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(teclistamab-cqyv)

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TECVAYLI® (teclistamab-cqyv)

Medical Information

TECVAYLI - MajesTEC-4 (MMY3003)/EMN30 Study

Last Updated: 07/31/2025

Summary

  • Johnson & Johnson does not recommend any practices, procedures, or usage that deviate from the product labeling or are not approved by regulatory agencies.
  • MajesTEC-4 (EMN30; MMY3003) is an open-label, randomized, multicenter, phase 3 study assessing the efficacy and safety of TECVAYLI in combination with lenalidomide (Tec-Len) and TECVAYLI alone vs lenalidomide alone as maintenance therapy after autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (NDMM).1-3 
    • Zamagni et al (2024)3 presented the preliminary efficacy and safety results from the safety run-in (SRI) of Cohort 1 (Tec-Len; TECVAYLI weekly [QW] to every 4 weeks [Q4W]) at a median follow-up of 21.1 months (range, 14.8-23.8), Cohort 2 (Tec-Len; TECVAYLI Q4W) at a median follow-up of 9.2 months (range, 1.2-12.2), and Cohort 3 (TECVAYLI [Q4W]) at a median follow-up of 9.2 months (range, 3.7- 11.5).

CLINICAL DATA - MAJESTEC-4 STUDY

MajesTEC-4 (EMN30; MMY3003; clinicaltrials.gov identifier NCT05243797) is an open-label, randomized, multicenter, phase 3 study evaluating the efficacy and safety of Tec-Len and TECVAYLI alone vs lenalidomide alone as maintenance therapy in patients with NDMM.1,3

Study Design/Methods

  • The study design is presented in the Figure: MajesTEC-4/EMN30 Study Design.
  • An SRI period consisting of 3 cohorts was used to establish safety prior to enrolling the randomized phase of the study.3
  • Maintenance regimen (2-year fixed duration): patients who achieved complete response (CR) on Tec-Len after 1-year discontinued TECVAYLI and continued lenalidomide for an additional year.

MajesTEC-4/EMN30 Study Design1-3

Abbreviations: ADA, anti-drug antibody; AE, adverse event; ASCT, autologous hematopoietic stem cell transplantation; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; CR, complete response; ECOG PS, Eastern Cooperative Oncology Group performance status; EMN, Stichting European Myeloma Network; HRQoL, health-related quality of life; IMWG, International Myeloma Working Group; Len, lenalidomide; MRD, minimal residual disease; NDMM, newly diagnosed multiple myeloma; NGF, next-generation flow cytometry; NK, natural killer; OS, overall survival; PI, proteasome inhibitor; PFS, progression-free survival; PK, pharmacokinetics; PR, partial response; PRO, patient-reported outcome; Q4W, every 4 weeks; QW, weekly; SRI, safety run-in; SUD, step-up dosing; Tec, teclistamab; Tec-Len, teclistamab + lenalidomide; VGPR, very good partial response.
aPI and/or immunomodulatory drug ± anti-CD38 antibody.
bSingle or tandem ASCT permitted.
cPatients received step-up doses of 0.06 and 0.3 mg/kg.
dReceived on days 8, 15, and 22.
eStarted at 10 mg/day during cycles 2-4 in a 28-day cycle, increasing to 15 mg/day in cycles 5-26 if tolerated.
fReceived on days 8 and 15.

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

Results

Treatment Disposition


MajesTEC-4/EMN30 Study (SRI Cohorts): Demographics and Disease Characteristics3
Characteristic
Cohort 1
Tec-Len (QW to Q4W)
(N=32)
Cohort 2
Tec-Len (Q4W)
(N=32)
Cohort 3
Tec (Q4W)
(N=30)
Median age, years (range)
58.5 (31-73)
58.0 (38-73)
58.5 (34-72)
   ≥65, n (%)
12 (37.5)
5 (15.6)
9 (30.0)
Male, n (%)
21 (65.6)
21 (65.6)
22 (73.3)
White race, n (%)
32 (100)
32 (100)
30 (100)
ISS disease stage at diagnosis, n (%)
   I
18 (56.3)
8 (25.0)
9 (32.1)a
   II
7 (21.9)
9 (28.1)
11 (39.3)a
   III
7 (21.9)
15 (46.9)
8 (28.6)a
High cytogenetic risk at diagnosisb, n (%)
7 (28.0)c
5 (17.2)d
6 (24.0)c
ECOG-PS
0-1
0-1
0-1
Induction regimen for MM, n (%)
   PIe + immunomodulatory drugf
28 (87.5)
28 (87.5)
30 (100)
   PIe + immunomodulatory drugf +
   anti-CD38g
11 (34.4)
19 (59.4)
20 (66.7)
Prior consolidation, n (%)
6 (18.8)
12 (37.5)
10 (33.3)
Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; EMN, Stichting European Myeloma Network; ISS, International Staging System; Len, lenalidomide; MM, multiple myeloma; PI, proteasome inhibitor; Q4W, every 4 weeks; QW, weekly; SRI, safety run-in; Tec, TECVAYLI; Tec-Len, TECVAYLI + lenalidomide.
aEvaluated in 28 patients.
bPresence of ≥1 of the following abnormalities: del(17p), t(4;14), or t(14;16).
cEvaluated in 25 patients.
dEvaluated in 29 patients.
eOut of 94 patients in all 3 SRI cohorts, 93 patients (98.9%) received bortezomib and 3 patients (3.2%) received carfilzomib.
fOut of 94 patients in all 3 SRI cohorts, 53 patients (56.4%) received len, 39 patients (41.5%) received thalidomide, and 1 patient (1.1%) received pomalidomide.
gOut of 94 patients in all 3 SRI cohorts, 49 patients (52.1%) received daratumumab and 1 patient (1.1%) received isatuximab as part of a triplet regimen; 1 patient (1.1%) received daratumumab with len as part of a doublet regimen.

