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TALVEY® (talquetamab-tgvs)

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TALVEY - MonumenTAL-1 (MMY1001) Study

Last Updated: 01/30/2025

SUMMARY

  • MonumenTAL-1 (MMY1001) is an ongoing, open-label, phase 1/2 study evaluating the efficacy and safety of TALVEY in patients with relapsed or refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody.1-3
    • Rasche et al (2024)4 presented long-term follow-up efficacy and safety results from the MonumenTAL-1 study at a median follow-up of 29.8 months for the 0.4 mg/kg subcutaneous (SC) weekly (QW) cohort, 23.4 months for the 0.8 mg/kg SC once every other week (Q2W) cohort, and 20.5 months for the prior T-cell redirection therapy (TCR)-exposed cohort.
    • Jakubowiak et al (2023)5 presented the updated efficacy and safety results in patients with prior TCR, including an additional 19 patients enrolled in the MonumenTAL-1 study since the prior analysis. A total of 70 patients with prior TCR were enrolled; 67 patients (95.7%) were exposed to B-cell maturation antigen (BCMA)-targeting TCR.
    • Chari et al (2023)6 presented efficacy and safety results in patients from MonumenTAL-1 who switched to reduced or less frequent dosing with TALVEY at a data cutoff of October 11, 2023, in the responsive dose intensity reduction cohorts (n=50) and October 2, 2023, in the prospective dose intensity reduction cohort (n=19).
    • Chari et al (2022)2 published safety and efficacy of TALVEY in the phase 1 portion of the MonumenTAL-1 study in patients with RRMM. Patients received intravenous (IV) TALVEY QW or Q2W ([0.5 to 180 µg/kg] at median follow-up of 4.0 months) and at the first recommended phase 2 dose (RP2D) of 405 µg/kg SC QW cohort (at median follow-up of 11.7 months) and the second RP2D of 800 µg/kg SC Q2W cohort (at median follow-up of 4.2 months). Additional IV and SC doses were evaluated in order to select the RP2Ds.

CLINICAL DATA - Monumental-1 study - phase 2

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.7,8

The study was conducted in 3 parts; the primary objectives are listed below1:

  • Part 1 (phase 1; dose escalation): to characterize the safety of TALVEY and determine the RP2Ds and schedule.
  • Part 2 (phase 1; dose expansion): to further characterize the safety of TALVEY at the RP2Ds.
  • Part 3 (phase 2): to evaluate the efficacy of TALVEY at the RP2Ds.

Shown below is the summary of the study design and results from part 3 of the phase-2 portion of the MonumenTAL-1 study.

Study Design/Methods (Phase 2)

Patients were enrolled into 1 of the following 3 cohorts1,5:

  • TCR naive: 0.4 mg/kg SC QW, not previously exposed to TCR such as chimeric antigen receptor T-cell therapy (CAR-T) or bispecific antibodies (BsAbs; prior BCMA antibody-drug conjugate [ADC] allowed).
  • TCR naive: 0.8 mg/kg SC Q2W, not previously exposed to TCRs (prior BCMA ADC allowed).
  • Prior TCR: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W, have been previously exposed to TCRs.
    • Among the prior TCR-exposed cohort, patients were divided based on type of TCR (CAR-T, BsAb or CAR-T and BsAb).
  • Key eligibility criteria (Part 3; Phase 2):
    • Measurable multiple myeloma (MM).5
    • ≥3 prior lines of therapy including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.5
    • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.5
  • Key exclusion criteria (Part 3; Phase 2):
    • Prior grade 3 or higher cytokine release syndrome (CRS; per Lee criteria 20149) related to any TCR or any prior G protein-coupled receptor class C group 5 member D (GPRC5D)-targeting therapy.3
    • Received cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within 14 days prior to study drug (not including premedication).3
  • Primary endpoint: overall response rate (ORR).1
  • Key secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival, safety, immunogenicity, and pharmacodynamics.1
  • Dosing
    • TALVEY 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W treatment dose schedule is based on a 28-day cycle.3
    • Step-up dosing for 0.4 mg/kg SC QW3:
      • Week 1: step-up doses of TALVEY (0.01 mg/kg and 0.06 mg/kg SC).
      • Cycles 1+: TALVEY 0.4 mg/kg SC QW until progressive disease or unacceptable toxicity.
    • Step-up dosing for 0.8 mg/kg SC Q2W3:
      • Week 1: step-up doses of TALVEY (0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg SC).
      • Cycles 1+: TALVEY 0.8 mg/kg SC Q2W until progressive disease or unacceptable toxicity.
    • Premedications: dexamethasone, acetaminophen, and diphenhydramine were required to be administered for each step-up dose, and for the first full treatment dose of TALVEY.3
    • Patients were required to be hospitalized for at least 48 hours from the start of the injection, for each step-up dose and the first full treatment dose of TALVEY.3

