRS Events and Subsequent CRS Events by Grade According to Management With Tocilizumab.²⁹
  • Forty-five patients received tocilizumab for their first CRS event. Of these, 9 patients (20%) had a subsequent CRS event. A subsequent CRS event was reported in 46 of 74 patients (62%) who were not managed with tocilizumab for their first CRS event.²⁹

Incidence and Severity of CRS Events by Baseline Characteristics

• The incidence of CRS by baseline tumor characteristics is presented in Table: MajesTEC-1 Study (Cohort A): Incidence of CRS by Baseline Tumor Burden and Tumor BCMA Expression.³⁰
• Baseline cytokine levels were not found to be associated with CRS incidence or grade.²⁹
• No apparent relationship between patient baseline characteristics and CRS severity or incidence was observed.²⁹

Median Follow-up: 30.4 Months

• At a longer-term median follow-up of 30.4 months, no changes in CRS were reported.¹³

Prophylactic Tocilizumab Cohort

Median Follow-up: 2.6 Months

• Among the 23 patients who received prophylactic tocilizumab, 6 patients (26.1%) experienced CRS. See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): CRS Incidence and Severity for additional details.³
• The median time to CRS onset was 2.0 days (range, 1-3). The median duration of CRS was 2.0 days (range, 2-4).³
• Tocilizumab was used after the first CRS event in 4 patients, with 1 patient also receiving dexamethasone.³
• All CRS events resolved without treatment discontinuation.³
• All CRS events occurred during step-up dosing schedule through Cycle 2. See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): CRS Incidence and Baseline Characteristics for additional details.³
• An association was not clearly observed between the occurrence of CRS of any grade and patient or disease characteristic. See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): CRS by Grade and Baseline Characteristics for additional details.³

Median Follow-up: 8.1 Months

• Among the 24 patients who received prophylactic tocilizumab, 25% experienced CRS. See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): CRS Incidence and Severity for additional details.¹⁹
  • All initial CRS events occurred during TECVAYLI step-up dosing 1 and 2. The median time to CRS onset was 2 days (range, 1-3). The median duration of CRS was 2 days (range, 2-4).¹⁹
  • A total of 3 patients each had 1 recurrent CRS event.¹⁹
  • All CRS events resolved.¹⁹
  • There was no observed association between CRS and any specific patient disease or patient characteristic. See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): CRS by Grade and Baseline Characteristics for additional details.¹⁹
• The magnitude of IL-6 induction was higher with prophylactic tocilizumab. Based on modeling data, a single tocilizumab dose inhibits IL-6 signaling for approximately 10 days and the duration of IL-6 blockage spans the TECVAYLI dosing schedule.¹⁹

Correlative Analysis: MajesTEC-1 Study

Cortes-Selva et al (2022)³¹ conducted correlative analyses to evaluate the relationship between immune status and response to TECVAYLI. These analyses assessed baseline immune and tumor correlatives with outcomes in patients who received TECVAYLI in the MajesTEC-1 study.

Methods

• The following biological correlatives were evaluated: T-cell numbers and subsets, regulatory T cells (Tregs), markers of T-cell exhaustion, baseline BCMA expression, and sBCMA levels. These biological correlatives were investigated for their respective clinical impact on CRS, clinical response, high-risk characteristics, and progression-free survival (PFS). Unless other specified, Wilcoxon rank sum tests were performed.
• The analyses were conducted by collecting whole blood samples, bone marrow aspirates, and serum samples from patients treated at the RP2D and other active doses (IV and subcutaneous [SC] doses with partial response [PR] or better) of TECVAYLI. These collected samples were analyzed by flow cytometry, cytometry by time of flight, or electroluminescence assays.
  • Doses of TECVAYLI: RP2D of 1.5 mg/kg SC with 0.06 and 0.3 mg/kg SUDs; IV active doses of 0.72 mg/kg QW with SUDs and SC active doses of 0.72-6 mg/kg Q2W with SUDs.

Observations

• These correlative analyses observed quantitative and qualitative aspects of T cells, as well as various T cells subsets in association with clinical determinants such as CRS, clinical response, high-risk characteristics, and PFS.
• Figure: Baseline sBCMA Levels and T-cell Characteristics, shows the following observations: at baseline, CRS occurrence was related to lower frequencies of CD4 T-cells expressing TIM-3 and PD-1/TIM-3 and higher frequencies of CD3 T cells. High sBCMA levels were not correlated with an increased risk of CRS.

