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TALVEY® (talquetamab-tgvs)

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TALVEY - MonumenTAL-1 (MMY1001) Study

Last Updated: 04/11/2025

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 (LOTs), including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody.1-3
    • Chari et al (2025)3,4 published a post hoc analysis with a longer-term follow-up that evaluated the efficacy and safety of TALVEY at the recommended phase 2 dose (RP2D) at a median follow-up of 25.6 months (interquartile range [IQR], 8.5-25.9) for the 0.4 mg/kg subcutaneous (SC) weekly (QW) cohort, 19.4 months (IQR, 9.2-20.7) for the 0.8 mg/kg SC every other week (Q2W) cohort, and 16.8 months (IQR, 7.6-18.7) for the prior T-cell redirection therapy (TCR)-exposed cohort from phases 1 and 2 of the MonumenTAL-1 study.
    • Rasche et al (2024)5 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 SC QW cohort, 23.4 months for the 0.8 mg/kg SC Q2W cohort, and 20.5 months for the prior TCR-exposed cohort.
    • 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)2,7 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 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.8,9

Study Design/Methods (Phase 2)

Patients were enrolled into 1 of the following 3 cohorts1,10:

  • 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 B-cell maturation antigen (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 exposed: 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 criteria3:
    • ≥18 years of age, measurable multiple myeloma (MM) per International Myeloma Working Group (IMWG) criteria.
    • ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
    • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.
  • Key exclusion criteria7:
    • Prior grade 3 or higher cytokine release syndrome (CRS; per Lee criteria 201411) related to any TCR or any prior G protein-coupled receptor class C group 5 member D (GPRC5D)-targeting therapy.
    • Central nervous system (CNS) or clinical signs of meningeal involvement of MM.
    • Received cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within 14 days prior to study drug (not including premedication).
  • Primary endpoint: overall response rate (ORR).3
  • Key secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival, safety, pharmacokinetics, patient reported outcomes, and minimal residual disease.3
  • Dosing
    • Step-up doses (SUDs) of TALVEY were administered as follows3:
      • 0.4 mg/kg SC QW: 0.01 mg/kg, and 0.06 mg/kg.
      • 0.8 mg/kg SC Q2W: 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg. 
    • Subsequent treatment doses: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W until disease progression, unacceptable toxic effects, withdrawal of consent, or end of study.3
  • Premedications: glucocorticoid (dexamethasone 16 mg or equivalent), antihistamine, and antipyretic were required to be administered for each SUD, 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 each SUD and the first full treatment dose of TALVEY.3

Chari et al (2025)3,4 published a post hoc analysis with a longer-term follow-up to evaluate the efficacy and safety of TALVEY at RP2D at a median follow-up of 25.6 months (IQR, 8.5-25.9) for the 0.4 mg/kg SC QW cohort, 19.4 months (IQR, 9.2-20.7) for the 0.8 mg/kg SC Q2W cohort, and 16.8 months (IQR, 7.6-18.7) for the prior TCR-exposed cohort from phases 1 and 2 of the MonumenTAL-1 study.