MajesTEC-4/EMN30 Study (SRI Cohorts): Treatment Disposition and Exposure3
Parameter, n
Cohort 1
Tec-Len (QW to Q4W)
(N=32)
Cohort 2
Tec-Len (Q4W)
(N=32)
Cohort 3
Tec (Q4W)
(N=30)
Treatment discontinuation
7
1
4
   AEs
3
1
1
   Patient withdrawal
2
-
1
   Physician decision
1
-
-
   Progressive disease
1
-
1
   Othera
-
-
1
Ongoing treatment
25
31
26
Abbreviations: AE, adverse event; EMN, Stichting European Myeloma Network; Q4W, every 4 weeks; QW, weekly; SRI, safety run-in; Tec, TECVAYLI; Tec-Len, TECVAYLI + lenalidomide.
Note: Median follow-up time: Cohort 1, 21.1 months (range, 14.8-23.8); Cohort 2, 9.2 months (range, 1.2 [censored observation]-12.2), Cohort 3, 9.2 months (range, 3.7-11.5). Clinical data cutoff date: September 9, 2024.
aPatient decision.

Efficacy


MajesTEC-4/EMN30 Study (SRI Cohorts): Response Rates After ASCT and During Maintenance3
Response, %
Cohort 1
Tec-Len (QW to Q4W)
(N=32)
Cohort 2
Tec-Len (Q4W)
(N=32)
Cohort 3
Tec (Q4W)
(N=30)
Response
after ASCTa
Best response
on maintenance
Response
after ASCTa
Best response
on maintenance
Response
after ASCTa
Best response
on maintenance
sCR
18.8
90.6
12.5
65.6
3.3
70.0
CR
18.8
9.4
12.5
25.0
30.0
23.3
VGPR
40.6
-
56.3
9.4
43.3
6.7
PR
21.9
-
18.8
-
23.3
-
≥CR
37.6
100.0
25.0
90.6
33.3
93.3
Abbreviations: ASCT, autologous stem cell transplantation; CR, complete response; EMN, Stichting European Myeloma Network; PR, partial response; Q4W, every 4 weeks; QW, weekly; sCR, stringent complete response; SRI, safety run-in; Tec, TECVAYLI; Tec-Len, TECVAYLI + lenalidomide; VGPR, very good partial response.
Note: Median follow-up: Cohort 1, 21.1 months (range, 14.8-23.8); Cohort 2, 9.2 months (range, 1.2 [censored observation]-12.2), Cohort 3, 9.2 months (range, 3.7-11.5). Clinical data cutoff date: September 9, 2024.
aAfter ASCT ± consolidation.

MajesTEC-4/EMN30 Study (SRI Cohorts): MRD Negativity (10-5) in Evaluable Patients After ASCT and During Maintenance3
Cohort 1
Tec-Len (QW to Q4W)
(N=32)
Cohort 2
Tec-Len (Q4W)
(N=32)
Cohort 3
Tec (Q4W)
(N=30)
After ASCTb
(n=27)
At 12 months
(n=28)
After ASCTb
(n=30)
At 6 months
(n=26)
After ASCTb
(n=30)
At 6 months
(n=22)
MRD-negativity ratea, %
63.0
100.0
83.3
100.0
73.3
100.0
Abbreviations: ASCT, autologous stem cell transplantation; EMN, Stichting European Myeloma Network; MRD, minimal residual disease; Q4W, every 4 weeks; QW, weekly; SRI, safety run-in; Tec, TECVAYLI; Tec-Len, TECVAYLI + lenalidomide.
Note: Median follow-up: Cohort 1, 21.1 months (range, 14.8-23.8); Cohort 2, 9.2 months (range, 1.2 [censored observation]-12.2), Cohort 3, 9.2 months (range, 3.7-11.5). Clinical data cutoff date: September 9, 2024.  aMRD-negativity rate was defined as the proportion of patients who achieved MRD negativity (10-5) regardless of response. The denominator for percentages is the number of evaluable patients. Among 87 evaluable patients, 23 patients were MRD positive at screening (Cohort 1, n=10; Cohort 2, n=5; Cohort 3, n=8). All patients who were MRD positive at study entry and had an assessment during treatment were MRD negative during treatment. One patient in Cohort 1 was MRD positive at 18 months.
bAfter ASCT ± consolidation.