CLINICAL DATA - MajestEC-2 STudy

MajesTEC-2 (MMY1004; clinicaltrials.gov identifier: 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.²⁰

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.²¹
• Cohort C (TECVAYLI and nirogacestat): disease progression within 12 months of the 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.^4,20
• Cohort D (Tec-Len): received ≥2 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, and no prior BCMA-targeted therapy.⁵
• Cohort E (Tec-DR): received 1 to 3 prior LOTs, including a PI, and an immunomodulatory drug, and no prior BCMA-targeted therapy.⁶

Primary Endpoints

• Cohort A: safety and dose-limiting toxicities.²¹
• Cohort C: safety, tolerability, and optimal doses.⁴
• Cohort D: safety.⁵
• Cohort E: safety, dose-limiting toxicities, and laboratory abnormalities.⁶

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

Cohort A

• A total of 17 patients received TECVAYLI in combination with DARZALEX FASPRO and pomalidomide.²¹
• Patients received a median of 1 prior LOT (range, 1-4). None of the patients were triple-class refractory; furthermore, 17.6% of patients (n=3) received prior anti-CD38 therapy.²¹

Cohort C

• Patients received a median of 4 prior LOTs (range, 2-12), 92.9% of patients (n=26) were refractory to the last LOT, 71.4% of patients (n=20) were triple-class refractory, and 21.4% of patients (n=6) were penta-drug refractory.⁴

Cohort D

• A total of 31 patients were administered Tec-Len. Twelve patients received TECVAYLI 0.72 mg/kg with lenalidomide 25 mg and 19 patients received TECVAYLI 1.5 mg/kg with lenalidomide 15 mg.⁵
• Patients received a median of 4 prior LOTs (range, 2-9). All patients were exposed to prior lenalidomide, 41.9% of patients (n=13) were refractory to lenalidomide, 41.9% of patients (n=13) were triple-class refractory, and 12.9% of patients (n=4) were penta-drug refractory.⁵

Cohort E

• All patients in the cohort were treated with DARZALEX FASPRO and lenalidomide; 19 patients received TECVAYLI 1.5 mg/kg and 13 patients received TECVAYLI 0.72 mg/kg.⁶
• Patients received a median of 2 prior LOTs (range, 1-3). All patients were exposed to prior PI and immunomodulatory drug therapy; 5 patients in each TECVAYLI dose group received prior anti-CD38 antibody therapy.⁶

Safety - Adverse Event - CRS

Cohort A

• At a median follow-up of 16.2 months (range, 0.5-34.5), CRS of any grade was reported in 47.1% of patients (n=8). All CRS events were grade 1/2 and resolved.²¹

Cohort C

• At a median follow-up of 14.7 months (range, 0.5-22.9), CRS events of any grade occurred in 75.0% of patients (n=21). A Grade 3 CRS event occurred in a patient at dose level 1. The incidence and management of CRS events are summarized in Table: MajesTEC-2 (Cohort C: TECVAYLI + nirogacestat): Incidence and Management of CRS.⁴
• 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 cutoff.⁴

Cohort D

• At a median follow-up 10.8 months (range, 1.1-16.8), CRS events of any grade occurred in 67.7% of patients (n=21).⁵
• All CRS events occurred during TECVAYLI step-up dosing through Cycle 2 (one subsequent CRS event occurred during Cycle 2).⁵
• 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).⁵

Cohort E

• At a median follow-up of 8.4 months (range, 1.1-12.9), CRS AEs (any grade) occurred in 26 patients (81.3%). The incidence and management of CRS are presented in Table: MajesTEC-2 (Cohort E: TECVAYLI + DARZALEX FASPRO + lenalidomide): Characteristics and Management of CRS.⁶
• The median time to onset of CRS was 2 days (range, 1-8). The median duration was 2 days (range, 1-22). Note: the median duration range was confounded by ongoing infection.⁶
• Of the 38 CRS events, 37 (97%) events were reported during Cycle 1.⁶

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.^11,22

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.¹¹
• 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.¹¹
• Key eligibility criteria: NDMM, receipt of 4 to 6 cycles of 3- or 4-drug induction therapy (PI ± immunomodulatory drug ± anti-CD38 antibody), and ASCT (single or tandem ASCT permitted) ± consolidation with PR or better.¹¹
• Primary endpoints: PFS and 12-month minimal residual disease (MRD)-negative CR.¹¹
• Key secondary endpoint: safety.¹¹

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• The median follow-up was 21.1 months (range, 14.8-23.8) for SRI Cohort 1 (Tec-Len; TECVAYLI QW to Q4W; N=32), 9.2 months (range, 1.2-12.2) for SRI Cohort 2 (Tec-Len; TECVAYLI Q4W; N=32), and 9.2 months (range, 3.7-11.5) for SRI Cohort 3 (TECVAYLI Q4W; N=30).¹¹
• The median time from ASCT to enrollment for all patients was 4.7 months (range, 1.8- 7.4).¹¹
• Prior consolidation was reported in 18.8% of patients (n=6) in Cohort 1, 37.5% of patients (n=12) in Cohort 2, and 33.3% of patients (n=10) in Cohort 3.¹¹

Safety - Adverse Event - CRS

• Any-grade CRS was reported in 50% of patients (n=16) in Cohort 1, 40.6% of patients (n=13) in Cohort 2, and 43.3% of patients (n=13) in Cohort 3. All events were grade 1/2.¹¹
• The incidence of CRS was 37.2% after SUD 1, 8.5% after SUD 2, and 5.3% after treatment dose 1.¹¹
• No discontinuations were reported due to CRS.¹¹