Results

Patient Characteristics


MonumenTAL-1 Study: Baseline Characteristics3
Characteristic
0.4 mg/kg SC QWa
(N=143)
0.8 mg/kg SC Q2Wa
(N=154)
Prior TCRa,b
(N=78)
Median age, years (IQR)
67 (58-72)
67 (58-74)
61 (55-68)
Sex, n (%)
   Female
65 (45)
64 (42)
29 (37)
   Male
78 (55)
90 (58)
49 (63)
Race, n (%)
   White
128 (90)
126 (82)
71 (91)
   Black
12 (8)
17 (11)
3 (4)
   Asian
1 (1)
6 (4)
4 (5)
   Native Hawaiian or other Pacific
   islander
0
1 (1)
0
   Multiple
0
1 (1)
0
   Unknown
0
1 (1)
0
   Not reported
2 (1)
2 (1)
0
Bone marrow plasma cells ≥60%, n (%)c
17 (12)
34 (23)
11 (15)
Extramedullary plasmacytomas ≥1, n (%)d
33 (23)
41 (27)
25 (32)
High-risk cytogenetics, n (%)e
41 (31)
40 (30)
25 (37)
ISS stage, n (%)
   I
62 (43)
68 (44)f
38 (49)
   II
53 (37)
48 (31)f
27 (35)
   III
28 (20)
37 (24)f
13 (17)
ECOG performance score, n (%)
   0
44 (31)
58 (38)
36 (46)
   1
86 (60)
84 (55)
39 (50)
   2
13 (9)
12 (8)
3 (4)
Median time since diagnosis, years (IQR)
6.7 (4.3-9.7)
6.3 (3.8-10.4)
6.3 (4.2-9.9)
Previous lines of therapy, n (IQR)
5 (4.0-6.0)
4.5 (4.0-6.0)
6 (5.0-8.0)
Previous stem cell transplantation, n (%)
113 (79)
121 (79)
69 (88)
Exposure status, n (%)
   Triple-classg
143 (100)
154 (100)
78 (100)
   Penta-drugh
105 (73)
107 (69)
65 (83)
   Belantamab mafodotin
22 (15)
17 (11)
11 (14)
   BsAb
-
-
26 (33)
   CAR-T
-
-
57 (73)
   BsAb + CAR-T
-
-
5 (6)
Refractory status, n (%)
PIi
116 (81)
129 (84)
71 (91)
   Immunomodulatory drug
134 (94)
141 (92)
76 (97)
      Thalidomide
12 (8)
20 (13)
6 (8)
      Lenalidomide
115 (80)
110 (71)
69 (88)
      Pomalidomide
110 (77)  
106 (69)
60 (77)
   Anti-CD38 mAbj
134 (94)
142 (92)
74 (95)
   Triple-classg
107 (75)
110 (71)
66 (85)
   Penta-drugh
45 (31)
39 (25)
34 (44)
   Belantamab mafodotin
18 (13)
14 (9)
8 (10)
   To last line of therapy
134 (94)
145 (94)
45 (58)
Abbreviations: BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T-cell therapy; ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; IQR, interquartile range; mAb, monoclonal antibody; MAGE-A1, melanoma antigen gene family member A1; PI, proteasome inhibitor; Q2W, every other week; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy.
aReceived 2-3 SUDs.
bPrior TCR-therapy was primarily targeting BCMA (96%; n=75); other targets included CD38 (n=2) and MAGE-A1 (n=1).
cMaximum value was selected when results from both the bone marrow biopsy and bone marrow aspirate were available. Evaluated in 138, 150, and 73 patients in the 0.4 mg/kg SC QW, 0.8 mg/kg SC Q2W, and prior TCR cohorts, respectively.
dSoft tissue plasmacytomas not associated with the bone were included.
edel(17p), t(4;14), or t(14;16). Evaluated in 132, 133, and 67 patients in the 0.4 mg/kg SC QW, 0.8 mg/kg SC Q2W, and prior TCR cohorts, respectively.
fEvaluated in 153 patients.
g≥1 PI, ≥1 immunomodulatory drug, and ≥1 anti-CD38 mAb.
h≥2 PIs, ≥2 immunomodulatory drugs, and ≥1 anti-CD38 mAb.
iBortezomib, carfilzomib, or ixazomib.
jDaratumumab, isatuximab, or an investigational anti-CD38 mAb.

Efficacy

  • ORR was 74%, 69%, and 67% in the 0.4 mg/kg SC QW, 0.8 mg/kg SC Q2W, and prior TCR-exposed cohorts, respectively. See Table: MonumenTAL-1 Study: Efficacy Outcomes for additional details.