Schinke et al (2023)1 presented the efficacy and safety results from the phase 2 portion of the MonumenTAL-1 study at a median follow-up of 18.8 months for the 0.4 mg/kg SC QW cohort, 12.7 months for the 0.8 mg/kg SC Q2W cohort, and 14.8 months for the prior TCR cohort. Rasche et al (2024)4 presented longer term follow-up efficacy and safety results in patients receiving TALVEY at a median follow-up of 29.8 months for the 0.4 mg/kg SC QW cohort, 23.4 months for the 0.8 mg/kg SC Q2W cohort, and 20.5 months for the prior TCR cohort. Efficacy and safety results for the latest follow-up are summarized below.

Results

Patient Characteristics
  • The baseline patient and disease characteristics from MonumenTAL-1 at a median duration of follow-up of 18.8 months for the 0.4 mg/kg SC QW cohort, 12.7 months for the 0.8 mg/kg SC Q2W cohort, and 14.8 months for the prior TCR cohort are presented in Table: MonumenTAL-1 Study: Baseline Patient and Disease Characteristics.1
  • Baseline characteristics at longer follow-up analysis across the QW, Q2W, and prior TCR cohorts were similar, except for a higher proportion of African American patients (9%; [n/N=32/375]).4

MonumenTAL-1 Study: Baseline Patient and Disease Characteristics1
Characteristic
0.4 mg/kg SC QW
(n=143)
0.8 mg/kg SC Q2W
(n=145)
Prior TCR
(n=51)
Median age, years (range)
67.0 (46-86)
67.0 (38-84)
61.0 (38-78)
Median time since diagnosis (range), years
6.7 (1.4-20.8)
6.4 (0.8-25.4)
6.3 (1.7-19.6)
Male, n (%)
78 (54.5)
83 (57.2)
31 (60.8)
Bone marrow plasma cells ≥60%a,n (%)
17 (12.3)
32 (22.7)
8 (17.0)
Extramedullary plasmacytomas ≥1b,n (%)
33 (23.1)
37 (25.5)
16 (31.4)
High-risk cytogeneticsc,n (%)
41 (31.1)
37 (28.9)
18 (40.9)
ISS staged,n (%)
   I
62 (43.4)
64 (44.4)
24 (47.1)
   II
53 (37.1)
45 (31.3)
18 (35.3)
   III
28 (19.6)
35 (24.3)
9 (17.6)
Median prior lines of therapy (range)
5 (2-13)
5 (2-17)
6 (3-15)
Exposure status, n (%)
   Triple-classe
143 (100)
145 (100)
51 (100)
   Penta-drugf
105 (73.4)
101 (69.7)
40 (78.4)
   BsAb
-
-
18 (35.3)g
   CAR-T
-
-
36 (70.6)h
   BsAb + CAR-T
-
-
3 (6.0)
   Belantamab
22 (15.4)
16 (11.0)
6 (11.8)
Refractory status, n (%)
   Triple-classe
106 (74.1)
100 (69.0)
43 (84.3)
   Penta-drugf
42 (29.4)
34 (23.4)
21 (41.2)
   To last line of therapy
134 (93.7)
137 (94.5)
31 (60.8)
   PIi
114 (79.7)
120 (82.8)
46 (90.2)
   Immunomodulatory drugj
133 (93.0)
130 (89.7)
49 (96.1)
   Anti-CD38 mAbk
133 (93.0)
134 (92.4)
49 (96.1)
   Belantamab
18 (12.6)
13 (9.0)
4 (7.8)
Abbreviations: BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T-cell therapy; CD38, cluster of differentiation 38; ISS, International Staging System; mAb, monoclonal antibody; PI, proteasome inhibitor; Q2W, once every other week; QW, weekly; SC, subcutaneous; TCR, T-cell redirection therapy.
Clinical data cutoff date of January 17, 2023.
aMaximum value from bone marrow biopsy or bone marrow aspirate is selected if both the results are available. Percentages are calculated from n=138 for the 0.4 mg/kg SC QW cohort, n=141 for the 0.8 mg/kg SC Q2W cohort, and n=38 for the prior TCR cohort.
bSoft tissue plasmacytomas not associated with the bone were included.
cdel(17p), t(4;14), and/or t(14;16); calculated from n=132 for the 0.4 mg/kg SC QW cohort, n=128 for the 0.8 mg/kg SC Q2W cohort, and n=44 for the prior TCR cohort.
dISS staging is derived based on serum β2-microglobulin and albumin. Percentages calculated from n=144 for the 0.8 mg/kg SC Q2W cohort.
e≥1 PI, ≥1 immunomodulatory drug, and ≥1 anti-CD38 mAb.
f≥2 PIs, ≥2 immunomodulatory drugs, and ≥1 anti-CD38 mAb.
gSixteen patients received a BCMA-directed BsAb.
hThirty-four patients received a BCMA-directed CAR-T.
iBortezomib, carfilzomib, and/or ixazomib.
jThalidomide, lenalidomide, and/or pomalidomide.
kDaratumumab, isatuximab, and/or an investigational anti-CD38 mAb.
Efficacy