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.^12,23

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 a PR as per International Myeloma Working Group (IMWG) 2016 criteria without evidence of progression at the time of enrollment.¹²
• Primary endpoints: safety and tolerability.¹²

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 49 patients (n=10, arm A; n=20, arm A1; and n=19, arm B) were included in the study.¹²
• Stem cell mobilization was feasible with Tec-DR and Tec-DVR, yielding a median number of 8.4×10⁶/kg CD34-positive cells across the study arms.¹²

Safety - Adverse Event - CRS

• Any-grade CRS was reported in 65.3% of patients (n=32) overall; 60% of patients (n=6) in arm A, 70% of patients (n=14) in arm A1, and 65.3% of patients (n=32) in arm B. All events were grade 1/2. Most CRS events occurred in cycle 1.¹²
• All CRS events resolved with no treatment discontinuation due to CRS events.¹²

CLINICAL DATA - MajesTEC-7 study

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.^9,24

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.²⁴
• Key eligibility Criteria: NDMM either ineligible or not intended for ASCT.^9,24
• Primary endpoints: PFS, 12-month MRD-negative CR.^9,24
• Key Secondary endpoint: safety.^9,24

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

SRI Cohort 1

• At a median follow-up of 13.8 months (range, 2.0-15.4), 26 patients received a median of 15 cycles (range, 2-17) of Tec-DR.²⁴
• Median relative-dose intensity was 97% for TECVAYLI, 95.8% for DARZALEX FASPRO, and 58.6% for lenalidomide, with 17 patients undergoing dose reduction.²⁴

Safety - Adverse Event - CRS

SRI Cohort 1

• At a median follow-up of 13.8 months (range, 2.0-15.4), CRS of any grade occurred in 61.5% of patients (n=16), with Grade 1 CRS occurring in 57.7% of patients and Grade 2 CRS occurring in 3.8% of patients. Most events occurred in Cycle 1 of treatment. All cases resolved.²⁴

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

RedirecTT-1, (MMY1003; clinicaltrials.gov identifier: NCT04586426) is an ongoing, open-label, phase 1b evaluating the safety and efficacy of the combination of TALVEY and TECVAYLI in patients with RRMM.^7,25,26

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.⁷
• Primary endpoints: safety, identify RP2R(s), and schedule.^7,26

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• The median duration of follow-up was 20.3 months in the all dose levels cohort and 18.2 months (range, 0.7-27.0) in the RP2R cohort.²⁶
• All dose levels (N=94): Patients received a median of 4 prior LOTs (range, 1-11), 92.6% of patients (n=87) were refractory to the last LOT, 86.2% of patients (n=81) were triple-class refractory.²⁶
• RP2R (n=44): Patients received a median of 4 prior LOTs (range, 2-10), 88.6% of patients (n=39) were refractory to the last LOT, 84.1% of patients (n=37) were triple-class refractory.²⁶

Safety - Adverse Event - CRS

• Details on CRS occurrence and management are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Incidence and Management of CRS.²⁶
• Most CRS events occurred during step-up dosing and Cycle 1 Day 1 doses. All CRS events recovered.²⁶

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.^8,27

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.⁸
• Key primary endpoint: safety.^8,21,27

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

TECVAYLI + DARZALEX FASPRO + Pomalidomide Cohort

• A total of 10 patients were administered the TECVAYLI + DARZALEX FASPRO + pomalidomide combination.²¹
• Patients received a median of 4 prior LOTs (range, 3-16); 80% of patients (n=8) received prior anti-CD38 therapy, 30% of patients (n=3) received prior BCMA-targeted therapy, and 70% of patients (n=7) were triple-class refractory.²¹

TECVAYLI + DARZALEX FASPRO Cohort

• A total of 65 patients received the TECVAYLI and DARZALEX FASPRO combination.⁸
• Patients received a median of 5 prior LOTs (range, 1-15), 80% of patients were refractory to the last LOT, 58.5% of patients were triple-class refractory and 30.8% of patients were penta-drug refractory.⁸

Safety - Adverse Event - CRS

TECVAYLI + DARZALEX FASPRO + Pomalidomide Cohort

• At a median follow-up of 38.3 months (range, 1.2-39.6), any-grade CRS was reported in 70% of patients (n=7); all CRS events were grade 1/2 and resolved.²¹

TECVAYLI + DARZALEX FASPRO Cohort

• At a median follow-up of 8.6 months (range, 0.3-19.6), CRS events occurred during SUDs or the first full treatment dose. All CRS events were Grade 1/2 and resolved without stopping treatment.⁸
• The median time to CRS onset (relative to most recent dose) was 2.5 days (range, 1-7). The median duration of CRS was 2.0 days (range, 1-7).⁸
• The incidence, and management of CRS are detailed in Table: TRIMM-2 Study (TECVAYLI + DARZALEX FASPRO Cohort): Characteristics and Management of CRS.⁸

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 15 January 2025.