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.
• Injection site reactions have been reported as adverse events in the MajesTEC-1, MajesTEC-2, MajesTEC-4, MajesTEC-7, and TRIMM-2 studies.^1-6
• 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).^1,3,7-10
  • 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
    • Moreau et al (2022)¹ published the incidence of injection site reactions at a median follow-up of 14.1 months (range, 0.3-24.4). Injection site reactions were reported in 36.4% of patients (n=60); all events were grade 1/2.
    • van de Donk et al (2023)⁸ presented the incidence of injection site reactions at a median follow-up of 23 months. Injection site erythema of any grade was reported in 26.1% of patients (n=43). No grade 3/4 injection site erythema was reported.
    • Garfall et al (2024)⁹ presented the incidence of injection site reactions at a longer-term median follow-up of 30.4 months. Injection site erythema was reported in 26.7% of patients overall (n=44). No grade 3/4 injection site erythema was reported.
  • 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.^10,11 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 injection site reactions at a median follow-up of 28.0 months (range, 0.7-31.1). Injection site erythema was reported in 32.5% of patients (n=13); all events were grade 1/2. Injection site pruritus was reported in 15.0% of patients (n=6); all events were grade 1/2.
• 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).^2,5,12 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.⁵
    • D’Souza et al (2024)⁵ presented incidence of injection site reactions at a median follow-up of 16.2 months (range, 0.5-34.5). Injection site erythema of any grade was reported in 41.2% of patients (n=7). No grade 3/4 injection site erythema was reported.
  • Cohort C included 28 patients with RRMM who received TECVAYLI and nirogacestat.^2,12
    • Offner et al (2023)¹² presented the incidence of injection site reactions at a median follow-up of 14.7 months (range, 0.5-22.9). Injection site erythema of any grade was reported in 53.6% of patients (n=15). No grade 3/4 injection site erythema was reported.
• MajesTEC-4 (EMN30; MMY3003) is an open-label, randomized, multicenter, phase 3 study assessing the safety and efficacy of TECVAYLI in combination with lenalidomide (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).^6,13 Janssen does not recommend the use of TECVAYLI or lenalidomide in a manner that is inconsistent with the approved labeling.
  • Zamagni et al (2024)⁶ presented the incidence of injection site reactions 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), injection site erythema of any grade was reported in 21.9% of patients (n=7). No grade 3/4 injection site erythema was reported.
    • Cohort 2 (Tec-Len; TECVAYLI Q4W; N=32): At a median follow-up of 9.2 months (range, 1.2-12.2), injection site erythema of any grade was reported in 37.5% of patients (n=12). No grade 3/4 injection site erythema was reported.
    • Cohort 3 (TECVAYLI Q4W; N=30): At a median follow-up of 9.2 months (range, 3.7-11.5), injection site erythema of any grade was reported in 26.7% of patients (n=8). No grade 3/4 injection site erythema was reported.
• MajesTEC-7 (MMY3005) is a randomized, phase 3, open-label, multicenter study comparing the safety and efficacy of TECVAYLI in combination with DARZALEX FASPRO and lenalidomide (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.^4,14 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)¹⁴ presented the incidence of injection site reactions from SRI Cohort 1 (Tec-DR) at a median follow-up of 13.8 months (range, 2.0-15.4). Injection site erythema of any grade was reported in 34.6% of patients (n=9). No grade 3/4 injection site erythema was reported.
• 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.^5,15,16 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)⁵ presented the incidence of injection site reactions in the TECVAYLI + DARZALEX FASPRO + pomalidomide cohort (N=10) at a median follow-up of 38.3 months (range, 1.2-39.6). Injection site erythema of any grade was reported in 30% of patients (n=3). No grade 3/4 injection site erythema was reported.
• Other relevant literature has been identified in addition to the data summarized above.
  • Yoon et al (2024)¹⁷ published a case report describing a patient who developed an injection site reaction following TECVAYLI administration.

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 study (MMY1001; clinicaltrial.gov identifiers: NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.^1,3,7,8,10

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.^1,18

• 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.^1,8
  • 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
• Primary endpoint for Cohort A and Cohort C: overall response rate (ORR).^1,8,10
• Key secondary endpoint for Cohort A and Cohort C: safety.^1,8,10

Cohort A

Moreau et al (2022)¹ published the incidence of injection site reactions at a median follow-up of 14.1 months (range, 0.3-24.4).

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• 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.
• Patients received a median of 5 prior LOTs (range, 2-14); 89.7% were refractory to the last LOT, 77.6% were triple-class refractory, and 30.3% were penta-drug refractory.

Safety

• At a median follow-up of 14.1 months (range, 0.3-24.4), injection site reactions were reported in 36.4% of patients (n=60); all events were grade 1/2.

van de Donk et al (2023)⁸ presented the incidence of injection site reactions at a median follow-up of 23 months.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• At a median follow-up of 23 months, 47 patients remained on treatment.