MonumenTAL-1 Study: Efficacy Outcomes4
Parameter
0.4 mg/kg SC QW
(n=143)
0.8 mg/kg SC Q2W
(n=154)
Prior TCR
(n=78)
Median follow-up, months
29.8
23.4
20.5
ORRa, %
74.1
69.5
66.7
   sCR
23.1
31.2
32.1
   CR
9.8
9.1
10.3
   VGPR
26.6
18.8
12.8
   PR
14.7
10.4
11.5
≥VGPR, %
59.4
59.1
55.1
Median DOR, months, (95% CI)b
9.5 (6.7-13.4)
17.5 (12.5-NE)
NAc
   Median DOR in patients with
   ≥CR, months (95% CI)
28.6 (19.4-NE)
NR (21.2-NE)
NAc
Median PFS, months (95% CI)
7.5 (5.7-9.4)
11.2 (8.4-14.6)
7.7 (4.1-14.5)
24-month OS rate, %
(95% CI)
60.6 (51.7-68.4)
67.1 (58.3-74.4)
57.3 (43.5-68.9)
Median time to first response, months (range)
1.2 (0.2-10.9)
1.3 (0.2-4.9)
1.2 (0.2-7.5)
Median time to VGPR as best
response, months (range)
2.2 (0.8-6.2)
2.3 (0.3-18.9)
1.8 (0.8-6.4)
Median time to ≥CR as best response, months (range)
3.0 (1.1-12.7)
5.8 (1.2-16.8)
2.7 (1.2-18.7)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; NA, not available; NE, not estimable; NR, not reported; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; Q2W, once every other week; QW, weekly; SC, subcutaneous; sCR, stringent complete response; TCR, T-cell redirection therapy; VGPR, very good partial response.
Clinical data cutoff date of January 29, 2024.
aAssessed by independent review committee using International Myeloma Working Group criteria. Due to rounding, individual response rates may not sum to the ORR.
bn=106 (QW), n=107 (Q2W), and n=52 (prior TCR).
cNR due to heavy censoring from 12 to 20 months; the estimate may not be reliable at this time point.

MonumenTAL-1 Study: Time to First Confirmed Response per IRC (A) and DOR by Depth of Response (B) in the Q2W Cohort4

A screenshot of a computer Description automatically generated

Abbreviations: CR, complete response; DOR, duration of response; IRC, independent review committee; PR, partial response; Pts, patients; Q2W, once every other week; VGPR, very good partial response; mo, months.
Clinical data cutoff date of January 29, 2024.


MonumenTAL-1 Study: ORR Among High-Risk Subgroups4
ORR in Subgroups, % (95% CI)
0.4 mg/kg SC QW (n=143)
0.8 mg/kg SC Q2W (n=154)
Prior TCR
(n=78)
Median age ≥75 years, (range)
71.4 (47.8-88.7)
75.8 (57.7-88.9)
80.0 (28.4-99.5)
High-risk cytogeneticsa
70.7 (54.5-83.9)
75.0 (58.8-87.3)
52.0 (31.3-72.2)
ISS stage III
64.3 (44.1-81.4)
59.5 (42.1-75.2)
76.9 (46.2-95.0)
Baseline renal function,
≤60 mL/min/1.73 m2
65.0 (48.3-79.4)
65.2 (49.8-78.6)
63.2 (38.4-83.7)
Refractory status
   Triple-classb
72.9 (63.4-81.0)
67.3 (57.7-75.9)
65.2 (52.4-76.5)
   Penta-drugc
71.1 (55.7-83.6)
69.2 (52.4-83.0)
58.8 (40.7-75.4)
Extramedullary plasmacytomas, ≥1d
48.5 (30.8-66.5)
41.5 (26.3-57.9)
44.0 (24.4-65.1)
Abbreviations: CD, cluster of differentiation; CI, confidence interval; ISS, International Staging System; mAb, monoclonal antibody; ORR, overall response rate; PI, proteasome inhibitor; Q2W, once every other week; QW, weekly; SC, subcutaneous; TCR, T-cell redirection therapy.
Note: Data are reported from phase 2 only.
aDefined by del(17p), t(4;14), and/or t(14;16).
b≥1 PI, ≥1 immunomodulatory drug, and ≥1 anti-CD38 mAb.
c≥2 PIs, ≥2 immunomodulatory drugs, and ≥1 anti-CD38 mAb.
dSoft tissue plasmacytomas not associated with the bone were included.