MonumenTAL-1 Study: Efficacy Outcomes3
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 (range)
25.6 (8.5-25.9)
19.4 (9.2-20.7)
16.8 (7.6-18.7)
ORR, % (95% CI)
74 (66-81)
69 (62-77)
67 (55-77)
   sCR, %
23
30
32
   CR, %
10
10
9
   VGPR, %
27
19
14
   PR, %
15
10
12
≥VGPR, %
59
59
55
Median time to first response, months (IQR)
1.2 (1.1-1.6)
1.3 (1.2-1.7)
1.2 (1.1-1.7)
Median time to ≥VGPR, months (IQR)a
1.9 (1.2-3.0)
2.2 (1.2-4.0)
1.4 (1.1-2.7)
Median DOR, months (95% CI)b
9.5 (6.7-13.4)
16.9 (12.9-NE)
-
   12-month DOR rate, % (95% CI)
-
-
56 (41-69)
Median PFS, months (95% CI)c
7.5 (5.7-9.4)
11.2 (8.4-16.9)
7.7 (4.1-14.5)
12-month OS rate, % (95% CI)d
76 (68-83)
77 (69-83)
74 (62-82)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; IQR, interquartile range; NE, not estimable; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; Q2W, 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 October 11, 2023.
aAs per post hoc analysis.
bA total of 74 events in 106 responders and 48 events in 107 responders were reported in the 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W cohorts, respectively.
cA total of 107 events in 143 patients, 89 events in 154 patients, and 47 events in 78 patients were reported in the 0.4 mg/kg SC QW, 0.8 mg/kg SC Q2W, and prior TCR cohorts, respectively.
dA total of 58 events in 143 patients, 44 events in 154 patients, and 27 events in 78 patients were reported in the 0.4 mg/kg SC QW, 0.8 mg/kg SC Q2W, and prior TCR cohorts, respectively. Medians are not available since the data are immature.

Safety

  • The incidence of hematologic adverse events (AEs) is outlined in Table: MonumenTAL-1 Study: Hematologic AEs.
  • The incidence of nonhematologic AEs is outlined in Table: MonumenTAL-1 Study: Nonhematologic AEs.
  • Patients who developed on-target, off-tumor AEs in early treatment cycles had a greater likelihood of experiencing response vs those who did not.
  • Overall, 55% of patients (n=78) in the 0.4 mg/kg SC QW cohort, 53% of patients (n=81) in the 0.8 mg/kg SC Q2W cohort, and 51% of patients (n=40) in the prior TCR-exposed cohort experienced at least 1 serious AE.
  • Weight loss occurred early, but stabilized and increased slightly over time, even in patients with oral AEs.
  • AEs leading to treatment discontinuation and dose modifications are presented in Table: MonumenTAL-1 Study: AEs Leading to Treatment Discontinuation and Dose Modification.
  • Fatal AEs were reported in 5 patients in the 0.4 mg/kg SC QW cohort, 7 patients in the 0.8 mg/kg SC Q2W cohort, and no patients in the prior TCR-exposed cohort.
  • Three patients (0.4 mg/kg SC QW cohort, n=2; 0.8 mg/kg SC Q2W cohort, n=1) were in response at the time of death. No treatment-related deaths were reported.
Skin-, Nail-, Rash- and Taste-Related AEs
Cytokine Release Syndrome
  • CRS events primarily occurred during administration of SUDs and first full doses, with few events occurring at or after treatment cycle 2. See Table: MonumenTAL-1 Study: CRS for additional details.
Neurotoxic AEs
  • One patient in the 0.8 mg/kg SC Q2W cohort had grade 2 cerebellar toxicity (reported as ataxia), which led to treatment discontinuation.
  • For details regarding ICANS, see Table: MonumenTAL-1 Study: ICANS.
Infections
  • Details on infections are presented in the Table: MonumenTAL-1 Study: Infections.
  • The polyclonal immunoglobulin G (IgG) level/titer transiently dropped for the first 2 to 3 months of therapy but gradually increased above the baseline value as patients continued TALVEY therapy. IgG patterns were similar between responders and nonresponders.
  • In the 0.4 mg/kg QW, 0.8 mg/kg Q2W, and previous TCR cohorts, intravenous immunoglobulin (IVIG; before TALVEY or for posttreatment hypogammaglobulinemia) was administered to 8% (n=12), 9% (n=14), and 19% (n=15) of patients, respectively.
  • A total of 5 patients died due to infections (0.4 mg/kg SC QW cohort, n=3; 0.8 mg/kg SC Q2W cohort, n=2). Coronavirus disease 2019 (COVID-19) pneumonia led to death in 2 patients (0.4 mg/kg SC QW, n=1; 0.8 mg/kg SC Q2W cohort, n=1).

