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TECVAYLI® (teclistamab-cqyv)

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RedirecTT-1 Study - TALVEY AND TECVAYLI Cohort

Last Updated: 12/19/2025

SUMMARY

  • Janssen does not recommend the use of TALVEY or TECVAYLI® (teclistamab-cqyv) in a manner that is inconsistent with the approved labeling.
  • RedirecTT-1 is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of the TALVEY and TECVAYLI combination in patients with relapsed or refractory multiple myeloma (RRMM), including those with extramedullary disease (EMD).1-8
    • Phase 2 study:
      • Usmani et al (2025)6 presented efficacy and safety results from phase 2 of the RedirecTT-1 study in patients with RRMM and EMD at a median follow-up of 16.8 months. The overall response rate (ORR) was 79%, and the most common any-grade adverse events (AEs) were oral AEs (86.7%), infections (80%), and cytokine release syndrome (CRS; 77.8%) in the TALVEY + TECVAYLI cohort.
      • Kumar et al (2025)8,9 published efficacy and safety results from phase 2 of the RedirecTT-1 study in patients with RRMM and EMD at a median follow-up of 12.6 months (range, 0.5-19.5). The ORR was 79% in the TALVEY + TECVAYLI cohort. Grade 3/4 AEs were reported in 76% of patients (n=68).
    • Phase 1b study:
      • Mateos et al (2025)7 presented the efficacy and safety from phase 1b of the RedirecTT-1 study in RRMM patients with and without EMD.
        • All dose levels (dose levels 1-5; N=94): At a median follow-up of 38 months, the ORR was 78%. The most common any-grade AEs reported were infections (93.6%), CRS (80.9%), and oral AEs (78.7%).
        • Recommended phase 2 regimen (RP2R; dose level 5; n=44): At a median
          follow-up of 34.5 months, the ORR was 80%.
      • Cohen et al (2025)3,10 published early safety and efficacy results from the phase 1 dose-escalation segment of the RedirecTT-1 study in RRMM patients with and without EMD.
        • All dose levels (dose levels 1-5; N=94): At a median follow-up of 20.3 months (range, 0.5-37.1), the ORR was 78%. Any-grade AEs were reported in all patients, with grade 3/4 AEs reported in 96% of patients (n=90).
        • RP2R (dose level 5; n=44): At a median follow-up of 18.2 months (range, 0.7-27.0), the ORR was 80%.
      • Cohen et al (2023)2 presented the preliminary efficacy and safety results at all dose levels (N=93) at a median follow-up of 13.4 months, and the RP2R cohort (n=34) at a median follow-up of 8.1 months.

PRODUCT LABELING

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

RedirecTT-1 (NCT04586426) is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of the combination of TALVEY and TECVAYLI in patients with RRMM including those with EMD.1-8

EMD was defined as ≥1 soft-tissue plasmacytoma measuring ≥2 in its largest dimension, as confirmed by central Positron Emission Tomography (PET)-Computed Tomography (CT) scan review.5

Study Design/Methods

RedirecTT-1 (Phase 1): Study Design1,3,7,10,11

Abbreviations: DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; EMD, extramedullary disease; LOT, line of therapy; mAb, monoclonal antibody; MM, multiple myeloma; ORR, overall response rate; PD, pharmacodynamics; PFS, progression-free survival; PI, proteosome inhibitor; PK, pharmacokinetic; PR, partial response; Q2W, every other week; Q4W, once every 4 weeks; QW, weekly, RP2R, recommended phase 2 regimen; SUD, step-up dose; Tal, talquetamab; Tec, teclistamab.
aNonsecretory or oligosecretory EMD were permitted.
bTal and Tec were administered on the same day, 30 (±10) minutes apart, for all step-up and full treatment doses.
cSUD was administered 2-4 days apart and prior to full treatment doses. Hospitalization and pretreatment with dexamethasone, diphenhydramine, and acetaminophen were required before all SUD and first treatment dose.

RedirecTT-1 (Phase 2 Tal + Tec in EMD): Study Design5,6,11  

Abbreviations: BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor;  T-cell; CR, complete response; CT, Computed Tomography; DOR, duration of response; EMD, extramedullary disease; FDG, F-fluorodeoxyglucose; GPCRD5, G protein-coupled receptor class C group 5 member; IMWG, International Myeloma Working Group; mAb, monoclonal antibody; MM, multiple myeloma; ORR, overall response rate; OS, overall survival; PET, Positron Emission Tomography; PFS, progression-free survival; PI, proteosome inhibitor; PK, pharmacokinetic; Q2W, every other week; Q4W, once every 4 weeks; RRMM, relapsed/refractory multiple myeloma; SC, subcutaneous; sCR, stringent complete response; SUD, step-up dose; Tal, talquetamab; Tec, teclistamab; VGPR, very good partial response.

aPatients may have had paramedullary plasmacytomas in addition to true EMD; however, patients with paramedullary plasmacytomas alone, central nervous system involvement, or plasma-cell leukemia were excluded.
bWhole body MRI permitted with sponsor approval.
cPrior PI, immunomodulatory drug, and anti-CD38 mAb.
dTal and Tec were administered on the same day. Tec should be administered 30 (±10) minutes before Tal, for all step-up and full treatment doses.
eUntil disease progression.

fResponse and PFS were assessed by an independent review committee per IMWG criteria. EMD response assessed by central radiology review of whole-body FDG-PET-CT scans or diffusion-weighted whole body MRI results, and findings were interpreted with the use of a functional Deauville score (scores from 1 to 5, with higher scores indicating greater uptake of FDG at involved sites on PET) and Italian myeloma criteria for PET use (IMPETUS).

RedirecTT-1 (Phase 2: Tal + Tec in EMD): SUD Schedule6,8,9 

Abbreviations: Q2W, every other week; SC, subcutaneous; Tal, talquetamab; Tec, teclistamab.
aUntil disease progression

Usmani et al (2025)6 presented the efficacy and safety results from the RedirecTT-1 phase 2 study in patients with RRMM and EMD at a median follow-up of 16.8 months.

Study Design/Methods

  • As IMWG criteria do not provide PET-CT-specific response criteria, an FDG-PET 5-point scale per Deauville and IMPETUS criteria was incorporated for radiographic criteria for EMD response:
    • Complete response (CR) was defined as disappearance of all plasmacytomas or persistence of fibrotic disease with PET score 1-3.
    • Very good partial response (VGPR) and partial response (PR) were defined as ≥90% or ≥50% reduction in size, respectively, in all plasmacytomas, with a reduction in PET avidity compared to baseline.
  • In nonsecretory disease, response was evaluated by functional imaging, and IMWG criteria also had to be met for CR.
  • Prospective EMD response was assessed by central radiology using FDG PET-CT, Deauville scale, and IMPETUS criteria.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics


RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Baseline Characteristics5,6
Characteristic
TALVEY + TECVAYLI
(N=90)
Median age, years (range)
64.5 (42-84)
Male, n (%)
57 (63.3)
Race, n (%)
   White
64 (71.1)
   Black/African American
8 (8.9)
   Asian
13 (14.4)
   Not reported
5 (5.6)
True extramedullary plasmacytomas ≥1a, n (%)
90 (100)b
Number of extramedullary plasmacytomasa, median (range)
2 (1-7)
Number of extramedullary plasmacytomasa, median (range)
   1
38 (42.2)
   2-3
29 (32.2)
   ≥4
23 (25.6)
EMD tumor locationc, n (%)
Lymph node
42.2 (95)
   Organ
35.6 (63)
   Soft tissue
56.7 (78)
   Paramedullaryd
23.3 (32)
EMD tumor volumee, %
   <25 cm2
47.8
   25-50 cm2
23.3
   >50 cm2
28.9
High-risk cytogeneticsf
21.5
Measurable diseaseg, n (%)
   Nonsecretory
4 (4.4)
   Oligosecretory
31 (34.4)
ECOG PS, n (%)
   0
32 (35.6)
   1
50 (55.6)
   2
8 (8.9)
Median years since diagnosish, years (range)
4.7 (0.7-21.4)
Median prior lines of therapy, n (range)
4.0 (1-10)
Exposure status, n (%)
   Belantamab mafodotin
11 (12.2)
   Anti-BCMA CAR-T therapy
18 (20.0)
   BsAb therapyi
8 (8.9)
   Triple-class
90 (100)
   Penta-drug
51 (56.7)
Refractory status, n (%)
   PI
86 (95.6)
   Immunomodulatory drug
84 (93.3)
   Anti-CD38 mAb
85 (94.4)
   Triple-class
76 (84.4)
   Penta-drug
32 (35.6)
   To last line of therapy
75 (83.3)
Abbreviations: BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T-cell; CT, computed tomography; ECOG PS, Eastern Cooperative Oncology Group performance status; EMD, extramedullary disease; FcRH5, Fc receptor-homolog 5; FISH, fluorescence in situ hybridization; IMWG, International Myeloma Working Group; mAb, monoclonal antibody; PET, positron emission tomography; PI, proteasome inhibitor.
Clinical data cutoff date of March 18, 2025.
aEMD defined as ≥1 nonradiated bone-independent soft-tissue plasmacytoma ≥2 cm in greatest dimension, confirmed by PET-CT scans. A total of 6 patients had data on the number of EMD lesions based on investigator assessment only.
bParaskeletal lesions were also present in 19 patients.
cPatients could have ≥1 EMD location.
dParamedullary lesions were also present alongside true EMD in 23.3% of patients (n=21).
eVolume assessed for true EMD only.
fAssessed using FISH or karyotype testing in 65 patients. Defined as del(17p), t(4;14), or t(14;16) abnormality.
gPer IMWG criteria.
hEvaluated in 89 patients.
iAll patients received anti-FcRH5 BsAbs.

Efficacy


RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Efficacy Outcomes6
Parameter
TALVEY + TECVAYLI
(N=90)
ORRa,b, % (95% CI)
79 (69.0-87.0)
   sCR, %
44
   CR, %
9
   VGPR, %
17
   PR, %
9
≥CR, %
53
Median time to first response, months (range)
2.6 (1.0-5.8)
Median time to best response, months (range)
5.1 (1.0-16.6)
Median DORc, months (95% CI)
NR (11.5-NE)
   12-month DOR rate, % (95% CI)
62.1 (49.0-72.7)
Median PFSd, months (95% CI)
15.0 (10.3-NE)
   12-month PFS rate, % (95% CI)
57.5 (46.4-67.1)
Median OSe, months (95% CI)
NR (19.7-NE)
   12-month OS rate, % (95% CI)
73.8 (63.3-81.8)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; IMWG, International Myeloma Working Group; NE, not estimable; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cutoff date of July 18, 2025. Median follow-up 16.8 months.
aResponse was assessed by the investigator per IMWG criteria.
bDue to rounding, individual response rates may not sum to the ORR.
cAt time of data cutoff, 60.6% of patients (n=43) were censored for DOR.
dAt time of data cutoff, 50.0% of patients (n=45) were censored for PFS.
eAt time of data cutoff, 65.6% of patients (n=59) were censored for OS.

RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Efficacy Outcomes Per EMD Location6
Parameter
Organ EMDa
(n=32)
Nonorgan EMDb
(n=58)
ORRc,d, % (95% CI)
78 (60-91)
79 (67-89)
   sCR, %
47
43
   CR, %
9
9
   VGPR, %
16
17
   PR, %
6
10
≥CR, %
56
52
Median DOR, months
NR
15.4
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; EMD, extramedullary disease; IMWG, International Myeloma Working Group; NR, not reached; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cutoff date of July 18, 2025. Median follow-up 16.8 months.
aOrgan EMD locations include adrenal gland, kidney, liver (left lobe, right lobe), lung (left, left lower lobe), pancreas, pericardium, peritoneum, and pleura.
bNon-organ EMD locations include lymph node (axillary, cervical, iliac, inguinal, lymph, mediastinal, mesenteric, para-aortic, pelvic, peripancreatic, porta hepatis, retrocrural, retroperitoneal, and supraclavicular) and soft-tissue (abdominal, breast, chest wall, mediastinum, muscle, omentum, other, pelvis, retroperitoneum, and skin).
cResponse was assessed by the investigator per IMWG criteria.
dDue to rounding, individual response rates may not sum to the ORR.

RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Efficacy Outcomes Per Baseline EMD Tumor Volume6
Response
Total
(N=90)
<25 cm²
(n=43)
25-50 cm²
(n=21)
>50 cm²
(n=26)
ORRa,b, % (95% CI)
79 (69-87)
93 (81-99)
67 (43-85)
65 (44-83)
   sCR, %
44
51
43
35
   CR, %
9
7
14
8
   VGPR, %
17
21
10
15
   PR, %
9
14
-
8
≥CR, %
53
58
57
42
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; EMD, extramedullary disease; IMWG, International Myeloma Working Group; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cutoff date of July 18, 2025. Median follow-up 16.8 months.
aResponse was assessed by the investigator per IMWG criteria.
bDue to rounding, individual response rates may not sum to the ORR.

Safety

Infections and Hypogammaglobulinemia
  • Details on infections are presented in Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Infections (≥10% Overall).
  • Grade 3/4 infections were reported in 33.3% of patients (n=30); mostly limited to first six months and then declined.
  • The median duration of infection was 13.0 days.
  • A total of 6.7% of patients had opportunistic infections (patients could experience ≥1 opportunistic infection; cytomegalovirus (CMV) infection reactivation, n=4; CMV infection, n=2; cytomegalovirus oesophagitis, n=1; esophageal candidiasis, n=1; polyomavirus viraemia, n=1), of which 3.3% were grade 3/4 infections.
  • At baseline, 22.2% of patients had Ig values <400 mg/dL.
  • A total of 71.1% of patients had post-treatment hypogammaglobulinemia with post-treatment immunoglobulin G (IgG) <400 mg/dL or hypogammaglobulinemia treatment-emergent AE.
    • Of these patients, 75.6% of patients received ≥1 dose of Ig replacement.
Treatment Discontinuation
  • A total of 8.9% of patients (n=8) discontinued TALVEY or TECVAYLI due to AEs.
  • Discontinuation of both TALVEY and TECVAYLI was reported in 6 patients:
    • Not resolved: oesophageal adenocarcinoma, n=1, and AEs deemed related to TALVEY or TECVAYLI by the investigator (Hodgkin's disease, n=1; pseudomonal pneumonia and pseudomonal sepsis, n=1; dry mouth, dysphagia and decreased weight, n=1).
    • Resolved: CMV infection, n=1; immune effector cell-associated neurotoxicity syndrome (ICANS), n=1. All AEs were deemed related to TALVEY or TECVAYLI by the investigator.
  • Discontinuation of TALVEY was reported in 2 patients:
    • Resolved: dysgeusia and dysphagia, n=1; hypohidrosis, n=1.
Grade 5 AEs
  • Grade 5 AEs were reported in 12.2% of patients (n=11).
  • Of the 11 patients with EMD who experienced grade 5 AEs, 6 events were considered drug related. Seven of these patients were nonresponders and had poor overall prognosis.
  • Grade 5 infections were reported in 6.7% of patients (n=6) and grade 5 noninfection AEs were reported in 5.6% of patients (n=5). See Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Grade 5 AEs for additional details.

RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Summary of Hematologic and Nonhematologic AEs (≥30% Overall)6
AEa, %
TALVEY + TECVAYLI
(N=90)
Any grade
Maximum Grade 3/4
Hematologic AEs
   Neutropenia
72.2
63.3
   Anemia
53.3
33.3
   Thrombocytopenia
37.8
25.6
Nonhematologic AEs
   Oral AEsb
86.7
4.4
   Infections
80.0
33.3
   CRS
77.8
0
   Nonrash skin AEc
68.9
0
   Nail-related AEd
55.6
0
   Weight decrease
53.3
12.2
   Cough
40.0
0
   Diarrhea
37.8
4.4
   Nausea
32.2
0
   Hypokalemia
31.1
7.8
   Pyrexiae
31.1
1.1
   Rash-related AEf
31.1
1.1
   Fatigue
30.0
3.3
Abbreviations: AE, adverse event; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; ICANS, immune effector cell-associated neurotoxicity syndrome; RP2R, recommended phase 2 regimen.
Clinical data cutoff date of July 18, 2025. Median follow-up 16.8 months.
aAEs graded by CTCAE v5.0. AEs were reported as treatment-emergent AEs recorded up to 30 days after the patient received last study treatment dose or until start of subsequent therapy.
bIncludes ageusia, cheilitis, dry mouth, dysgeusia, dysphagia, glossitis, glossodynia, hypogeusia, mouth ulceration, oral discomfort, oral mucosal erythema, oral pain, stomatitis, swollen tongue, taste disorder, tongue discomfort, tongue erythema, tongue oedema, and tongue ulceration.
cIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
dIncludes nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging.
eExcludes symptoms of CRS or ICANS.
fIncludes rash, maculopapular rash, erythematous rash, and erythema.

RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): AEs Following Adjustment to Q4W Dosing6
Outcomea, n (%)
Initial Q2W Dosing
(N=90)
After Adjustment to Q4W Dosing
(n=56)b
Any-grade infections
65 (72.2)
34 (60.7)
   Grade ≥3 infections
29 (32.2)
14 (25.0)
Weight decrease
46 (51.1)
15 (26.8)
   Grade 3/4 weight decrease
8 (8.9)
5 (8.9)
Oral AEsc
77 (85.6)
12 (21.4)
   Grade 3/4 oral AEsc
3 (3.3)
2 (3.6)
Abbreviations: AE, adverse event; Q2W, every other week; Q4W, once every 4 weeks.
Clinical data cutoff date of July 18, 2025. Median follow-up 16.8 months.
aNew onset AEs only; AEs are only counted once either before or after switch.
bA total of 34 patients did not switch to Q4W dosing.
cIncludes ageusia, cheilitis, dry mouth, dysgeusia, dysphagia, glossitis, glossodynia, hypogeusia, mouth ulceration, oral discomfort, oral mucosal erythema, oral pain, stomatitis, swollen tongue, taste disorder, tongue discomfort, tongue erythema, tongue oedema, and tongue ulceration.

RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Infections (≥10% Overall)6
AEa, n (%)
TALVEY + TECVAYLI
(N=90)
Any Grade
Maximum Grade 3/4
Infections
72 (80.0)
30 (33.3)
   Upper respiratory tract infection
27 (30.0)
4 (4.4)
   COVID-19
20 (22.2)
5 (5.6)
   Pneumonia
19 (21.1)
8 (8.9)
   Urinary tract infection
12 (13.3)
4 (4.4)
   Viral upper respiratory tract infection
9 (10.0)
2 (2.2)
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019; CTCAE, Common Terminology Criteria for Adverse Events.
Clinical data cutoff date of July 18, 2025. Median follow-up 16.8 months.
aAEs were graded by CTCAE v5.0; patients could experience ≥1 infection.

RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Grade 5 AEs6
AE
Study Day of Death
IgG Level Prior to Death (mg/dL)
Received
≥1 Dose Ig Replacement
Response
at Time
of Death
Noninfections
   Aspirationa
15
1450
No
SD
   Respiratory failure
19
221
No
SD
   General physical  
   health deterioration
21
6731
Yes
SD
   Cerebral hemorrhage
25
2575
No
SD
   Euthanasia
233
379
Yes
PD
Infections
   Klebsiella sepsis
38
70
No
PR
   COVID-19  
   pneumoniaa,b
63
2455
No
SD
   Klebsiella pneumoniaa
86
892
Yes
PR
   Pseudomonal sepsisa
190
246
No
PR
   Escherichia sepsisa
240
449
Yes
VGPR
   Pneumoniaa
254
346
Yes
PD
Abbreviations: AE, adverse event; PD, progressive disease; PR, partial response; SD, stable disease; VGPR, very good partial response.
Clinical data cutoff date of July 18, 2025. Median follow-up 16.8 months.
aDeemed related to TALVEY or TECVAYLI by investigators.
bPatient declined COVID-19 vaccine prior to study entry.

Kumar et al (2025)8,9 published the efficacy and safety results from the RedirecTT-1 phase 2 study in patients with RRMM and EMD at a median follow-up of 12.6 months (range, 0.5-19.5).

Study Design/Methods

  • IMWG criteria do not include PET-CT-specific response criteria; adaptations were incorporated to assess extramedullary myeloma response.
    • CR was defined as disappearance of all plasmacytomas or persistence of fibrotic disease with a Deauville score of 1 to 3.
    • sCR was defined as CR plus normal free-light-chain ratio and absence of clonal plasma cells as assessed by immunohistochemistry or flow cytometry.
    • VGPR was defined as at least 90% size reduction in all plasmacytomas and reduction in FDG avidity from baseline.
    • PR was defined as at least 50% size reduction in all plasmacytomas and reduction in FDG avidity from baseline.
  • In nonsecretory disease, response was evaluated using functional imaging; IMWG criteria had to be met for complete response confirmation.
  • Extramedullary myeloma response was assessed at suspected first response and every 12 weeks thereafter until disease progression; imaging frequency could be reduced to every 16 weeks after 1 year.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

  • As of March 18, 2025, 90 patients with extramedullary myeloma had initiated study treatment.
  • The median duration of follow-up was 12.6 months (range, 0.5-19.5).
  • At the data cutoff for the primary analysis, 54% of patients (n=49) remained on treatment, including 2 patients receiving TECVAYLI monotherapy.
  • Median age was 64.5 years.
  • At a median duration of 4.7 years since diagnosis, patients had received a median of 4 prior LOTs.
  • Median number of disease sites was 2 (range, 1-7); 60% of patients (n=54) had ≥1 soft-tissue site, 39% of patients (n=35) had ≥1 lymph-node site, and 33% of patients (n=30) had ≥1 organ site.
    • Common sites included retroperitoneum, abdominal wall, and chest wall. Paramedullary disease coexisted with true extramedullary disease in 21% of patients (n=19).
  • Baseline tumor volume was <25 cm² in 54% of patients (n=49), 25-50 cm² in 21% of patients (n=19), and >50 cm² in 24% of patients (n=22).
  • Nonsecretory disease was reported in 4% of patients (n=4), and oligosecretory disease in 34% of patients (n=31).
  • Prior anti-BCMA CAR-T therapy was received by 20% of patients (n=18) and prior BsAb exposure (anti-FcRH5) was reported in 9% of patients (n=8); median time from CAR-T to study treatment was 295 days (range, 98-1030).

Efficacy

  • Efficacy outcomes are presented in Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Summary of Efficacy Outcomes.
  • Efficacy outcomes by prior therapy are presented in Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Efficacy Outcomes in Subgroups by Prior TCR Therapy.
  • Responses were consistent across clinically relevant subgroups, including patients with multiple prior LOTs, ISS stage III disease, four or more extramedullary sites at baseline, or high-risk cytogenetic profiles.
  • A total of 83% of patients (95% CI, 65–94) among patients with organ disease sites and 77% of patients (95% CI, 64-87) with nonorgan disease sites achieved a response.
  • Overall response was 82% (95% CI, 68-91) in patients with a baseline tumor volume of <25 cm², 74% (95% CI, 49-91) in patients with a tumor volume of 25-50 cm², and 77% (95% CI, 55-92) in patients with a tumor volume >50 cm².
  • At a median follow-up of 13.4 months (range, 1.2-19.5), 66% of responders remained on therapy at the data cutoff.
    • Of the 71 responders, 77% of patients (n=55) switched to monthly dosing; 93% of responses (n/N=51/55) deepened or were maintained in the first 6 months after the switch to monthly dosing.
  • After treatment with TALVEY plus TECVAYLI, 24% of patients (n=22) received ≥1 subsequent antimyeloma therapy.

RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Summary of Efficacy Outcomes8,9 
Response Ratea
TALVEY + TECVAYLI
(N=90)
ORRa, % (95% CI)
79 (69-87)
   sCR, %
43
   CR, %
11
   VGPR, %
16
   PR, %
9
≥CR, % (95% CI)
54 (44-65)
≥VGPR, % (95% CI)
70 (59-79)
Median time to first response, months (range)
2.6 (1.0-5.8)
Median time to best response, months (range)
4.7 (1.0-11.9)
Median PFS, months (95% CI)
15.4 (10.8-NE)
   12-month PFS rate, % (95% CI)
61.0 (50-71)  
Median DOR, months (95% CI)
13.8 (11.5-NE)  
   12-month DOR rate, % (95% CI)
64 (48-76)
Median OS, months (95% CI)
NR (NE-NE)
   12-month OS rate, % (95% CI)
74.5 (63.4-82.7)
Abbreviations: BsAb, bispecific antibody; CI, confidence interval; CR, complete response; DOR, duration of response; EMD, extramedullary disease; IMWG, International Myeloma Working Group; NE, not estimable; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cutoff date of March 18, 2025. Median follow-up of 12.6 months (range, 0.5-19.5).
aAssessed by independent review committee per IMWG criteria.

RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Efficacy Outcomes in Subgroups by Prior TCR Therapy8 
Response Rate
Prior Anti-BCMA CAR-T Cell Therapy
(n=18)
Prior BsAb Therapy
(n=8)
ORRa, % (95% CI)
83 (59-96)
75 (35-97)
   sCR, %
50.0
38
   CR, %
28
-
   VGPR, %
6
25
   PR, %
-
12
≥CR, % (95% CI)
78 (52-94)
38 (8-76)
≥VGPR, % (95% CI)
83 (59-96)
62 (24-91)
Median PFS, months (95% CI)
15.4 (4.9-NE)
-
   12-month PFS rate, % (95% CI)
61 (35-79.0)
-
Median DOR, months (95% CI)
13.8 (NE-NE)
-
   12-month DOR rate, % (95% CI)
72.0 (41-89)
-
Median OS, months (95% CI)
NE
-
   12-month OS rate, % (95% CI)
74 (63-83)
-
Abbreviations: BsAb, bispecific antibody; CI, confidence interval; CR, complete response; DOR, duration of response; EMD, extramedullary disease; IMWG, International Myeloma Working Group; NE, not estimable; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cutoff date of March 18, 2025. Median follow-up of 12.6 months (range, 0.5-19.5).
aAssessed by independent review committee per IMWG criteria.

Safety

Cytokine Release Syndrome
  • CRS was reported in 77.8% of patients (n=70).
  • All CRS events were grade 1 or 2 and most occurred only during the step-up dosing phase and cycle 1.
  • At data cutoff, 99% of CRS events (121 of 122) had resolved. Among patients with CRS, 97% (n=68) received supportive measures.
  • Median time from the most recent treatment dose to CRS onset was 2 days, and median CRS duration was 2 days.
Neurotoxicity
  • ICANS were reported in 12.2% of patients (n=11); most events were grade 1/2, with one grade 3 and one grade 4 event reported.
  • The grade 4 event had resolved by the data cutoff.
  • All ICANS events occurred during the step-up dosing period or the first treatment cycle, and the median duration was 2 days.
Hematologic AEs
  • Any-grade neutropenia was reported in 72% of patients (n=65); grade 3/4 neutropenia in 62% of patients (n=56).
  • Any-grade anemia was reported in 51% of patients (n=46); grade 3/4 anemia in 31% of patients (n=28).
  • Any-grade thrombocytopenia was reported in 38% of patients (n=34); grade 3/4 thrombocytopenia in 26% of patients (n=23).
Infections and Hypogammaglobulinemia
  • Any-grade infections were reported in 79% of patients (n=71) and grade 3/4 infections were reported in 31% of patients (n=28).
  • Opportunistic infections were reported in 7% of patients (n=6) and were generally confined to the first 6 months of treatment; none were fatal.
  • Grade 3/4 infections occurred within the first 6 months of treatment; incidence declined thereafter.
  • Out of the 5 patients who died due to infections, 3 did not receive intravenous immunoglobulin and 3 had immunoglobulin G levels <400 mg/dL at time of death.
  • A total of 97% of patients (n=87) received anti-herpes prophylaxis, 6% of patients (n=5) received antiviral hepatitis B prophylaxis and 82% of patients (n=74) received COVID-19 vaccination.
  • A total of 87% patients (n=78) received any intravenous immunoglobulin during the study.
  • At baseline, 22% of patients (n=20) had IgG <400 mg/dL; post-treatment, 70% of patients (n=63) had hypogammaglobulinemia or IgG <400 mg/dL.
  • Of the 63 patients, 86% of patients (n=54) received ≥1 dose of intravenous immunoglobulin (IVIG); median time from first study dose to first immune globulin dose was 50 days.
Oral AEs
  • Oral AEs included ageusia, cheilitis, dry mouth, dysgeusia (per CTCAE, the maximum grade for these events was 2) dysphagia, glossitis, glossodynia, hypogeusia, mouth ulceration, oral discomfort, oral mucosal erythema, oral pain, stomatitis, swollen tongue, taste disorder, tongue discomfort, tongue erythema, tongue oedema, and tongue ulceration.
    • Dysgeusia was reported in 70% of patients (n=63), dry mouth in 44% of patients (n=40), and dysphagia in 29% of patients (n=26). All events were low grade except for grade 3 dysphagia in 2 patients (2%); one resolved after 11 days, and one remained unresolved at data cutoff.
  • Any-grade oral AEs were reported in 86.7% of patients (n=78); grade 3/4 events were reported in 4.4% (n=4).
Nonrash Skin AEs
  • AEs included skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
  • Any-grade nonrash skin AEs were reported in 68.9% of patients (n=62); no grade 3/4 events were reported.
Rash-related AEs
  • Rash-related AEs included rash, maculopapular rash, erythematous rash, and erythema.
  • Any-grade rash-related AEs were reported in 28.9% of patients (n=26); grade 3/4 events were reported in 1.1% (n=1).
Nail-related AEs
  • AEs included nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging.
  • Any-grade nail-related AEs were reported in 55.6% of patients (n=50); no grade 3/4 events were reported.
Treeatment Discontinuation or Dose Modifications
  • A total of 6% of patients (n=5) patients reported discontinuation of treatment due to nonfatal AEs. Of these, 3% of patients experienced events that were considered by the investigator to be related to the study treatment.
  • Discontinuation due to AEs was reported in 3 patients (grade 4 pseudomonal pneumonia and grade 4 pseudomonal sepsis, n=1; grade 2 dry mouth, grade 2 dysphagia, and grade 3 decreased weight, n=1; grade 4 ICANS, n=1) for TALVEY + TECVAYLI.
  • For TALVEY only, discontinuation due to TEAEs was reported in 2 patients (grade 2 dysgeusia and grade 2 dysphagia, n=1; grade 2 hypohidrosis, n=1).
  • No patients discontinued TECVAYLI only.
  • Treatment modification due to AEs occurred in 69% of patients (n=62).
  • Treatment was modified owing to infection in 30% of patients (n=27).
  • Treatment cycles were delayed because of AEs in 61% of patients (n=55).
Mortality
  • AEs leading to death were reported in 11% of patients (n=10), of whom 7 patients had stable disease or disease progression at the time of death.
  • Treatment-related deaths (deemed by the investigator) were reported in 5 patients (COVID-19 pneumonia, klebsiella pneumonia, pneumonia [unspecified], pseudomonal sepsis, aspiration, n=1 each).
  • Deaths not considered treatment-related were reported in 5 patients (klebsiella sepsis, cerebral hemorrhage, euthanasia, general deterioration of physical health, respiratory failure, n=1 each).

RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Summary of Hematologic and Nonhematologic AEs (>30% Overall)8 
Most Common (>30% Overall) Any-Grade AEa
Hematologic
  • Neutropenia
  • Anemia
  • Thrombocytopenia
Nonhematologic
  • Oral AEsb
  • CRS
  • Nonrash skin-related AEsc
  • Nail-related AEsd
  • Weight decrease
  • Dry mouth
  • Cough
  • Diarrhea
  • Pyrexiae
  • Hypokalemia
  • Fatigue
  • Nauseae
Abbreviations: AE, adverse event; ASTCT, American Society for Transplantation and Cellular Therapy; COVID-19, coronavirus disease 2019; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events.
Clinical data cutoff date of March 18, 2025. Median follow-up of 12.6 months (range, 0.5-19.5).
aAEs were graded per CTCAE v5.0, and CRS events were graded per the ASTCT criteria. AEs were reported up to 30 days after the patient received the last dose of study treatment or until the start of subsequent antimyeloma therapy, whichever occurred first. Patients could have had multiple AEs. None of the most common AEs reported were grade 5.
bIncludes ageusia, cheilitis, dry mouth, dysgeusia (maximum severity is grade 2 according to CTCAE), dysphagia, glossitis, glossodynia, hypogeusia, mouth ulceration, oral discomfort, oral mucosal erythema, oral pain, stomatitis, swollen tongue, taste disorder, tongue discomfort, tongue edema, tongue erythema, and tongue ulceration.
cIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
dIncludes nail discoloration, nail disorder, nail dystrophy, nail ridging, nail toxicity, onychoclasis, onycholysis, and onychomadesis.
eEvents related to CRS or ICANS were not included in the reported data.

Mateos et al (2025)7 presented the efficacy and safety from phase 1b of the RedirecTT-1 study across all dose levels (dose levels 1-5), including the RP2R (dose level 5) in RRMM patients, including those with EMD.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

  • A total of 94 patients were enrolled and received TALVEY and TECVAYLI; 44 patients received the RP2R. See Table: RedirecTT-1 Study: Baseline Characteristics.
  • As of the data cutoff of July 2025, 37.2% of patients across all dose levels and 47.4% of patients at the RP2R remained on study treatment.
  • The median duration of follow-up was 38 months across all dose levels and 34.5 months for the RP2R cohort.

RedirecTT-1 Study: Baseline Characteristics7 
Characteristic
All dose levels (N=94)
RP2R
(n=44)
Median age, years (range)
64.5 (39-81)
63.0 (41-80)
Male, %
52.1
52.3
Median years since diagnosis, years (range)
6.0 (0.3-14.6)
5.5 (0.3-12.8)
Median prior lines of therapy, n (range)
4 (1-11)
4 (2-10)
True extramedullary plasmacytomas ≥1a, %
37.2
40.9
High-risk cytogeneticsb, %
45.1
47.4
Measurable disease, %
   Nonsecretory
1.1
2.3
   Oligosecretory
11.7
13.6
Exposure status, %
   Belantamab mafodotin
19.1
11.4
   CAR-T therapyc
4.3
4.5
   BsAb therapyd
8.5
4.5
Refractory status, %
   Triple class
87.2
84.1
   Penta drug
36.2
31.8
   To last line of therapy
92.6
88.6
Abbreviations: BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T-cell; EMD, extramedullary disease; FISH, fluorescence in situ hybridization; LOT, line of therapy; RP2R, recommended phase 2 regimen.
Clinical data cutoff date of July 2025. Median follow-up of 38.0 months for all doses levels and 34.5 months for the RP2R cohort.
aEMD defined as ≥1 nonradiated bone-independent soft-tissue plasmacytoma ≥2 cm in greatest dimension.
bAssessed using FISH or karyotype testing in 51 patients across all dose levels and 19 patients in RP2R. Defined as del(17p), t(4;14), or t(14;16)].
cA total of 2.1% across all doses and 4.5% in RP2R cohort received BCMA CAR-T.
dAcross all doses, 4 patients received alnuctamab, 2 patients received WV-T078, 1 patient received TECVAYLI, and 1 patient received cevostamab.

Efficacy


RedirecTT-1 Study: Efficacy Outcomes7 
Parametera
All Dose Levels
(N=94)
All RP2R (n=44)
RP2R EMD (n=18)
RP2R
Non-EMD
(n=26)
Median follow-up, months
38
34.5
ORRb, % (95% CI)
78
(68-86)
80
(65-90)
61
(36-83)
92
(75-99)
   sCR
32
39
28
46
   CR
20
23
17
27
   VGPR
22
16
17
15
   PR
3
2
-
4
≥CR
52
61
44
73
Median DOR,
months (95% CI)
NR
(34.7-NE)
NR
(36.7-NE)
NR
(6.2-NE)
NR
(36.7-NE)
   24-month DOR rate,
   % (95% CI)
68.1
(55.6-77.7)
78.4
(60.0-89.1)
61.4
(26.6-83.5)
86.4
(63.4-95.4)
   36-month DOR rate,
   % (95% CI)
58.9
(45.7-69.9)
71.3
(51.9-84.0)
61.4
(26.6-83.5)
76.7
(52.7-89.6)
Median PFS,
months (95% CI)
38.6
(21.6-NE)
NR
(21.6-NE)
21.6
(2.4-NE)
NR
(32.5-NE)
   24-month PFS rate,
    % (95% CI)
57.6
(46.5-67.2)
63.6
(47.0-76.3)
39.7
(17.0-61.8)
79.4
(57.4-90.9)
   36-month PFS rate,
   % (95% CI)
52.6
(41.5-62.6)
57.9
(41.0-71.5)
39.7
(17.0-61.8)
70.5
(47.8-84.8)
Median OS,
months (95% CI)
NR
(39.1-NE)
NR
(NE-NE)
NR
(3.9-NE)
NR
(NE-NE)
   24-month OS rate,
   % (95% CI)
68.6
(57.2-77.5)
73.9
(56.6-85.1)
57.0
(26.5-78.8)
83.2
(61.1-93.4)
   36-month OS rate,
   % (95% CI)
65.8
(54.2-75.1)
73.9
(56.6-85.1)
57.0
(26.5-78.8)
83.2
(61.1-93.4)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; EMD, extramedullary disease; IMWG, International Myeloma Working Group; NE, not estimable; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; RP2R, recommended phase 2 regimen; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cutoff date of July 2025. Median follow-up of 38.0 months for all doses levels and 34.5 months for the RP2R cohort.
aResponse was assessed by the investigator per IMWG criteria.
bAll treated patients were included in the estimation of ORR. Individual response rates may not sum to the ORR due to rounding. ORR was assessed as sCR, CR, VGPR, or PR.