MonumenTAL-1 Study: Efficacy Outcomes in the USPI Population4
Parameter
0.4 mg/kg SC QW
(n=100)
0.8 mg/kg SC Q2W
(n=87)
Prior TCRa
(n=32)
ORR, %
73.0
71.3
75.0
   VGPR
22.0
18.4
12.5
   PR
16.0
9.2
12.5
≥CR, %
35.0
43.7
50.0
Median time to first responseb, months (range)
1.2 (0.2-10.9)
1.3 (0.2-3.6)
1.1 (0.2-6.4)
Median time to best responseb, months (range)
2.1 (1.1-12.7)
4.7 (0.3-18.9)
2.1 (1.1-14.8)
   ≥CRc
2.3 (1.1–12.7)
6.4 (1.9-16.8)
4.4 (1.2-14.8)
   VGPRd
2.0 (1.1-6.2)
3.1 (0.3-18.9)
2.0 (1.3-2.1)
   PRe
1.3 (1.1-2.9)
2.1 (1.2-2.8)
1.1 (1.1-1.4)
Median DORb, months (95% CI)
10.2 (6.6-15.7)
18.0 (14.8-NE)
15.8 (3.7-NE)
   ≥CRc
28.6 (18.9-NE)
NR (21.2-NE)
24.1 (11.2-NE)
   VGPRd
6.4 (4.4-9.5)
9.3 (7.4-16.8)
4.3 (2.1-NE)
   PRe
3.0 (1.9-5.6)
4.2 (0.9-NE)
2.4 (1.9-NE)
Median PFS, months (95% CI)
6.8 (5.5-10.4)
12.5 (9.6-18.3)
6.8 (3.4-22.2)
   24-month PFS, %
21.0 (13.4-29.7)
31.1 (20.1-42.8)
28.9 (13.9-45.9)
Median OS, months (95% CI)
32.1 (21.7-NE)
NR (24.4-NE)
24.3 (7.6-NE)
   24-month OS rate, %
60.3 (49.8-69.4)
67.7 (55.2-77.4)
51.6 (32.7-67.6)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; NE, not estimable; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; Q2W, once every other week; QW, weekly; SC, subcutaneous; sCR, stringent complete response; TCR, T-cell redirection therapy; VGPR, very good partial response.
Note: Data are reported from phase 2 only.
aPhase 2 data includes the 0.4 mg/kg QW cohort only.
bn=73 (QW), n=62 (Q2W), and n=24 (prior TCR).
cn=35 (QW), n=38 (Q2W), and n=16 (prior TCR).
dn=22 (QW), n=16 (Q2W), and n=4 (prior TCR).
en=16 (QW), n=8 (Q2W), and n=4 (prior TCR).
Safety
  • Details on GPRC5D-associated adverse events (AEs) including information on dose reductions and discontinuations are presented in Table: MonumenTAL-1 Study: GPRC5D-Associated AEs.
    • One additional patient discontinued treatment due to GPRC5D-associated AEs since earlier follow-up.
  • Weight loss as assessed by vital signs was observed in 39%, 34%, and 39% of patients in the QW, Q2W, and prior TCR cohorts, respectively.
  • No increase in grade 3/4 infections was observed with longer follow-up duration.
  • IV immunoglobulin was required in 16%, 14%, and 24% of patients in the QW, Q2W, and prior TCR cohorts, respectively.
  • Overall rates of dose reductions due to AEs were 15%, 10%, and 12% and discontinuations due to AEs were 5%, 10%, and 5% in the QW, Q2W, and prior TCR cohorts, respectively.
  • No treatment-related deaths were reported.