MonumenTAL-1 Study: Hematologic AEs3,4
Event, n (%)
0.4 mg/kg SC QWa,b
(N=143)
0.8 mg/kg SC Q2Wa,b
(N=154)
Prior TCRa,c
(N=78)
Grade 1/2
Grade 3
Grade 4
Grade 1/2
Grade 3
Grade 4
Grade 1/2
Grade 3
Grade 4
Grade 5
Neutropenia
6 (4)
29 (20)
15 (10)
11 (7)
24 (16)
9 (6)
3 (4)
18 (23)
19 (24)
0
Anemia
19 (13)
45 (31)
0
26 (17)
40 (26)
0
17 (22)
21 (27)
0
0
Thrombocytopenia
10 (7)
15 (10)
14 (10)
17 (11)
14 (9)
14 (9)
9 (12)
11 (14)
10 (13)
0
Leukopenia
12 (8)
6 (4)
5 (3)
11 (7)
14 (9)
4 (3)
3 (4)
8 (10)
6 (8)
0
Lymphopenia
3 (2)
17 (12)
20 (14)
6 (4)
14 (9)
26 (17)
2 (3)
4 (5)
9 (12)
0
Febrile neutropenia
-
-
-
-
-
-
0
4 (5)
0
0
Abbreviations: AE, adverse event; Q2W, every other week; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy.
Clinical data cutoff date of October 11, 2023.
aReceived 2-3 SUDs.
bAEs are listed by frequency on an any-grade basis. AEs listed are grade 1-2 events occurring in at least 20% of patients in either group or grade 3 or worse occurring in at least 10% of patients in either group.
cAEs are listed by frequency on an any-grade basis and include those occurring in ≥10% of patients or grade ≥3 AEs occurring in ≥5%.

MonumenTAL-1 Study: Nonhematologic AEs3,4
Event, n (%)
0.4 mg/kg SC QWa,b
(N=143)
0.8 mg/kg SC Q2Wa,b
(N=154)
Prior TCRa,c
(N=78)
Grade 1/2
Grade 3
Grade 4
Grade 1/2
Grade 3
Grade 4
Grade 1/2
Grade 3
Grade 4
Grade 5
Taste-related changesd
103 (72)
-
-
110 (71)
-
-
59 (76)
-
-
-
CRS
110 (77)
3 (2)
0
114 (74)
1 (1)
0
56 (72)
1 (1)
0
0
Non-rash skin-related AEse
81 (57)
0
0
113 73)
1 (1)
0
49 (63)
0
0
0
Nail-related AEsf
79(55)
0
0
82 (53)
0
0
45 (58)
0
0
0
Dry mouth
38 (27)
0
0
60 (39)
0
0
34 (44)
0
0
0
Weight decreased
56 (39)
3 (2)
0
56 (36)
8 (5)
0
28 (36)
1 (1)
0
0
Fatigue
30 (21)
5 (3)
0
41 (27)
1 (1)
0
24 (31)
1 (1)
0
0
Pyrexia
52 (36)
4 (3)
0
40 (26)
2 (1)
-
25 (32)
0
0
0
Rash-related AEsg
57 (40)
2 (1)
0
45 (29)
8 (5)
0
23 (29)
2 (3)
0
0
Cough
28 (20)
0
0
32 (21)
0
0
21 (27)
0
0
0
Arthralgia
28 (20)
2 (1)
0
27 (18)
0
0
18 (23)
0
0
0
Decreased appetite
27 (19)
2 (1)
0
41 (27)
2 (1)
0
17 (22)
1 (1)
0
0
Dysphagia
34 (24)
0
0
35 (23)
3 (2)
0
18 (23)
0
0
0
Constipation
25 (17)
0
0
31 (20)
0
0
17 (22)
0
0
0
Diarrhea
34 (24)
3 (2)
0
40 (26)
2 (1)
0
16 (21)
0
0
0
Pain in extremity
-
-
-
-
-
-
16 (21)
0
0
0
Dyspnea
-
-
-
-
-
-
13 (17)
1 (1)
0
0
Nausea
29 (20)
0
0
30 (19)
0
0
14 (18)
0
0
0
Headache
26 (18)
1 (1)
0
31 (20)
1 (1)
0
13 (17)
0
0
0
Stomatitis
-
-
-
-
-
-
13 (17)
0
0
0
URTI
-
-
-
-
-
-
13 (17)
0
0
0
Hypophosphatemia
-
-
-
-
-
-
10 (13)
2 (3)
0
0
ALT increased
-
-
-
-
-
-
8 (10)
3 (4)
0
0
COVID-19
14 (10)
2 (1)
0
35 (23)
4 (3)
0
10 (13)
1 (1)
0
0
Asthenia
36 (25)
3 (2)
0
16 (10)
2 (1)
0
9 (12)
1 (1)
0
0
Injection-site erythema
-
-
-
-
-
-
10 (13)
0
0
0
Oropharyngeal pain
-
-
-
-
-
-
10 (13)
0
0
0
Chills
-
-
-
-
-
-
9 (12)
0
0
0
Back pain
-
-
-
-
-
-
9 (12)
0
0
0
Hypokalemia
-
-
-
-
-
-
9 (12)
0
0
0
Hypotension
-
-
-
-
-
-
9 (12)
0
0
0
Hypertension
-
-
-
-
-
-
3 (4)
4 (5)
0
0
Abbreviations: ALT, alanine aminotransferase; AE, adverse event; COVID-19, coronavirus disease 2019; CRS, cytokine release syndrome; Q2W, every other week; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy; URTI, upper respiratory tract infection.
Clinical data cutoff date of October 11, 2023.
aReceived 2-3 SUDs.
bAEs are listed by frequency on an any-grade basis. AEs listed are grade 1-2 events occurring in at least 20% of patients in either group or grade 3 or worse occurring in at least 10% of patients in either group.
cAEs included are grade 1/2 events occurring in ≥10% of patients or grade ≥3 AEs occurring in ≥5%. AEs are listed by frequency on an any-grade basis.
dIncludes dysgeusia, ageusia, hypogeusia, and taste disorder. Per Common Terminology Criteria for Adverse Events, the maximum grade for these events was 2.
eIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
fIncludes nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging.
gIncludes rash, maculopapular rash, erythematous rash, and erythema.