Safety

• At a median follow-up of 23 months, injection site erythema of any grade was reported in 26.1% of patients (n=43). No grade 3/4 injection site erythema was reported.⁸

Garfall et al (2024)⁹ presented the incidence of injection site reactions at a longer-term median follow-up of 30.4 months.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• At a median follow-up of 30.4 months, 165 patients had received TECVAYLI at the RP2D. Of these, 65 patients transitioned to less frequent dosing (eg, every 2 weeks [Q2W]).
  • At the data cutoff of August 22, 2023, 38 patients remained on treatment (37 remained on a less frequent dosing schedule).

Safety

• At a median follow-up of 30.4 months, injection site erythema was reported in 26.7% of patients overall (n=44). No grade 3/4 injection site erythema was reported.

Cohort C

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

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• 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).
• All patients in Cohort C were triple-class exposed (PI, immunomodulatory drug, anti-CD38 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.
• At baseline, patients received a median of 6 prior LOTs (range, 3-14), 85.0% were refractory to the last LOT, 85.0% were triple-class refractory and 35.0% were penta-drug refractory.

Safety

• At a median follow-up of 28.0 months (range, 0.7-31.1), injection site erythema was reported in 32.5% of patients (n=13); all events were grade 1/2. Injection site pruritus was reported in 15.0% of patients (n=6); all events were grade 1/2.

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.^5,12,19

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.⁵
• 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.^12,19

Primary Endpoints

• Cohort A: safety and dose-limiting toxicities.⁵
• Cohort C: safety, tolerability, and optimal doses.¹²

Cohort A

D’Souza et al (2024)⁵ presented the incidence of injection site reactions in Cohort A of the MajesTEC-2 study at a median follow-up of 16.2 months (range, 0.5-34.5).

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 17 patients received TECVAYLI in combination with DARZALEX FASPRO and pomalidomide.
• 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.

Safety

• At a median follow-up of 16.2 months (range, 0.5-34.5), injection site erythema of any grade was reported in 41.2% of patients (n=7). No grade 3/4 injection site erythema was reported.

Cohort C

Offner et al (2023)¹² presented the incidence of injection site reactions at a median follow-up of 14.7 months (range, 0.5-22.9).

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• Among the 28 patients treated with TECVAYLI and nirogacestat: at dose level 1, 8 patients received TECVAYLI and concurrent nirogacestat; at dose level 2, 7 patients received TECVAYLI and delayed nirogacestat administration; at dose level 3, 13 patients received TECVAYLI and delayed nirogacestat administration.
• 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.

Safety

• At a median follow-up of 14.7 months (range, 0.5-22.9), injection site erythema of any grade was reported in 53.6% of patients (n=15). No grade 3/4 injection site erythema was reported.

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.^6,13

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.⁶
• 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.⁶
• 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 partial response (PR) or better.⁶
• Primary endpoints: progression-free survival (PFS) and 12-month minimal residual disease (MRD)-negative CR.⁶
• Key secondary endpoint: safety.⁶

Zamagni et al (2024)⁶ presented the incidence of injection site reactions 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

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 32 patients were included in SRI Cohort 1, 32 patients in SRI Cohort 2, and 30 patients in SRI Cohort 3.
• The median time from ASCT to enrollment for all patients was 4.7 months (range, 1.8-7.4).
• 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.

Safety

• Any-grade injection site erythema was reported in 21.9% of patients (n=7) in Cohort A, 37.5% of patients (n=12) in Cohort B, and 26.7% of patients (n=8) in Cohort C. No grade 3/4 injection site erythema was reported.

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.^4,14

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.¹⁴
• Key eligibility criteria: NDMM either ineligible or not intended for ASCT.^4,14
• Primary endpoints: PFS, 12-month MRD-negative CR.^4,14
• Key secondary endpoint: Safety.^4,14

Touzeau et al (2024)¹⁴ 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

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• 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.
• Median relative dose intensity was 97% for TECVAYLI, 95.8% for DARZALEX FASPRO, and 58.6% for lenalidomide, with 17 patients undergoing dose reduction.

Safety

• At a median follow-up of 13.8 months, injection site erythema of any grade was reported in 34.6% of patients (n=9). No grade 3/4 injection site erythema was reported.

clinical data - Trimm-2 study

TRIMM-2 (MMY1002; clinicaltrials.gov identifier: NCT04108195) is an ongoing, phase 1b, 2-part, multicohort, open-label study evaluating safety and efficacy of DARZALEX FASPRO regimens in combination with bispecific T-cell redirection antibodies in patients with RRMM.^5,15,16

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, and prior bispecific antibodies (BsAbs) and CAR-T were allowed.¹⁵
• Key primary endpoint: safety.^5,15,16

D'Souza et al (2024)⁵ presented the incidence of injection site reactions in the TECVAYLI + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 38.3 months (range, 1.2-39.6).

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 10 patients were administered the TECVAYLI + DARZALEX FASPRO + pomalidomide combination.
• 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.

Safety

• At a median follow-up of 38.3 months (range, 1.2-39.6), injection site erythema was reported in 30% of patients (n=3). No grade 3/4 injection site erythema was reported.

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 10 January 2025.