MonumenTAL-1 Study: GPRC5D-Associated AEs4
AE (any grade), n (%)
0.4 mg/kg SC QW (n=143)
0.8 mg/kg SC Q2W (n=154)
Prior TCR
(n=78)
Taste-relateda
   Total
103 (72.0)
110 (71.4)
59 (75.6)
   Leading to dose reduction
10 (7.0)
6 (3.9)
4 (5.1)
   Leading to discontinuation
0 (0.0)
3 (1.9)
0 (0.0)
Skin-relatedb
   Total
81 (56.6)
113 (73.4)e
50 (64.1)
   Leading to dose reduction
5 (3.5)
1 (0.6)
2 (2.6)
   Leading to discontinuation
2 (1.4)
1 (0.6)
0 (0.0)
Nail-relatedc
   Total
79 (55.2)
82 (53.2)
46 (59.0)
   Leading to dose reduction
1 (0.7)
1 (0.6)
1 (1.3)
   Leading to discontinuation
0 (0.0)
0 (0.0)
0 (0.0)
Rash-relatedd
   Total
57 (39.9)f
46 (29.9)g
25 (32.1)h
   Leading to dose reduction
1 (0.7)
1 (0.6)
0 (0.0)
   Leading to discontinuation
0 (0.0)
0 (0.0)
0 (0.0)
Abbreviations: AE, adverse event; GPRC5D, G protein-coupled receptor class C group 5 member D; Q2W, once every other week; QW, weekly; SC, subcutaneous; TCR, T-cell redirection therapy.Clinical data cutoff date of January 29, 2024.
aIncluding ageusia, dysgeusia, hypogeusia, and taste disorder.
bIncluding skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
cIncluding nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging.
dIncluding rash, maculo-papular rash, erythematous rash, and erythema.
eIncluding 1 (0.6%) grade 3/4 events.
fIncluding 2 (1.4%) grade 3/4 events.
gIncluding 8 (5.2%) grade 3/4 events.
hIncluding 2 (2.6%) grade 3/4 events.

MonumenTAL-1 Study: Weight Loss in Patients With Oral Toxicitya in the QW and Q2W Cohorts4

A graph with numbers and lines Description automatically generated

Abbreviations: C, cycle; D, day; No, number; Pts, patients; Q2W, once every other week; QW, weekly; SD, step-up dose; SE, standard error.
Clinical data cutoff date of January 29, 2024.
aIncluding dysgeusia, ageusia, taste disorder, hypogeusia, dry mouth, dysphagia, cheilitis, glossitis, glossodynia, mouth ulceration, oral discomfort, oral mucosal erythema, oral pain, stomatitis, swollen tongue, tongue discomfort, tongue erythema, tongue edema, tongue ulceration.

Jakubowiak et al (2023)5 presented the updated efficacy and safety results in patients with prior TCR, including an additional 19 patients enrolled in the MonumenTAL-1 study since the prior analysis.

Study Design/Methods

  • As of October 11, 2023, 70 patients with prior exposure to TCR were enrolled, of whom 8 patients were also previously exposed to BCMA ADC.