MonumenTAL-1 Study: AEs Leading to Treatment Discontinuation and Dose Modification3,4
Event, n (%)
0.4 mg/kg SC QWa (N=143)
0.8 mg/kg SC Q2Wa (N=154)
Prior TCRa
(N=78)
Treatment discontinuation
7 (5)
14 (9)
4 (5)
   Dysgeusia
0
2 (1)
0
   ICANS
2 (2)b
1 (1)b
0
   Ataxia
0
1 (1)
0
   Skin-related disordersc
2 (1)
2 (1)
0
   Nail-related AEs
0
0
0
   Rash-related AEs
0
0
0
   Taste change
0
2 (-)
0
   Administration site conditionsd
2 (1)
2 (1)
0
   Infectionse
2 (1)
0
1 (1)
   Cardiac disordersf
0
2 (1)
0
   Weight decreased
1 (1)
2 (1)
1 (1)
   GI disordersg
2 (1)
0
0
   CRS
0
1 (1)
0
   Graft vs host disease
0
0
1 (1)
   Hypercalcemia
0
1 (1)
0
   AML
0
1 (1)
0
   Myelodysplastic syndrome
0
0
1 (1)
   Renal failure
0
1 (1)
0
Dose reduction
22 (15)
13 (8)
9 (12)
   Taste disorderh
10 (7)
5 (3)
4 (5)
   Weight decreased
7 (5)
4 (3)
2 (3)
   Decreased appetite
2 (1)
1 (1)
1 (1)
   Dry mouth/dysphagia
1 (1)
4 (3)
4 (5)
   Other GI disorderi
2 (1)
1 (1)
0
   Parosmia
1 (1)
0
0
   Skin and rash disordersj
7 (5)
3 (2)
4 (5)
   Nail disorderk
2 (1)
1 (1)
1 (1)
   General disorders and
   administration site conditionsl
4 (3)
0
2 (3)
   CRS
1 (1)
1 (1)
0
   ICANS
1 (1)b
0
0
   Malnutrition
1 (1)
0
0
   CMV infection
0
1 (1)
0
   Myalgia
0
0
1 (1)
   Sinusitis
0
0
1 (1)
   Multisystem inflammatory
   syndrome
0
0
1 (1)
Abbreviations: AE, adverse event; AML, acute myeloid leukemia; CMV, cytomegalovirus; CRS, cytokine release syndrome; GI, gastrointestinal; ICANS, immune effector cell-associated neurotoxicity syndrome; Q2W, every other week; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy.
Clinical data cutoff date of October 11, 2023.
aReceived 2-3 SUDs.
bAssessed only in phase 2, with percentage calculated based on n=122 for the 0.4 mg/kg SC QW cohort and n=118 for the 0.8 mg/kg SC Q2W cohort.
cIncludes skin exfoliation, dry skin, and generalized exfoliative dermatitis.
dIncludes asthenia, general physical health deterioration, and mucosal inflammation.
eIncludes fungal sepsis, pneumonia, and rash pustular.
fIncludes cardiac arrest and sinus bradycardia.
gIncludes colitis and oral AEs.
hIncludes dysgeusia, ageusia, and taste disorder.
iIncludes glossitis, nausea, and oral AEs.
jIncludes dry skin, palmar-plantar erythrodysesthesia syndrome, maculopapular rash, hyperkeratosis, mucocutaneous toxicity, pruritus, rash, skin exfoliation, skin ulcer, and skin fissures.
kIncludes nail disorder, nail hypertrophy, nail onycholysis, and nail onychomadesis.
lIncludes asthenia, chills, fatigue, and malaise.