Safety

  • Treatment-emergent adverse events (TEAEs) of any grade were reported in 100% of patients in all Cohorts. Grade 3/4 TEAEs were reported in 100% of patients (n=32) in Cohort 1, 84.4% of patients (n=27) in Cohort 2, and in 56.7% of patients (n=17) in Cohort 3. Additional details are provided in Tables: MajesTEC-4/EMN30 Study (SRI Cohorts): Hematologic AEs and MajesTEC-4/EMN30 Study (SRI Cohorts): Nonhematologic AEs.
  • Median relative dose intensity ranged from 95.5% to 99.7% for TECAVYLI and 58.4% to 61.5% for lenalidomide.
  • Overall treatment discontinuation rate was 5.3% due to TEAEs.
  • Cumulative incidence of grade 3/4 neutropenia at 6 months were 81.3% for Cohort 1, 56.3% for Cohort 2, and 40.0% for Cohort 3, respectively.
  • No immune effector cell-associated neurotoxicity syndrome (ICANS) was reported.
Cytokine Release Syndrome
  • Cytokine release syndrome (CRS) was reported in 50.0% of patients (n=16) in Cohort 1, 40.6% of patients (n=13) in Cohort 2, and in 43.3% of patients (n=12) in Cohort 3. All events were grade 1/2. The incidence of CRS was 37.2% after SUD 1, 8.5% after SUD 2 and 5.3% after treatment dose 1.
  • No discontinuations were reported due to CRS.
Infections and Hypogammaglobulinemia
  • Details on infections are provided in Table: MajesTEC-4/EMN30 Study (SRI Cohorts): Infections for details. One death due to coronavirus disease 2019 (COVID-19)-related TEAE was reported in SRI Cohort 2.
  • Hypogammaglobulinemia (including patients with ≥1 TEAE of hypogammaglobulinemia or post-baseline immunoglobulin G [IgG] <400 mg/dL) was reported in 96.9% of patients (n=31) in Cohort 1, 78.1% of patients (n=25) in Cohort 2, and 93.3% of patients (n=28) in Cohort 3. All patients received ≥1 dose of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIg).
  • Prophylactic 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.

MajesTEC-4/EMN30 Study (SRI Cohorts): Hematologic AEs3
Hematologic AEsa, n (%)
Cohort 1
Tec-Len (QW to Q4W)
(N=32)
Cohort 2
Tec-Len (Q4W)
(N=32)
Cohort 3
Tec (Q4W)
(N=30)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Neutropenia
30 (93.8)
30 (93.8)
21 (65.6)
20 (62.5)
17 (56.7)
14 (46.7)
Leukopenia
9 (28.1)
3 (9.4)
1 (3.1)
0
1 (3.3)
1 (3.3)
Lymphopenia
2 (6.3)
1 (3.1)
4 (12.5)
4 (12.5)
4 (13.3)
4 (13.3)
Febrile neutropenia
3 (9.4)
3 (9.4)
3 (9.4)
3 (9.4)
0
0
Anemia
3 (9.4)
0
1 (3.1)
1 (3.1)
1 (3.3)
0
Thrombocytopenia
6 (18.8)
2 (6.2)
0
0
2 (6.7)
0
Eosinophilia
1 (3.1)
1 (3.1)
1 (3.1)
1 (3.1)
0
0
Abbreviations: AE, adverse event; EMN, Stichting European Myeloma Network; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; Q4W, every 4 weeks; QW, weekly; SRI, safety run-in; Tec, TECVAYLI; Tec-Len, TECVAYLI + lenalidomide.
Note: Clinical data cutoff date: September 9, 2024.
aAEs (graded according to the NCI-CTCAE version 5.0) occurring in >25% of patients with any grade AEs or >1 patient with grade 3/4 AEs in any arm.