Results

Patient Characteristics

MonumenTAL-1 Study: Baseline Characteristics (Prior TCR)5
Characteristic, n (%)
0.4 mg/kg SC QW
(n=62)
0.8 mg/kg SC Q2W
(n=8)
Overall
(N=70)
Age <65 years
38 (61.3)
6 (75.0)
44 (62.9)
Male
40 (64.5)
5 (62.5)
45 (64.3)
Bone marrow plasma cells ≥60%
10 (16.1)
0
10 (14.3)
Extramedullary plasmacytomas ≥1a
17 (27.4)
4 (50.0)
21 (30.0)
High-risk cytogeneticsb
21 (33.9)
3 (37.5)
24 (34.3)
ISS stagec
   I
29 (46.8)
4 (50.0)
33 (47.1)
   II
23 (37.1)
2 (25.0)
25 (35.7)
   III
10 (16.1)
2 (25.0)
12 (17.1)
Exposure status
   CAR-T
46 (74.2)
4 (50.0)
50 (71.4)
      BCMA CAR-T
44 (71.0)
4 (50.0)
48d (68.6)
   BsAb
21 (33.9)
4 (50.0)
25 (35.7)
      BCMA BsAb
19 (30.6)
4 (50.0)
23d (32.9)
   ADC (belantamab)
8 (12.9)
0
8 (11.4)
   ≥4 prior LOT
58 (93.5)
7 (87.5)
65 (92.9)
Refractory statuse
   Triple-classf
51 (82.3)
8 (100.0)
59 (84.3)
   Penta-drugg
27 (43.5)
4 (50.0)
31 (44.3)
   To last LOT
36 (58.1)
6 (75.0)
42 (60.0)
Abbreviations: ADC, antibody-drug conjugate; BCMA, B-cell maturation antigen; BsAb, bispecific antibody;
CAR-T, chimeric antigen receptor T-cell therapy; CD38, cluster of differentiation 38; ISS, International Staging System; LOT, line of therapy; mAb, monoclonal antibody; PD, progressive disease; PI, proteasome inhibitor; Q2W, once every other week; QW, weekly; SC, subcutaneous; SD, stable disease; TCR, T-cell redirection therapy.
aSoft tissue plasmacytomas not associated with the bone were included.
bt(14;16), t(4;14), and/or del(17p).
cISS staging is derived based on serum β2-microglobulin and albumin.
dFour patients received both BCMA CAR-T and BCMA BsAb.
ePatients were considered refractory to a LOT if the best response was SD or PD, or if they progressed ≤60 days after end of treatment. The end of treatment for CAR-T was considered the final day of CAR-T-cell infusion.
f≥1 PI, ≥1 immunomodulatory drug, and ≥1 anti-CD38 mAb.
g≥2 PIs, ≥2 immunomodulatory drug, and ≥1 anti-CD38 mAb.
Efficacy

MonumenTAL-1 Study: Efficacy Outcomes by Prior BCMA Groups (Prior TCR)5
Parameter
Overall Prior TCR
(N=70)
Prior BCMA CAR-T
(n=48a)
Prior BCMA BsAb
(n=23a)
ORRb, n (%)
47 (67.1)
35 (72.9)
13 (56.5)
   sCR, %
32.9
37.5
17.4
   CR, %
8.6
8.3
17.4
   VGPR, %
14.3
12.5
13.0
   PR, %
11.4
14.6
8.7
≥VGPR, %
55.7
58.3
47.8
Median follow-upc, months
18.4
18.4
16.3
12-month PFS rate, % (95% CI)
44.1 (32.1-55.4)
50.0 (34.9-63.4)
30.4 (13.5-49.3)
12-month DOR rate, % (95% CI)
55.2 (39.3-68.5)
54.7 (36.0-70.0)
43.3 (16.3-67.9)
Abbreviations: BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T-cell therapy; CI, confidence interval; CR, complete response; DOR, duration of response; ORR, overall response rate; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; TCR, T-cell redirection therapy; VGPR, very good partial response.
aFour patients received both BCMA CAR-T and BCMA BsAb.
bDue to rounding, individual response rates may not sum to the ORR.
cBased on Kaplan-Meier product limit estimate.

MonumenTAL-1 Study: ORR and 12-Month DOR Rate by Interval (Prior TCR)5
Time From Last Dose of Prior BCMA TCR to First Dose of TALVEY
ORR,
% (n/N)
12-Month DOR Rate,
% (95% CI)
BCMA CAR-T
<9 months
93.8 (15/16)
57.1 (27.5-78.5)
≥9 months
62.5 (20/32)
53.0 (28.6-72.4)
BCMA BsAb
<9 months
50.0 (8/16)
50.0 (15.2-77.5)
≥9 months
71.4 (5/7)
26.7 (1.0-68.6)
Abbreviations: BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T-cell therapy; CI, confidence interval; DOR, duration of response; ORR, overall response rate; TCR, T-cell redirection therapy.

MonumenTAL-1 Study: ORR by Prior LOT Before TALVEY (Prior TCR)5
LOTs Before First Dose of TALVEY
ORR, % (n/N)
CAR-T
As last LOT
75.9 (22/29)
Prior to last LOT
71.4 (15/21)
BsAb
As last LOT
28.6 (2/7)
Prior to last LOT
66.7 (12/18)
Abbreviations: BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T-cell therapy; LOT, line of therapy; ORR, overall response rate; TCR, T-cell redirection therapy.
Safety
  • A summary of select AEs in patients with prior TCR is presented in Table: MonumenTAL-1 Study: Summary of Select AEs (Prior TCR).
    • Patients with prior exposure to CAR-T had similar rates of infections, cytopenias, CRS, and GPRC5D-related AEs (dysgeusia and skin-, nail-, and rash-related AEs) compared to patients with prior exposure to BsAb.