MonumenTAL-1 Study: Duration and Outcomes of Skin-, Nail-, Rash-, and Taste-Related AEs4
Event
0.4 mg/kg SC QWa (N=143)
0.8 mg/kg SC Q2Wa (N=154)
Prior TCRa
(N=78)
Non-rash skin-related AEsb
   Total, n (%)
81 (57)
113 (73)
49 (63)
   Leading to dose modification,
   n (%)
12 (8)
2 (1)
4 (5)
   Median duration, days (IQR)
37.5 (20.5-74.5)
40.0 (16.0-98.0)
31.0 (20.0-57.0)
   Outcome, n (%)
      Number of events
157 (-)
195 (-)
99 (-)
         Recovered or resolved
95 (61)
112 (57)
66 (67)
         Not recovered or not
         resolved
58 (37)
76 (39)
33 (33)
         Recovered or resolved
         with sequelae
1 (1)
0
0
         Recovering or resolving
1 (1)
1 (1)
0
         Unknown
0
0
0
      Missing
2 (1)
6 (3)
0
Nail-related AEsc
   Total, n (%)
79 (55)
82 (53)
45 (58)
   Leading to dose modification,
   n (%)
1 (1)
1 (1)
2 (3)
   Median duration, days (IQR)
106.0 (61.0-190.0)
99.0 (59.0-203.0)
83.0 (18.5-151.5)
   Outcome, n (%)
      Number of events
100
105
57
         Recovered or resolved
36 (36)
33 (31)
20 (35)
         Not recovered or not
         resolved
63 (63)
67 (64)
34 (60)
         Recovered or resolved
         with sequelae
0
0
0
         Recovering or resolving
0
0
0
         Unknown
1 (1)
0
1 (2)
         Missing
0
5 (5)
2 (4)
Rash-related AEsd
   Total, n (%)
57 (40)
45 (29)
25 (32)
   Leading to dose modification,
   n (%)
9 (6)
6 (4)
2 (3)
   Median duration, days (IQR)
27.5 (11.5-50.5)
28.5 (13.0-57.0)
14.0 (7.0-28.0)
   Outcome, n (%)
      Number of events
75
68
42
         Recovered or resolved
67 (89)
52 (76)
31 (74)
         Not recovered or not
         resolved
7 (9)
15 (22)
11 (26)
         Recovered or resolved
         with sequelae
0
0
0
         Recovering or resolving
1 (1)
1 (1)
0
         Unknown
0
0
0
         Missing
0
0
0
Taste-related AEse
   Total, n (%)
103 (72)
110 (71)
59 (76)
   Leading to dose modification,
   n (%)
12 (8)
9 (6)
6 (8)
   Median duration, days (IQR)
119.5 (51.0-232.0)
168.5 (84.0-325.0)
132.0 (37.0-303.0)
   Outcome, n (%)
      Number of events
127
126
68
         Recovered or resolved
65 (51)
50 (40)
26 (38)
         Not recovered or not
         resolved
59 (46)
67 (53)
40 (59)
         Recovered or resolved
         with sequelae
0
0
0
         Recovering or resolving
2 (2)
1 (1)
0
         Unknown
1 (1)
0
0
         Missing
0
8 (6)
2 (3)
Abbreviations: AE, adverse event; IQR, interquartile range; Q2W, every other week; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy.
Clinical data cutoff date of October 11, 2023.
aReceived 2-3 SUDs.
bIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
cIncludes nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging.
dIncludes rash, maculopapular rash, erythematous rash, and erythema.
eIncludes dysgeusia, ageusia, hypogeusia, and taste disorder.

