TECVAYLI - MajesTEC-9 Study

SUMMARY

• Johnson & Johnson does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• MajesTEC-9 is an ongoing, phase 3, randomized, open-label, multicenter study comparing TECVAYLI with investigator’s choice of pomalidomide, bortezomib and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma (RRMM) who previously received 1-3 prior lines of therapy (LOTs) including an anti-CD38 monoclonal antibody (mAb) and lenalidomide.¹
  • Touzeau et al (2026)^1,2 published initial efficacy and safety results of the MajesTEC-9 study at a median follow-up of 17.3 months.
    • At a median follow‑up of 17.3 months, the risk of progression or death was reduced with TECVAYLI vs PVd/Kd (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.23-0.38; P<0.001). The estimated 18-month progression-free survival (PFS) was 69.8% vs 26.9% for TECVAYLI vs PVd/Kd arms, respectively.
    • Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 84.9% vs 76.3% in the TECVAYLI vs PVd/Kd arms, respectively.

CLINICAL DATA - MajeSTEC-9 Study

MajesTEC-9 (NCT05572515) is an ongoing, phase 3, randomized, open-label, multicenter study comparing TECVAYLI with investigator’s choice of PVd or Kd in patients with RRMM who previously received 1-3 prior LOTs including an anti-CD38 mAb and lenalidomide.¹

Study Design/Methods

• The study design is presented in the Figure: MajesTEC-9 Study Design.¹

Touzeau et al (2026)^1,2 published initial efficacy and safety results of the MajesTEC-9 study at a median follow-up of 17.3 months.

Results

Treatment Disposition and Baseline Characteristics

• Of the 593 patients randomized (TECVAYLI, n=296; PVd/Kd, n=297), 574 patients received study treatment (TECVAYLI, n=291 [98.3%]; PVd/Kd, n=283 [95.3%]).
  • Of the 283 patients who received PVd/Kd, 69.6% (n=197) received Kd and 30.4% (n=86) received PVd.
• The baseline demographics and disease characteristics were generally balanced between the TECVAYLI (n=296) and PVd/Kd (n=297) treatment arms.
  • The median age was 70 years (range, 34-85) in the TECVAYLI arm and 70 years (range, 36-86) in the PVd/Kd arm; 28.4% of patients (n=84/296) in the TECVAYLI arm and 30% of patients (n=89/297) in the PVd/Kd arm were aged ≥75 years.
  • Male patients comprised 50.7% of patients (n=150/296) in the TECVAYLI arm and 51.5% of patients (n=153/297) in the PVd/Kd arm.
  • In the TECVAYLI arm, 14.2% of patients (n=42/296) were classified as International Staging System (ISS) stage III, compared with 15.2% of patients (n=45/297) in the PVd/Kd arm.
  • Revised ISS (RISS) stage III disease was observed in 9.3% of patients (n=24/258) in the TECVAYLI arm and 10.8% of patients (n=28/259) in the PVd/Kd arm.
  • Highrisk cytogenetics (≥1 of del[17p], t[4;14], or t[14;16]) were identified in 35.7% of patients (n=105/294) receiving TECVAYLI and 35.1% of patients (n=104/296) receiving PVd/Kd.
  • The presence of ≥1 softtissue plasmacytoma was reported in 18.2% of patients (n=54/296) in the TECVAYLI arm and 21.9% of patients (n=65/297) in the PVd/Kd arm.
  • The median number of prior LOTs was 2 (range, 1-3) in both treatment arms; 78.4% of patients (n=232/296) in the TECVAYLI arm and 78.5% of patients (n=233/297) in the PVd/Kd arm had received 2-3 prior LOTs.
  • All patients (100%) in both treatment arms had prior exposure to an immunomodulatory drug and an antiCD38 antibody.
  • The majority of patients were refractory to any immunomodulatory drug, including 82.8% of patients (n=245/296) in the TECVAYLI arm and 84.5% of patients (n=251/297) in the PVd/Kd arm.
    • Lenalidomiderefractory disease was observed in 79.1% of patients (n=234/296) treated with TECVAYLI and 80.8% of patients (n=240/297) treated with PVd/Kd.
  • Tripleclass refractory (refractory to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 mAb) disease was reported in 34.5% of patients (n=102/296) in the TECVAYLI arm and 33% of patients (n=98/297) in the PVd/Kd arm.
• Among patients randomized to TECVAYLI (n=296), the median time from diagnosis of multiple myeloma to randomization was 3.8 years (range, 0.3-21), compared with 3.5 years (range, 0.2-22.1) among patients randomized to PVd/Kd (n=297).