MonumenTAL-1 Study: Summary of Select AEs (Prior TCR)5
AEs, n (%)
Overall Prior TCR
(N=70)
Prior CAR-T
(n=50)
Prior BsAb
(n=25)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Infections
51 (72.9)
18 (25.7)
37 (74.0)
12 (24.0)
18 (72.0)
7 (28.0)
Cytopeniasa
53 (75.7)
47 (67.1)
39 (78.0)
34 (68.0)
19 (76.0)
18 (72.0)
CRS
51 (72.9)
1 (1.4)
35 (70.0)
1 (2.0)
19 (76.0)
0
Dysgeusiab
53 (75.7)
NA
36 (72.0)
NA
20 (80.0)
NA
Skin relatedc
44 (62.9)
0
30 (60.0)
0
17 (68.0)
0
Nail relatedd
41 (58.6)
0
29 (58.0)
0
14 (56.0)
0
Rash relatede
23 (32.9)
2 (2.9)
14 (28.0)
2 (4.0)
9 (36.0)
0
Abbreviations: AE, adverse event; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T-cell therapy; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; NA, not applicable; TCR, T-cell redirection therapy.
aIncluding anemia, febrile neutropenia, lymphopenia, neutropenia, and thrombocytopenia.
bIncluding ageusia, dysgeusia, hypogeusia, and taste disorder. Per CTCAE, the maximum possible grade of dysgeusia is 2.
cIncluding skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia.
dIncluding nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging.
eIncluding rash, maculopapular rash, rash erythematous, and erythema.

Chari et al (2023)6 presented efficacy and safety results in patients in MonumenTAL-1 who switched to reduced or less frequent dosing with TALVEY.

Study Design/Methods

  • Patients were treated at the RP2Ds and reduced dose once they achieved a response.
  • Patients were divided into the Responsive Dose Intensity Reduction Cohorts and the Prospective Dose Intensity Reduction Cohorts:
    • Responsive Dose Intensity Reduction Cohorts (n=50); after treatment at the RP2Ds, patients received reduced dose or less frequent dose. Patients had ≥partial response (PR), treatment-emergent AE (TEAE) mitigation or both:
      • In TCR-naïve TALVEY 0.4 mg/kg QW cohort: 25 patients received a reduced dose or a less frequent dose.
      • In TCR-naïve TALVEY 0.8 mg/kg Q2W cohort: 15 patients received a reduced dose or a less frequent dose.
      • In the prior TCR TALVEY 0.4 mg/kg QW or 0.8 mg/kg Q2W cohort: 10 patients received a reduced dose or less frequent dose.
    • Prospective Dose Intensity Reduction Cohorts (n=19):
      • TALVEY 0.8 mg/kg Q2W was reduced to 0.4 mg/kg Q2W in 9 patients who had ≥PR.
      • TALVEY 0.8 mg/kg Q2W was reduced to 0.8 mg/kg once every 4 weeks in 10 patients who had ≥PR.

Results

Efficacy
  • Responsive Dose Intensity Reduction Cohorts: At a data cutoff date of October 11, 2023, most patients with dose reductions were in response. Relative to treatment start, dose reduction occurred at a median of 3.2 months (range, 1.8-27.0) in the QW cohort, 4.5 months (range, 1.2-28.9) in the Q2W cohort and 4.7 months (range, 2.3-9.7) in the prior TCR cohort. Full details are provided in Table: MonumenTAL-1 Study: DOR (Responsive Dose Intensity Reduction Cohorts).
  • Prospective Dose Intensity Reduction Cohorts: At a data cutoff of October 2, 2023, patients with dose reductions had to be in response (n=19). Relative to treatment start, dose reduction occurred at a median of 3.1 months (range, 2.3-4.2).  Full details are provided in Table: MonumenTAL-1 Study: Response and DOR (Prospective Dose Intensity Reduction Cohorts).

MonumenTAL-1 Study: DOR (Responsive Dose Intensity Reduction Cohorts)6
Responders With Dose Reductions
QWa (n=24)
Q2Wb (n=13)
Prior TCRc (n=10)
Median follow-up, months (range)
27.6 (2.7-41.2)
20.8 (12.3±33.6)
21.3 (9.2-29.4)
Median DOR, months (95% CI)
19.8 (12.7-NE)
NE (12.5-NE)
24.2 (20.4-NE)
12-month DOR rate, % (95% CI)
78.3 (55.4-90.3)
84.6 (51.2-95.9)
100.0 (100.0-100.0)
Abbreviations: AE, adverse event; CI, confidence interval; DOR, duration of response; NE, not estimable; Q2W, once every other week; QW, weekly; TCR, T-cell redirection therapy.
aPatients who dose reduced due to AE (n=21); patients who dose reduced due to response only (n=3).
bPatients who dose reduced due to AE (n=11); patients who dose reduced due to response only (n=2).
cPatients who dose reduced due to AE (n=9); patients who dose reduced due to response only (n=1).