MonumenTAL-1 Study: CRS4
Event
0.4 mg/kg
SC QWa
(N=143)
0.8 mg/kg
SC Q2Wa
(N=154)
Prior TCRa
(N=78)
Patients with CRS, n (%)
113 (79)
115 (75)
57 (73)
   Grade 1
89 (62)
88 (57)
39 (50)
   Grade 2
21 (15)
26 (17)
17 (22)
   Grade 3
3 (2)
1 (1)
1 (1)
CRS symptoms (>10% in any cohort), n (%)
   Pyrexia
113 (79)
114 (74)
56 (72)
   Hypotension
19 (13)
20 (13)
15 (19)
   Chills
13 (9)
21 (14)
11 (14)
   Hypoxia
11 (8)
9 (6)
8 (10)
Median time to onset, hours (IQR)b
25.9 (17.8-31.9)
27.8 (21.0-34.6)
27.4 (21.2-34.5)
Median duration, hours (IQR)c
14.5 (4.0-32.0)
17.0 (5.6-33.8)
20.6 (6.6-31.5)
Patients with CRS up to first full dose, n (%)
   SUD 1
48 (34)
41 (27)
23 (29)
   SUD 2
70 (49)
63 (41)
34 (44)
   SUD 3
-
55 (36)
1 (1)
   First full dose
38 (27)
22 (14)
22 (28)
Patients with CRS cycle 2+, n (%)
5 (3)
5 (3)
2 (3)
Patients receiving supportive measures, n (%)d
106 (74)
109 (71)
54 (69)
   Acetaminophen
80 (56)
81 (53)
42 (54)
   Tocilizumabe
50 (35)
57 (37)
37 (47)
   Corticosteroids
5 (3)
6 (4)
11 (14)
   Oxygen
8 (6)
10 (6)
7 (9)
      Nasal cannula low flow
      (≤6 L/min)
8 (6)
9 (6)
6 (8)
      Face mask
0
0
1 (1)
      Venturi mask
1 (1)
0
0
      Other
0
1 (1)
0
   Vasopressorf
2 (1)
1 (1)
1 (1)
Patients with >1 CRS event, n (%)
46 (32)
51 (33)
23 (29)
   Grade worsened at subsequent
   event
6 (4)
7 (5)
3 (4)
Abbreviations: CRS, cytokine release syndrome; IQR, interquartile range; Q2W, every other week; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy.
Clinical data cutoff date of October 11, 2023.
aReceived 2-3 SUDs.
bRelative to the most recent dose.
cCRS with both start and end dates available.
dPatients could receive more than 1 supportive therapy.
eTocilizumab was advised for grade 2 and higher but allowed for grade 1; the protocol did not recommend prophylactic tocilizumab use.
fOnly single vasopressor used.