Safety

Infections and Hypogammaglobulinemia
Treatment Discontinuation
Grade 5 AEs
  • Details of grade 5 AEs is presented in Table: RedirecTT-1 Study: Grade 5 Infections.
  • At RP2R, grade 5 AEs were 13.4% (n=6), including infections (n=5) and cardiac arrest (n=1).
    • Confounding factors for grade 5 infections at RP2R included absence of COVID-19 vaccination in 2 of 3 COVID-19 pneumonia cases and severe hypogammaglobulinemia in 3 of 5 cases.
  • Across all dose levels, grade 5 AEs were 19.1% (n=18), including 15 infection-related AEs.
    • At non-RP2R doses, AEs leading to death included 2 non-infectious deaths (leptomeningeal myelomatosis, n=1; myelodysplastic syndrome, n=1)

RedirecTT-1 Study: Summary of Hematologic and Nonhematologic AEs (≥30% Overall)7 
AEa, %
All Dose Levels (N=94)
Any Grade
Grade 3/4
Hematologic AE
   Neutropenia
74.5
70.2
   Anemia
57.4
40.4
   Thrombocytopenia
48.9
33.0
Nonhematologic AE
   Infectionsb
93.6
53.2
   CRS
80.9
2.1
   Oralc
78.7
1.1
   Nonrash skind
62.8
1.1
   Diarrhea
54.3
3.2
   Pyrexiae
54.3
0
   Nail relatedf
52.1
0
   Cough
51.1
1.1
   Rash related
43.6
1.1
   Weight decreaseg
36.2
8.5
Abbreviations: AE, adverse event; ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; ICANS, immune effector cell-associated neurotoxicity syndrome; RP2R, recommended phase 2 regimen.
Clinical data cutoff date of July 2025. Median follow-up of 38.0 months for all doses levels and 34.5 months for the RP2R cohort.
aAEs graded by CTCAE v5.0; CRS graded per ASTCT criteria.
bMost common infections were COVID-19 (40.4%) and upper respiratory tract infection (30.9%); patients were screened for enrollment between 2020 to 2023, concurrent with the pandemic.
cIncluding ageusia, cheilitis, dry mouth, dysgeusia, dysphagia, glossitis, glossodynia, hypogeusia, mouth ulceration, oral discomfort, oral mucosal erythema, oral pain, stomatitis, swollen tongue, taste disorder, tongue discomfort, tongue erythema, tongue edema, and tongue ulceration.
dIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
eExcludes symptoms of CRS or ICANS.
fIncludes nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging.
gIncludes rash, maculopapular rash, erythematous rash, and erythema.

RedirecTT-1 Study: Infections (≥15% Overall)7 
AE, n (%)
All Doses
(N=94)
RP2R
(n=44)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Infections
88 (93.6)
50 (53.2)
41 (93.2)
19 (43.2)
   COVID-19a
38 (40.4)
15 (16.0)
20 (45.5)
7 (15.9)
   URTI
29 (30.9)
4 (4.3)
15 (34.1)
1 (2.3)
   Pneumonia
25 (26.6)
10 (10.6)
11 (25.0)
4 (9.1)
   Nasopharyngitis
16 (17.0)
0
4 (9.1)
0
   Rhinovirus infection
16 (17.0)
3 (3.2)
6 (13.6)
0
   UTI
12 (12.8)
2 (2.1)
8 (18.2)
1 (2.3)
Abbreviations: AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; COVID-19, coronavirus disease 2019; RP2R, recommended phase 2 regimen; URTI, upper respiratory tract infection; UTI, urinary tract infection.
Clinical data cutoff date of July 2025. Median follow-up of 38.0 months for all doses levels and 34.5 months for the RP2R cohort.
aPatient recruitment began in December 2020, running concurrently with the COVID-19 pandemic and overlapping with peak infection and death rates worldwide, based on World Health Organization data.

RedirecTT-1 Study: Timing of New Onset Infections Across All Dose Levels7 
Parameter
New Onset Infection Within
Total
(N=94)
≤6 Months
(N=94)
>6 to ≤12 Months
(N=61)
>12 to ≤18 Months
(N=55)
>18 to ≤24 Months
(N=42)
> 24 to ≤36 Months
(N=38)
>36 Months
(N=23)
Any grade infectiona, n (%)
87 (92.6)
73 (77.7)
42 (68.9)
37 (67.3)
28 (66.7)
22 (57.9)
15 (65.2)
Grade ≥3
infectiona, n (%)
64 (68.1)
44 (46.8)
21 (34.4)
17 (30.9)
9 (21.4)
7 (18.4)
4 (17.4)
Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events; RP2R, recommended phase 2 regimen; TEAE, treatment-emergent adverse event.
Clinical data cutoff date of July 2025. Median follow-up of 38.0 months for all doses levels and 34.5 months for the RP2R cohort.
aIncludes patients either treated or who experienced any TEAEs of infection within the specific window. Data shown are system organ class treatment-emergent infections and infestations and graded by CTCAE v5.0.

RedirecTT-1 Study: Treatment Discontinuation Due to AEs7 
AE, n
TALVEY + TECVAYLI

TALVEY Only
Multiple organ dysfunction
1
-
Pulmonary toxicity
1
-
Odynophagia
1
-
PMLa
1
-
Leptomeningeal myelomatosis
1
-
Myelodysplastic syndrome
1
-
Gingival bleeding
-
1
Tongue discomfort
-
1
Dysgeusia
-
1
Pain in extremity
-
1
Abbreviations: AE, adverse event; PML, progressive multifocal leukoencephalopathy.
Clinical data cutoff date of July 2025. Median follow-up of 38.0 months for all doses levels and 34.5 months for the RP2R cohort.
aPML event onset occurred 301 days after the most recent dose of TALVEY + TECVAYLI.

RedirecTT-1 Study: Grade 5 Infections7 
AE
Study Day
of Death
Calendar Year of Death
Received ≥1 Dose of Ig Replacement
IgG Level Prior to Death (mg/dL)
Response at Time
of Death
At RP2R
   COVID-19 pneumoniaa
96
2022
No
109
PR
   COVID-19 pneumoniab,c
144
2022
No
159
sCR
   COVID-19 pneumoniaa
51
2022
No
596
NA
   Fungal pneumonia
57
2022
No
217
NA
   PMLc,d
661
2023
Yes
514
sCR
At non-RP2R dose levels
   Adenovirus infectiond
395
2022
Yes
16
CR
   Aspiration pneumonia
70
2022
Yes
1325
SD → NE
   CMV pneumoniaec
117
2021
No
69
VGPR
   COVID-19a
264
2021
Yes
911
PR
   PMLc,d
217
2021
Yes
823
PD → NE
   PMLc,d
296
2022
No
16
VGPR
   Respiratory tract infectiond
217
2021
No
39
CR
   Sepsisd
110
2021
No
167
PR
   Septic shockd
1274
2024
Yes
399
NE
   Septic shock
91
2021
No
153
MR
Abbreviations: IgG, immunoglobulin G; NA, not available; PML, progressive multifocal leukoencephalopathy; PR, partial response; RP2R, recommended phase 2 regimen; sCR, stringent complete response.
Clinical data cutoff date of July 2025. Median follow-up of 38.0 months for all doses levels and 34.5 months for the RP2R cohort.
aPatient did not receive COVID-19 vaccination.
bPatient received COVID-19 vaccination.
cDeemed related to TALVEY + TECVAYLI by the investigator.
dPML onset occurred 62, 5, and 226 days, respectively, after the most recent dose of TALVEY + TECVAYLI.

Cohen et al (2025)3,10 published early safety and efficacy results from the phase 1 dose-escalation segment of the RedirecTT-1 study across all dose levels (dose levels 1-5) and RP2R (dose level 5) cohorts in RRMM patients, including those with EMD.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

  • A total of 94 patients were enrolled and received TALVEY and TECVAYLI; 44 patients received the RP2R.
  • The median duration of follow-up was 20.3 months (range, 0.5-37.1) in the all dose levels and 18.2 months (range, 0.7-27.0) in the RP2R cohorts.
  • Overall, 52% of patients (n=49) across all dose levels remained on TALVEY and TECVAYLI, while 1 patient (1%) discontinued TALVEY but continued with TECVAYLI monotherapy.
  • At baseline, the median age was 64.5 years across all dose levels. Patients had received a median of 4 prior LOTs, with a median duration of 6.1 years since diagnosis.
  • A total of 65% of patients (n=61) had penta-drug exposure and 100% (n=94) had triple-class exposure across all dose levels.
  • Extramedullary plasmacytomas ≥1 and high-risk cytogenetics were reported in 36% and 41% of patients respectively.