Efficacy

• The median duration of study treatment was 13.1 months for patients treated with TECVAYLI (n=296) and 7 months for patients treated with PVd/Kd (n=297).
• At a median follow-up of 17.3 months, TECVAYLI reduced the risk of disease progression or death compared with PVd/Kd (HR, 0.29; 95% CI, 0.23-0.38; P<0.001). See Table: 18-Months Estimates: DOR, PFS, OS.
• TECVAYLI significantly lowered the risk of death compared to PVd/Kd (HR, 0.60; 95% CI, 0.43-0.83; P=0.002).
• Overall response rate (ORR; defined as a partial response or better [≥PR]) in TECVAYLI vs PVd/Kd arm was 84.5% vs 54.2% (risk ratio, 1.56 [95% CI, 1.39-1.75]).
  • Stringent complete response (sCR): 53.7% vs 9.4%
  • Complete response (CR): 12.2% vs 7.4%
  • Very good partial response (VGPR): 14.2% vs 19.5%
  • Partial response (PR): 4.4% vs 17.8%
  • Minimal response: 0% vs 6.1%
  • Stable disease: 8.8% vs 27.3%
  • Progressive disease: 4.4% vs 8.1%
  • Not evaluable: 2.4% vs 4.4%
• Complete response or better (≥CR) was achieved by 65.9% of patients treated with TECVAYLI vs 16.8% of patients treated with PVd/Kd (risk ratio, 3.95 [95% CI, 3.03-5.14, P<0.001]) with similar effects observed across subgroups.
• Very good partial response or better (≥VGPR) was achieved by 80.1% of patients treated with TECVAYLI compared with 36.4% of patients treated with PVd/Kd (risk ratio, 2.20 [95% CI, 1.88-2.59]).
• Minimal residual disease (MRD) negativity at the 10^-5 threshold was achieved in 42.2% of patients (125/296) treated with TECVAYLI, compared with 7.7% of patients (23/297) treated with PVd/Kd. This corresponded to an odds ratio of 8.89 (95% CI, 5.45-14.52) in favor of TECVAYLI.
  • In the intentiontotreat population, 38.5% of patients (n=296) treated with TECVAYLI achieved MRDnegative ≥CR, compared with 6.7% of patients (n=297) treated with PVd/Kd (risk ratio, 5.76 [95% CI, 3.69-9.01]; odds ratio, 8.56 [95% CI, 5.14-14.26]).
  • In the next‑generation flow cytometryevaluable set, 86.4% of patients (n=132) treated with TECVAYLI achieved MRDnegative ≥CR, compared with 45.5% of patients (n=44) treated with PVd/Kd (risk ratio, 1.94 [95% CI, 1.37-2.76]; odds ratio, 6.80 [95% CI, 3.05-15.16]).

Safety

• Anygrade TEAEs were reported in 99.7% of patients (290/291) in the TECVAYLI arm and 97.9% (277/283) in the PVd/Kd arm.
  • Grade 3/4 TEAEs were reported in 84.9% of patients (247/291) in the TECVAYLI arm and 76.3% (216/283) in the PVd/Kd arm.
  • See Table: Summary of Most Common Treatment-Emergent Adverse Events (Safety Population) for additional details.
• Serious adverse events (SAEs) were reported in 56.7% of TECVAYLI‑treated patients and 45.6% of PVd/Kd‑treated patients.

Treatment Dose Modifications

• As of the clinical cutoff date of October 13, 2025, 34.7% of patients treated with TECVAYLI (n=296) and 76% of patients treated with PVd/Kd (n=297) had discontinued study treatment, primarily due to progressive disease (TECVAYLI, 20.6%; 54.1%, PVd/Kd).
• Cycle delays were reported in 66.3% of patients (193/291) treated with TECVAYLI vs 69.8% of patients (60/86) receiving PVd and 39.1% of patients (77/197) receiving Kd.
  • Dose delays: 19.9% (58/291) with TECVAYLI, 11.6% (10/86) for bortezomib (PVd), 9.3% (8/86) for dexamethasone (PVd), 6.1% (12/197) for dexamethasone (Kd), and 5.6% (11/197) for carfilzomib (Kd).
  • Dose skipped: 44.3% (129/291) with TECVAYLI, 57% (49/86) for pomalidomide (PVd), 62.8% (54/86) for bortezomib (PVd), 54.7% (47/86) for dexamethasone (PVd), 58.9% (116/197) for dexamethasone (Kd), and 55.3% (109/197) for carfilzomib (Kd).
  • Dose reduced: 5.8% (17/291) with TECVAYLI, 39.5% (34/86) for pomalidomide (PVd), 34.9% (30/86) for bortezomib (PVd), 52.3% (45/86) for dexamethasone (PVd), 47.7% (94/197) for dexamethasone (Kd), and 28.9% (57/197) for carfilzomib (Kd).
  • Schedule modification to monthly dosing occurred in 33.7% of patients (n=98/291) treated with TECVAYLI prior to cycle 7 due to confirmed very good partial response or better, with 71% of these patients (n=70/98) switching by cycle 5.