MonumenTAL-1 Study: ICANS4
Event
0.4 mg/kg
SC QWa,b
(N=122)
0.8 mg/kg
SC Q2Wa,b
(N=118)
Prior TCRa,b
(N=61)
Patients with ICANS, n (%)
13 (11)
12 (10)
2 (3)
   Grade 1
4 (3)
4 (3)
2 (3)
   Grade 2
7 (6)
4 (3)
0
   Grade 3
2 (2)
3 (3)
0
   Grade 4
0
1 (1)
0
ICANS symptoms (≥2% in any cohort), n (%)
   Confusional state
6 (5)
5 (4)
0
   Disorientation
3 (2)
2 (2)
0
   Somnolence
3 (2)
2 (2)
0
   Depressed level of
   consciousness
3 (2)
1 (1)
0
Median time to onset, hours (IQR)c
23.6 (15.0-53.7)
31.9 (14.7-52.0)
81.6 (47.6-115.5)
Median duration, hours (IQR)
15.5 (2.7-23.9)
7.8 (3.5-24.9)
25.3 (2.0-48.5)
Number of ICANS events, n (%)
21 (-)
15 (-)
2 (-)
   Recovered or resolved
18 (86)
12 (80)
2 (100)
   Not recovered or not resolved
2 (10)
2 (13)
0
   Recovering or resolving
1 (5)
0
0
   Unknown
0
1 (7)
0
Concurrent CRS, n (%)d
   Yes
14 (67)
10 (67)
2 (100)
   No
7 (33)
5 (33)
0
Abbreviations: CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; IQR, interquartile range; Q2W, every other week; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy.
Clinical data cutoff date of October 11, 2023.
aReceived 2-3 SUDs.
bICANS was only measured in phase 2.
cRelative to the most recent dose.
dConcurrent CRS includes ICANS events that occur simultaneously with CRS or within 7 days after its resolution.

MonumenTAL-1 Study: Infections3,4
Event, n (%)
0.4 mg/kg SC QWa (N=143)
0.8 mg/kg SC Q2Wa
(N=154)
Prior TCRa (N=78)
Any infection
85 (59)
105 (68)
59 (76)
Grade 3-4 infections
29 (20)
28 (18)
20 (26)
Opportunistic infectionsb
5 (3)
9 (6)
3 (4)
COVID-19 cases
16 (11)
39 (25)
11 (14)
Abbreviations: COVID-19, coronavirus disease 2019; IVIG, intravenous immunoglobulin; Q2W, every other week; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy.
Clinical data cutoff date of October 11, 2023.
aReceived 2-3 SUDs.
bIncludes esophageal candidiasis, adenovirus infection, herpesvirus 6 infection, ophthalmic herpes, varicella zoster virus infection, cytomegalovirus infection, fungal sepsis, and viral retinitis.

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-exposed cohort. Rasche et al (2024)5 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-exposed 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 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-exposed 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-exposed cohorts were similar, except for a higher proportion of African American patients (9%; [n/N=32/375]).5

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 Outcomes5
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; USPI, United States Prescribing Information; 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.
bEvaluated in 106, 107, and 52 patients in the 0.4 mg/kg SC QW, 0.8 mg/kg SC Q2W, and prior TCR cohorts, respectively.
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 Cohort5

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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 Subgroups5
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 Population5
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 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-exposed 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-exposed 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-exposed cohorts, respectively.
  • No treatment-related deaths were reported.

MonumenTAL-1 Study: GPRC5D-Associated AEs5
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.
aIncludes ageusia, dysgeusia, hypogeusia, and taste disorder.
bIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
cIncludes nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging.
dIncludes rash, maculo-papular rash, erythematous rash, and erythema.
eIncludes 1 (0.6%) grade 3/4 events.
fIncludes 2 (1.4%) grade 3/4 events.
gIncludes 8 (5.2%) grade 3/4 events.
hIncludes 2 (2.6%) grade 3/4 events.

MonumenTAL-1 Study: Weight Loss in Patients With Oral Toxicitya in the QW and Q2W Cohorts5

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; SUD, step-up dose; SE, standard error.
Clinical data cutoff date of January 29, 2024.
aIncludes 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.

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

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-exposed 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-exposed 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 07 April 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 Chari A, Touzeau C, Schinke C, et al. Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1-2 study. Lancet Haematol. 2025;In Press.  
4 Chari A, Touzeau C, Schinke C, et al. Supplement to: Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1-2 study. Lancet Haematol. 2025;In Press.  
5 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.  
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 Chari A, Minnema MC, Berdeja JG. Protocol to: Talquetamab, a T-cell–redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. 2022;387(24):2232-2244.  
8 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 April 07]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03399799 NLM Identifier: NCT03399799.  
9 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 April 07]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04634552 NLM Identifier: NCT04634552.  
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