MonumenTAL-1 Study: Response and DOR (Prospective Dose Intensity Reduction Cohorts)6
Prospective Cohorts
(n=19)
Median follow-up, months (range)a
13.2 (4.0±16.1)
Median PFS, months (95% CI)a
13.2 (8.8-NE)
   12-month PFS rate, % (95% CI)a
50.1 (27.9-68.7)
Median DOR, months (95% CI)
NE (8.3-NE)
ORR, n (%)
19 (79.2)a
   sCR, %
25.0a
   CR, %
29.2a
   VGPR, %
20.8a
   PR, %
4.2a
≥VGPR, %
75.0a
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; NE, not estimable; ORR, overall response rate; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cutoff date of October 2, 2023.
aBased on all patients included in the cohorts (N=24).
Safety

MonumenTAL-1 Study: Prospective Cohorts With Change in AE Status After Switch vs Matched Cohort Without Dose Reductiona,6

Abbreviations: AE, adverse event; DR, dose reduction; PR, partial response.
Clinical data cutoff date of October 2, 2023.
aPatients included had ≥PR before day 200 from the prospective dose intensity reduction cohorts (n=18) and from the MonumenTAL-1 cohort who did not dose reduce (n=206). Each category shows only patients who had a respective AE on day 100. Color signifies how that respective AE grade changed from day 100 to last day of follow-up (within 30 days of last treatment; capped at 500 days).

Immune Fitness in Dose-Reduced Cohorts
  • As of October 2, 2023, maintenance of CD3+ T-cell recovery was comparable between dose-reduced and non-dose-reduced cohorts between cycle 3 day 1 and cycle 7 day 1 of TALVEY (12/68 patients from the RP2D group included in the analysis had dose reductions outside the cycle 3 day 1 and cycle 7 day 1 timeframe).
  • Reduction in coinhibitory receptor expression in dose-reduced vs sustained expression in non-dose-reduced cohorts between cycle 3 and cycle 7 of TALVEY was observed.

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 27 January 2025.

 

References

Show
1 Schinke CD, Touzeau C, Minnema MC, et al. Pivotal phase 2 MonumenTAL-1 results of talquetamab, a GPRC5DxCD3 bispecific antibody, for relapsed/refractory multiple myeloma. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 2-6, 2023; Chicago, IL/Virtual.  
2 Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. 2022;387(24):2232-2244.  
3 Data on File. Talquetamab. Protocol 64407564MMY1001. Janssen Research & Development, LLC. EDMS-RIM-856432; version 22.0; 2021.  
4 Rasche L, Schinke C, Touzeau C, et al. Long-term efficacy and safety results from the phase 1/2 MonumenTAL-1 study of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma. Poster presented at: The European Hematology Association (EHA) 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.  
5 Jakubowiak AJ, Anguille S, Karlin L, et al. Updated results of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma with prior exposure to T-cell redirecting therapies: results of the phase 1/2 MonumenTAL-1 study. Poster presented at: The 65th American Society of Hematology (ASH) Annual Meeting; December 9-12, 2023; San Diego, CA/Virtual.  
6 Chari A, Oriol A, Krishnan A, et al. Efficacy and safety of less frequent/lower intensity dosing of talquetamab in patients with relapsed/refractory multiple myeloma: results from the phase 1/2 MonumenTAL-1 study. Oral Presentation presented at: The 65th American Society of Hematology (ASH) Annual Meeting; December 9-12, 2023; San Diego, CA.  
7 Janssen Research & Development, LLC. A phase 1, first-in-human, open-label, dose escalation study of talquetamab, a humanized GPRC5D x CD3 bispecific antibody, in subjects with relapsed or refractory multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 January 27]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03399799 NLM Identifier: NCT03399799.  
8 Janssen Research & Development, LLC. A phase 1/2, first-in-human, open-label, dose escalation study of talquetamab, a humanized GPRC5D x CD3 bispecific antibody, in subjects with relapsed or refractory multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 January 27]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04634552 NLM Identifier: NCT04634552.  
9 Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-195.