Hematologic Events

• Neutropenia was reported in 62.5% (182/291) of patients treated with TECVAYLI and 28.6% (81/283) of patients treated with PVd/Kd; grade 3/4 neutropenia was reported in 54.3% (158/291) vs 22.3% (63/283), respectively.
• Lymphopenia was reported in 24.4% (71/291) of patients treated with TECVAYLI and 17.3% (49/283) of patients treated with PVd/Kd; grade 3/4 lymphopenia was reported in 20.3% (59/291) vs 11.3% (32/283), respectively.
• Thrombocytopenia was reported in 27.5% (80/291) of patients treated with TECVAYLI and 38.9% (110/283) of patients treated with PVd/Kd; grade 3/4 thrombocytopenia was reported in 10.7% (31/291) vs 21.2% (60/283), respectively.
• Anemia was reported in 37.8% (110/291) of patients treated with TECVAYLI and 42% (119/283) of patients treated with PVd/Kd; grade 3/4 anemia was reported in 17.9% (52/291) vs 16.3% (46/283), respectively.
• Any‑onset cytopenias of grade ≥3 occurred most frequently during the first 6 months of treatment and decreased thereafter.

Deaths

• Deaths during the study were reported in 19.2% of patients (56/291) treated with TECVAYLI and 29.3% of patients (83/283) treated with PVd/Kd.
• Disease progression was the most common primary cause of death, reported in 8.6% of patients (25/291) in the TECVAYLI arm and 18.7% of patients (53/283) in the PVd/Kd arm.
• Investigator-attributed treatment-related events resulted in deaths in 4.1% of patients (n=12) in the TECVAYLI group and 1.8% of patients (n=5) in the PVd/Kd group.
• Deaths due to TEAEs were reported in 6.5% of patients (19/291) receiving TECVAYLI and 3.5% of patients (10/283) receiving PVd/Kd.
• Deaths occurring within 30 days of the last study treatment dose were reported in 6.2% of patients (18/291) treated with TECVAYLI and 8.1% of patients (23/283) treated with PVd/Kd.
• Deaths occurring within 60 days of the first study treatment dose were reported in 3.4% of patients (10/291) in the TECVAYLI arm and 5.7% of patients (16/283) in the PVd/Kd arm.
• In the TECVAYLI arm, death due to adverse events by preferred term included:
  • COVID‑19 pneumonia (1.0% [3/291]), pneumonia (1.0% [3/291]), pulmonary sepsis (0.7% [2/291]), urosepsis (0.7% [2/291]), COVID‑19 (0.3% [1/291]), enteroviral encephalitis (0.3% [1/291]), aspiration pneumonia (0.3% [1/291]), bacterial pneumonia (0.3% [1/291]), Klebsiella pneumonia (0.3% [1/291]), West Nile viral infection (0.3% [1/291]), cardio‑respiratory arrest (0.3% [1/291]), acute kidney injury (0.3% [1/291]), pulmonary alveolar hemorrhage (0.3% [1/291]), and death (0.3% [1/291]).

Cytokine Release Syndrome

• Cytokine release syndrome (CRS) events were reported in 66% of patients (192/291) treated with TECVAYLI.
  • Most CRS events were grade 1 (142/291, 48.8%) and grade 2 (48/291, 16.5%).
  • Grade 3 CRS events were reported in 0.7% of patients (2/291; one with concurrent pneumonia); grade ≥4 CRS events were not reported.
• CRS occurred primarily during stepup dosing, including stepup dose 1 (35.1%), stepup dose 2 (35.4%), and repeat step-up dosing cycle 1 (65.6%).
• All CRS events resolved (100%). The median duration of CRS was 2 days (range, 1-21), and no CRS events led to TECVAYLI discontinuation or death.
• Supportive measures were used in 62.5% of patients (182/291), most commonly tocilizumab (35.1% [102/291]).