Efficacy

Extramedullary Disease

RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Summary of Efficacy Outcomes3 
Response Rate
All Dose Levels
(N=94)
RP2R
(n=44)
ORR, n/N (%)
73/94 (78)
35/44 (80)
   sCR, %
27
30
   CR, %
21
23
   VGPR, %
27
25
   PR, %
3
2
≥CR, n (%)
45 (48)
23 (52)
≥VGPR, n (%)
70 (74)
34 (77)
DOR, % (95% CI)
   12-month DOR
86 (75-92)
91 (75-97)
   18-month DOR
77 (64-85)
86 (66-95)
Median time to first response,
months (range)
1.8 (0.3-7.7)
1.4 (0.3-5.1)
Estimated PFS, % (95% CI)
   12-month PFS
71 (60-79)
74 (57-84)
   18-month PFS
62 (51-72)
70 (52-82)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; IMWG, International Myeloma Working Group; ORR, overall response rate; PFS, progression-free survival; PR, partial response; RP2R, recommended phase 2 regimen; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cutoff date of March 15, 2024. The median follow-up time was 20.3 months (range, 0.5-37.1) and 18.2 months (range, 0.7-27.0) for the all dose levels and RP2R cohort, respectively.

RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Response Summary in Patients With EMDa,1,3
Response Rate
All Dose Levels
(N=34)
Dose Level 1-4
(n=16)
RP2R
(n=18)
ORRb, n/N (% [95% CI])
20/34
(58.8 [40.7-75.4])
9/16 (56.3)
11/18
(61.1 [35.7-82.7])
   sCR, %
-
6.3
11.1
   CR, %
-
12.5
22.2
   VGPR, %
-
25.0
27.8
   PR, %
-
12.5
0
≥CR, %
-
18.8
33.3
Median DOR, months (95% CI)
-
12.9 (1.2-NE)
NE (5.95-NE)
   12-month DOR, % (95% CI)
70 (45-85)
55.6 (-)
82 (45-95)
   18-month DOR, % (95% CI)
52 (25-74)
-
82 (45-95)
Median time to first response, months (range)
-
2.6 (2.1-3.8)
3.0 (1.4-5.1)
Median time to best response, months (range)
-
3.9 (2.1-10.7)
6.3 (3.0-10.7)
Median PFS, months, (95% CI)
-
6.1 (2.5-15.3)
NE (2.4-NE)
   12-month PFS, % (95% CI)
-
36.1 (-)
53 (28-73)
   18-month PFS, % (95% CI)
-
-
53 (28-73)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; EMD, extramedullary disease; IMWG, International Myeloma Working Group; NE, not estimable; ORR, overall response rate; PFS, progression-free survival; PR, partial response; RP2R, recommended phase 2 regimen; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cutoff date of March 15, 2024. The median follow-up time was 20.3 months (range, 0.5-37.1) for all dose levels, 18.7 months (range, 0.5-33.8 [0.5 denotes patients who died]) for dose levels 1-4, and 13.6 months (range, 0.7-25.9) for the RP2R cohorts.
aEMD defined as ≥1 nonradiated, bone-independent lesion ≥2 cm.
bResponses were assessed by the investigator per IMWG 2016 criteria. Data shown are confirmed responses and calculated in all treated patients.

Safety

  • TEAEs are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Summary of Hematologic and Nonhematologic AEs (>25% Overall).
  • A total of 3 patients had dose-limiting toxicities at dose level 1 (grade 3 oral herpes), dose level 3 (grade 3 elevated alanine aminotransaminase /aspartate aminotransferase), and at the RP2R (grade 4 thrombocytopenia).
  • Grade 3 tumor flare reaction was reported in 1 patient (1%).
  • AEs were reported as TEAEs and recorded for up to 30 days after the last dose of the study treatment.
  • The majority of pyrexia events occurring within the first 6 months of study treatment were concurrent with other AEs, including infections, CRS, and injection-site reactions.
Cytokine Release Syndrome
  • Across all dose levels (N=94), CRS events were reported in 79% of patients (n=74), including 53.2% of patients (n=50) with grade 1, 23.4% of patients (n=22) with grade 2, and 2% of patients (n=2) with grade 3 CRS; CRS was graded per ASTCT criteria.
  • Details on occurrence and management of CRS are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Incidence and Management of CRS.
  • Most CRS events occurred during step-up dosing (SUD) and early cycles of treatment administration.
Neurotoxicity
  • ICANS was reported in 3% of patients (n=3), including 1 grade 3 ICANS event; 1 patient had 2 events.
  • Two out of 4 ICANS events were concurrent with CRS. All ICANS events occurred during SUD.
  • The median time to onset of ICANS was 2.5 days; the median duration of ICANS was 3 days. All events recovered.
Hematologic AEs
  • Any-grade neutropenia was reported in 73% of patients (n=69); grade 3/4 neutropenia in 68% of patients (n=64).
  • Any-grade anemia was reported in 56% of patients (n=53); grade 3/4 anemia in 38% of patients (n=36).
  • Any-grade thrombocytopenia was reported in 43% of patients (n=40); grade 3/4 thrombocytopenia in 30% of patients (n=28).
Infections
  • Across all dose levels, any-grade infections were reported in 89% of patients (n=84) and grade 3/4 infections were reported in 64% of patients (n=60).
  • The median time to onset from the last administration of study treatment was 9 days (range, 1-89).
  • The median duration of infections was 13 days (range, 1-223).
  • 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.
  • 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.
  • In total, 63% of patients (n=59) received a COVID-19 vaccine.
  • Immunoglobulin replacement therapy (0.4 g/kg every 3-6 weeks) was recommended to maintain serum IgG levels above 400 mg/dL, regardless of current or past infections, with monitoring recommended at least every 3 months after reaching steady state.
  • Ig replacement was provided per institutional guidelines for managing serious, recurrent, or chronic infections.
  • A total of 82.5% of events (n=113; calculated with number of events as the denominator [N=137]) were recovered or resolved.
  • Dose delay or dose modification due to infections was reported in 68% of patients (n=64).
Hypogammaglobulinemia
  • At baseline, 56% of patients across all dose levels (n=53) had non-IgG myeloma.
    • Of these patients, 70% of patients (n=37) had hypogammaglobulinemia (defined as IgG <400 mg/dL) at baseline and 57% of patients (n=30) had post-treatment hypogammaglobulinemia.
  • The assessments excluded patients with IgG myeloma and those who received IVIG replacement.
  • A total of 57% of patients (n=30) with non-IgG myeloma received IVIG.
Taste-change AEs in Patients Across All Dose Levels
  • Taste-change AEs included dysgeusia, ageusia, hypogeusia, and taste disorder; per CTCAE, the maximum grade for these events was 2.
  • Any-grade taste-change AEs were reported in 64.9% of patients (n=61).
Skin-related AEs in Patients Across All Dose Levels
  • Skin-related AEs included skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
  • Skin-related AEs were reported in 60.6% of patients (n=57).
  • No grade 3/4 skin-related AEs were reported.
Rash AEs in Patients Across All Dose Levels
  • Rash AEs included rash, maculopapular rash, erythematous rash, and erythema.
  • Any-grade rash AEs were reported in 39.4% of patients (n=37).
  • Grade 3 rash AE at the RP2R was reported in 1.1% of patients (n=1).
Nail-related AEs in Patients Across All Dose Levels
  • Any-grade nail-related AEs were reported in 52.1% of patients (n=49).
  • No grade 3/4 nail-related AEs were reported.
Treatment Discontinuation or Dose Modifications
  • Cycle delays or dose modification due to AEs were reported in 93% of patients (n=87), primarily due to infections (68%, n=64).
  • A total of 7% of discontinuations (n=7) were considered by the investigator to be related to a study drug, of which 5% of discontinuations (n=5) were due to infections.
  • Discontinuation of one or both agents due to AEs was reported in 16% of patients (n=15). Details for discontinuations across dose levels are presented below:
    • In the TALVEY 0.2 mg/kg + TECVAYLI 0.75 mg/kg QW cohort (n=6), treatment discontinuation was reported due to adenovirus infection (n=1) and multiple organ dysfunction syndrome (n=1).
    • In the TALVEY 0.2 mg/kg + TECVAYLI 1.5 mg/kg QW cohort (n=5), treatment discontinuation due to pulmonary toxicity (n=1) was observed.
    • In the TALVEY 0.4 mg/kg + TECVAYLI 1.5 mg/kg QW cohort (n=28), treatment discontinuation was reported due to cytomegaloviral pneumonia (n=1), respiratory tract infection (n=1), sepsis (n=1), septic shock (n=1), and myelodysplastic syndrome (n=1).
    • In the TALVEY 0.8 mg/kg + TECVAYLI 1.5 mg/kg Q2W cohort (n=11), treatment discontinuation was reported due to aspiration pneumonia (n=1).
    • In the TALVEY 0.8 mg/kg + TECVAYLI 3.0 mg/kg Q2W cohort (n=44), treatment discontinuations were reported due to pneumonia (n=2), COVID-19 pneumonia (n=1), respiratory failure (n=1), cardiac arrest (n=1), gingival bleeding (n=1), tongue discomfort (n=1), pain in extremity (n=1), and dysgeusia (n=1).
Mortality
  • AEs leading to death were reported in 15% of patients (n=14) across all dose levels, of which 11 deaths were due to infections.
    • In the TALVEY 0.2 mg/kg + TECVAYLI 0.75 mg/kg QW cohort (n=6), AEs leading to death included adenovirus infection (n=1) and COVID-19 (n=1).
    • In the TALVEY 0.2 mg/kg + TECVAYLI 1.5 mg/kg QW cohort (n=5), no deaths due to AEs were reported.
    • In the TALVEY 0.4 mg/kg + TECVAYLI 1.5 mg/kg QW cohort (n=28), AEs leading to death included John Cunningham virus (JCV) infection (n=1), cytomegaloviral pneumonia (n=1), respiratory tract infection (n=1), sepsis (n=1), and septic shock (n=1).
    • In the TALVEY 0.8 mg/kg + TECVAYLI 1.5 mg/kg Q2W cohort (n=11), AEs leading to death included aspiration pneumonia (n=1) and leptomeningeal myelomatosis (n=1).
    • In the TALVEY 0.8 mg/kg + TECVAYLI 3.0 mg/kg Q2W cohort (n=44), AEs leading to death included pneumonia (n=2), COVID-19 pneumonia (n=1), respiratory failure (n=1), and cardiac arrest (n=1).
  • The investigator attributed 6 deaths due to a study drug, but there is insufficient evidence to confirm whether the other events were related to treatment.
  • A total of 4 patients (4%) died due to disease progression.

RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Summary of Hematologic and Nonhematologic AEs (>25% Overall)3 
Most Common (>25% Overall) Any-Grade AEa
Hematologic
  • Neutropenia
  • Anemia
  • Thrombocytopenia
Nonhematologic
  • CRS
  • Taste changesb
  • Nonrash skin AEsc
  • Nail-related AEsd
  • Pyrexiae
  • Diarrhea
  • Cough
  • Dry Mouth
  • COVID-19
  • Rash AEsf
  • Pneumonia
  • Weight decrease
  • Fatigue
Abbreviations: AE, adverse event; ASTCT, American Society for Transplantation and Cellular Therapy; COVID-19, coronavirus disease 2019; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events.
Clinical data cutoff date of March 15, 2024. The median follow-up time was 20.3 months (range, 0.5-37.1) across all dose levels.
aAEs were graded per CTCAE v5.0, and CRS events were graded per the ASTCT criteria. AEs were reported up to 30 days after the patient received the last dose of study treatment. Patients could have had multiple AEs.
bIncludes ageusia, dysgeusia, hypogeusia, and taste disorder per CTCAE v5.0; the maximum grade for taste changes is 2 per CTCAE.
cIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
dIncludes nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging.
eTwo patients had grade 3 pyrexia that was not considered by the investigators to be serious. Neither event occurred concurrently with an infection of grade 3 or higher.
fIncludes rash, maculopapular rash, erythematous rash, and erythema.

RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Incidence and Management of CRS1,3 
Parameter
All Dose Levels
(N=94)
Cycle delays or dose modification, n (%)
14 (15)
Median time to onseta, days (range)
2 (1-733)
Median duration, days (range)
2 (1-8)
Patients who received supportive measuresb, n (%)
61 (65)
   Tocilizumab
24 (26)
   Intravenous fluids
11 (11.7)
   Corticosteroids
 3 (3.2)
   Oxygen
1 (1.1)
   Vasopressor
1 (1.1)
Recovery, %
98
   Recovery with sequelae
1
   Incomplete recovery
1
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome.
Clinical data cutoff date of March 15, 2024. The median follow-up time was 20.3 months (range, 0.5-37.1) for the all dose levels cohort.
aRelative to the most recent dose.
bPatients could receive >1 supportive therapy. Other forms of supportive measures were received by 26 patients across all dose levels.

Pharmacokinetics, Pharmacodynamics, and Immunogenicity

  • At RP2R, TALVEY and TECVAYLI exposures were similar to those observed with each agent as monotherapy.
  • T-cell activation was highly variable but consistent across all dose levels.

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 19 December 2025.

 

References

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1 Cohen YC, Magen H, Gatt M, et al. Talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma: updated phase 1b results from RedirecTT-1 with >1 year of follow-up. Oral Presentation presented at: 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
2 Cohen Y, Morillo D, Gatt M, et al. First results from the RedirecTT-1 study with teclistamab + talquetamab simultaneously targeting BCMA and GPRC5D in patients with relapsed/refractory multiple myeloma. Oral presentation presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 2-6, 2023; Chicago, IL, USA/Virtual.  
3 Cohen YC, Magen H, Gatt M, et al. Talquetamab plus teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2025;392(2):138-149.  
4 Janssen Research & Development, LLC. A phase 1b/2 dose escalation and expansion study of the combination of the bispecific T cell redirection antibodies talquetamab and teclistamab in participants with relapsed or refractory multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 December 19]. Available from: https://clinicaltrials.gov/ct2/show/NCT04586426 NLM Identifier: NCT04586426.  
5 Kumar S, Mateos MV, Ye JC, et al. Phase 2 study of talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma and extramedullary disease: RedirecTT-1. Oral Presentation presented at: the 2025 European Hematology Association (EHA) Annual Meeting; June 12-15, 2025; Milan, Italy.  
6 Usmani SZ, Kumar S, Mateos MV, et al. Efficacy and safety of talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma and extramedullary disease: updated phase 2 results from the RedirecTT-1 study with extended follow-up. Oral Presentation presented at: the 67th American Society of Hematology (ASH) Annual Meeting; December 6-9, 2025; Orlando, FL.  
7 Mateos MV, Magen H, Gatt M, et al. Safety and efficacy of talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma from phase 1b of RedirecTT-1: results with an extended median follow-up of 3 years. Oral presentation presented at: the 67th American Society of Hematology (ASH) Annual Meeting; December 6-9, 2025; Orlando, FL.  
8 Kumar S, Mateos MV, Ye JC, et al. Dual targeting of extramedullary myeloma with talquetamab and teclistamab. N Engl J Med. 2025.  
9 Kumar S, Mateos MV, Ye JC, et al. Supplement to: Dual targeting of extramedullary myeloma with talquetamab and teclistamab. N Engl J Med. 2025.  
10 Cohen YC, Magen H, Gatt M, et al. Supplement to: Talquetamab plus teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2025;392(2):138-149.  
11 Cohen YC, Magen H, Gatt M, et al. Protocol to: Talquetamab plus teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2025;392(2):138-149.