MajesTEC-4/EMN30 Study (SRI Cohorts): Nonhematologic AEs3
Nonhematologic AEsa,b, n (%)
Cohort 1
Tec-Len (QW to Q4W)
(N=32)
Cohort 2
Tec-Len (Q4W)
(N=32)
Cohort 3
Tec (Q4W)
(N=30)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
CRS
16 (50.0)
0
13 (40.6)
0
13 (43.3)
0
URTI
20 (62.5)
1 (3.1)
13 (40.6)
0
8 (26.7)
0
Cough
15 (46.9)
0
6 (18.8)
0
8 (26.7)
0
COVID-19
12 (37.5)
1 (3.1)
5 (15.6)
0
9 (30.0)
1 (3.3)
Fatigue
10 (31.3)
1 (3.1)
8 (25.0)
1 (3.1)
5 (16.7)
0
Diarrhea
13 (40.6)
3 (9.4)
9 (28.1)
1 (3.1)
6 (20.0)
0
Pneumonia
9 (28.1)
4 (12.5)
3 (9.4)
0
2 (6.7)
1 (1.3)
Injection site erythema
7 (21.9)
0
12 (37.5)
0
8 (26.7)
0
Abbreviations: AE, adverse event; CRS, cytokine release syndrome; COVID-19, coronavirus disease 2019; EMN, Stichting European Myeloma Network; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; Q4W, every 4 weeks; QW, weekly; SRI, safety run-in; TEAE, treatment-emergent adverse event; Tec, TECVAYLI; Tec-Len, TECVAYLI + lenalidomide; URTI, upper respiratory tract infection.
Note: Clinical data cutoff date: September 9, 2024.
aAEs (graded according to the NCI-CTCAE version 5.0) occurring in >25% of patients with any grade AEs or >1 patient with grade 3/4 AEs in any arm.
bHypogammaglobulinemia based on TEAE reporting also met the ≥25% threshold and is reported separately.

MajesTEC-4/EMN30 Study (SRI Cohorts): Infections3
Infectionsa,b, n (%)
Cohort 1
Tec-Len (QW to Q4W)
(N=32)
Cohort 2
Tec-Len (Q4W)
(N=32)
Cohort 3
Tec (Q4W)
(N=30)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any infection
30 (93.8)
12 (37.5)
25 (78.1)
9 (28.1)
23 (76.7)
6 (20.0)
Most common infectionsc
URTI
20 (62.5)
1 (3.1)
13 (40.6)
0
8 (26.7)
0
COVID-19
12 (37.5)
1 (3.1)
5 (15.6)
0
9 (30.0)
1 (3.3)
Pneumonia
9 (28.1)
4 (12.5)
3 (9.4)
0
2 (6.7)
1 (3.3)
Nasopharyngitis
6 (18.8)
0
0
0
3 (10.0)
0
Abbreviations: COVID-19, coronavirus disease 2019; EMN, Stichting European Myeloma Network; IgG, immunoglobulin; IVIG, intravenous immunoglobulin; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; PCP, Pneumocystis carinii pneumonia; PJP, Pneumocystis jirovecii pneumonia; Q4W, every 4 weeks; QW, weekly; SRI, safety run-in; Tec, TECVAYLI; Tec-Len, TECVAYLI + lenalidomide; URTI, upper respiratory tract infection.
Note: Clinical data cutoff date: September 9, 2024.  
aAdverse events (graded according to the NCI-CTCAE version 5.0).
bProphylactic IVIG replacement advised to maintain serum IgG levels of ≥400 mg/dL. Prophylaxis for PCP/PJP and herpes zoster reactivation and routine antibiotic and antiviral prophylaxis were recommended.
cOccurring in >10% of patients with any grade AEs in any arm.

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 17 December 2024.

 

References

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1 European Myeloma Network. Phase 3 study of teclistamab in combination with lenalidomide and teclistamab alone versus lenalidomide alone in participants with newly diagnosed multiple myeloma as maintenance therapy following autologous stem cell transplantation (MajesTEC-4). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [Cited 2024 December 17]. Available from: https://clinicaltrials.gov/ct2/show/NCT05243797 NLM Identifier: NCT05243797.  
2 Zamagni E, Boccadoro M, Spencer A, et al. MajesTEC-4 (EMN30): a phase 3 trial of teclistamab + lenalidomide and teclistamab alone versus lenalidomide alone as maintenance therapy following autologous stem cell transplantation in patients with newly diagnosed multiple myeloma. presented at: 64th American Society of Hematology (ASH) Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA/Virtual meeting.  
3 Zamagni E, Silzle T, Špička I, et al. Phase 3 study of teclistamab with lenalidomide, teclistamab alone, and lenalidomide alone as maintenance therapy in newly diagnosed multiple myeloma post-autologous stem cell transplant: Safety run-in results from the EMN30/MajesTEC-4 trial. Oral Presentation presented at: The 66th American Society of Hematology (ASH) Annual Meeting; December 7-10, 2024; San Diego, CA.