Immune Effector Cell-Associated Neurotoxicity Syndrome

• Immune effector cell-associated neurotoxicity syndrome (ICANS) events were reported in 4.1% of patients (12/291) treated with TECVAYLI.
• Most ICANS events were grade 1 (7/291, 2.4%) and grade 2 (4/291, 1.4%).
• Grade 3 ICANS event was reported in 1 patient (1/291, 0.3%) which did not resolve and led to TECVAYLI discontinuation.
  • ICANS events were resolved (11/12, 91.7%).
  • No grade 4/5 ICANS events were reported.
• ICANS leading to TECVAYLI discontinuation occurred in 0.3% of patients (1/291).
• The median duration of ICANS was 2 days (range, 1-3) with most occurring during repeat step-up dosing cycle 1 (12/291, 4.1%).
• Concurrent CRS was reported in 66.7% of ICANS cases (8/12).

Infections

• Any-grade infections were reported in 82.8% of patients (241/291) in the TECVAYLI arm and 68.2% of patients (193/283) in the PVd/Kd arm.
• Grade 3/4 infections were reported in 41.6% of patients (121/291) receiving TECVAYLI and 29% of patients (82/283) receiving PVd/Kd.
• Any-grade treatment‑emergent opportunistic infections were reported in 14.4% of patients (42/291) in the TECVAYLI arm and 6.4% (18/283) in the PVd/Kd arm.
  • Grade 3/4 opportunistic infections were reported in 5.8% of patients (17/291) in the TECVAYLI arm and 1.1% (3/283) in the PVd/Kd arm.
• Pneumonia was the most frequent grade 3/4 treatment emergent infection in 14.4% of patients (42/291) treated with TECVAYLI and 10.6% of patients (30/283) treated with PVd/Kd.
• Grade ≥3 infections occurred most frequently during the first 6 months of treatment in both treatment arms and decreased thereafter.
• Fatal infections were reported in 5.5% of patients (16/291) treated with TECVAYLI and 2.8% of patients (8/283) treated with PVd/Kd, with most fatal infections occurring within the first 6 months of treatment initiation.
• Among patients with fatal infections, 5 of 16 patients treated with TECVAYLI and 6 of 8 patients treated with PVd/Kd did not receive immunoglobulin replacement, and 8 patients and 2 patients, respectively, had a last serum immunoglobulin G (IgG) level <400 mg/dL.
• Hypogammaglobulinemia was reported in 69.1% of patients treated with TECVAYLI and 50.2% of patients treated with PVd/Kd.
• Immunoglobulin replacement therapy was administered to 94.5% of patients (275/291) treated with TECVAYLI and 53.4% of patients (151/283) treated with PVd/Kd during the study.
• Treatment-emergent opportunistic infections of any grade by pathogen type in the TECVAYLI vs PVd/Kd arms included viral infections in 10.7% of patients (31/291) vs 4.2% of patients (12/283), bacterial infections in 0.7% of patients (2/291) vs 0.4% of patients (1/283), and fungal infections in 4.5% of patients (13/291) vs 1.8% of patients (5/283), respectively.

Second Primary Malignancies

• Second primary malignancies were reported in 6.9% of patients (20/291) treated with TECVAYLI and 3.9% of patients (11/283) treated with PVd/Kd, with the majority of cases being cutaneous or noninvasive in both arms (4.1% vs 2.8%, respectively).

Immunogenicity

• Anti-TECVAYLI antibodies were low, occurring in 1% of patients (3/287).

Patient-Reported Outcomes and Subsequent Therapy

• Time to symptom worsening based on the MySIm‑Q total symptom score was prolonged with TECVAYLI compared with PVd/Kd, with a hazard ratio of 0.50 (95% CI, 0.36-0.71; P<0.0001).
• The estimated 18‑month event‑free rate for symptom worsening was 73.5% (95% CI, 66.5-79.2) with TECVAYLI and 55.1% (95% CI, 45.2-64) with PVd/Kd.
• Subsequent antimyeloma therapy was received by 18.2% of patients (54/296) in the TECVAYLI arm and 58.6% of patients (174/297) in the PVd/Kd arm.
• Among patients who initiated subsequent therapy, 68.4% of patients received a bispecific antibody or CAR‑T therapy, compared with 9.3% of patients following TECVAYLI.

LITERATURE SEARCH

A literature search of Ovid MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 01 June 2026.