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TALVEY® (talquetamab-tgvs)

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TALVEY - MonumenTAL-2 (MMY1004) Study Cohort E

Last Updated: 07/08/2024

SUMMARY

  • Janssen does not recommend any practices, procedures or usage that deviate from approved labeling.
  • MonumenTAL-2 (MMY1004) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with multiple myeloma (MM). Cohort E is evaluating the safety and efficacy of TALVEY in combination with pomalidomide in 35 patients with relapsed or refractory multiple myeloma (RRMM).1-3
    • Searle et al (2024)3 presented the updated safety and efficacy results of TALVEY in combination with pomalidomide from the MonumenTAL-2 study. Following step-up dosing, patients received TALVEY + pomalidomide daily at a median follow-up of 16.8 months (range, 1.2-25.1).
    • Matous et al (2023)1 presented the initial efficacy and safety results of TALVEY in combination with pomalidomide from the MonumenTAL-2 study. Following step-up dosing, patients received TALVEY 0.4 mg/kg once every week (QW) + pomalidomide daily at a median follow-up of 15.0 months (range, 1.2-19.0) or TALVEY 0.8 mg/kg once every other week (Q2W) + pomalidomide daily at a median follow-up of 11.1 months (range, 1.2-14.8).

CLINICAL DATA - Monumental-2 study (Cohort e) - phase 1b

MonumenTAL-2 (MMY1004; clinicaltrials.gov identifier NCT05050097) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination other anticancer therapies in patients with MM.1-3

Cohort E of the MonumenTAL-2 study is evaluating the efficacy and safety of TALVEY in combination with pomalidomide in 35 patients with RRMM.1-3

Study Design/Methods

MonumenTAL-2 (Cohort E): Study Design1,3

A blue and white chart with white text Description automatically generated

Abbreviations: AE, adverse event; ASTCT, American Society for Transplantation and Cellular Therapy; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T cell; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; GPRC5D, G protein-coupled receptor, class C, group 5, member D; ICANS, immune effector cell-associated neurotoxicity syndrome; IMWG, International Myeloma Working Group; MM, multiple myeloma; ORR, overall response rate; PFS, progression-free survival; PI, proteasome inhibitor; PO, by mouth; Q2W, every other week; QW, weekly, SC, subcutaneous.
aAEs assessed per CTCAE v5.0, except for CRS and ICANS, which were graded per ASTCT guidelines.
bAssessed per IMWG 2016 criteria.

Searle et al (2024)3 presented the updated safety and efficacy results of TALVEY in combination with pomalidomide from the MonumenTAL-2 study at a median follow-up of 16.8 months (range, 1.2-25.1), which are summarized below.

Results

Patient Characteristics

  • Patient characteristics are presented in Table: MonumenTAL-2 (Cohort E): Patient Characteristics.
  • Overall, the median age was 65.0 years. High-risk cytogenetics were noted in 39.1% of patients and 14.3% of patients had extramedullary disease.
  • Prior treatments included the following: chimeric antigen receptor T cell (CAR-T, 8.6%), bispecific antibody (2.9%), anti-CD38 antibody (74.3%) and pomalidomide (22.9%).

Efficacy


MonumenTAL-2 (Cohort E): Updated Efficacy Outcomes3
Parameter
TALVEY + Pomalidomide
(N=35)
Median follow-up, months (range)
16.8 (1.2-25.1)
ORR, n (%)
31 (88.6)
   sCR, %
40.0
   CR, %
11.4
   VGPR, %
28.6
   PR, %
8.6
≥CR, %
51.4
Median time to first response, months (range)
1.1 (0.0-3.3)
Median PFS, months (95% CI)
NR (12.9-NE)
   12-month PFS rate, % (95% CI)
72.6 (53.9-84.7)
Median DOR, months (95% CI)
NR (12.0-NE)
   12-month DOR rate, % (95% CI)
74.4 (53.5-86.9)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; NE, not estimable; NR, not reached; ORR, overall response rate; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cut-off date of April 22, 2024.

MonumenTAL-2 (Cohort E): DOR by Depth of Best Response3
DOR by depth of response
12-month DOR rate, % (95% CI)
PR
0.0 (NE-NE)
n=2
VGPR
78.8 (38.1-94.3)
n=11
CR
80.4 (50.6-93.2)
n=17
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; NE, not estimable; PR, partial response; VGPR, very good partial response.
Clinical data cut-off date of April 22, 2024.

Safety

  • Treatment-emergent adverse events (TEAEs) in ≥25% of patients reported at a data cutoff date of April 22, 2024, are summarized in Table: MonumenTAL-2 (Cohort E): Updated TEAEs (≥25%).
  • The most common infections (mostly grade 1/2) were pneumonia, upper respiratory tract infections, and COVID-19.
    • First-onset infections generally occurred in the first few cycles of treatment.
  • In patients with or without oral toxicities, weight loss was evident early but stabilized and improved over time, with a gradual improvement noted in patients with oral toxicities.
  • Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 patients; all events were grade 1 in severity.
  • Overall, 37.1% and 48.6% of patients had a reduction in TALVEY and pomalidomide doses, respectively, due to AEs. A total of 65.7% and 77.1% of patients skipped TALVEY and pomalidomide doses, respectively, due to AEs.
    • The most common AEs leading to pomalidomide dose reduction included neutropenia, peripheral neuropathy, and fatigue.
    • AEs were managed by reducing doses and changing dosing schedules.
  • Nine patients had AEs that led to treatment discontinuation. Few treatment discontinuations due to taste-, skin-, nail-, and rash-related AEs were reported.

MonumenTAL-2 (Cohort E): Updated TEAEs (≥25%)3
Event, n (%)
All Patients (N=35)
Any Grade
Grade 3/4
Hematologic AEsa
   Neutropenia
22 (62.9)
20 (57.1)
   Anemia
13 (37.1)
9 (25.7)
   Thrombocytopenia
10 (28.6)
7 (20.0)
Nonhematologic AEs
   Taste-relatedb
30 (85.7)
0
   Infections
28 (80.0)
8 (22.9)
   CRS
26 (74.3)
1 (2.9)
   Skin-relatedc
26 (74.3)
2 (5.7)
   Nail-relatedd
24 (68.6)
0
   Dry mouth
19 (54.3)
0
   Fatigue
19 (54.3)
5 (14.3)
   Pyrexia
14 (40.0)
1 (2.9)
   Nausea
13 (37.1)
0
   Diarrhea
11 (31.4)
0
   Headache
10 (28.6)
1 (2.9)
   Rash-relatede
10 (28.6)
1 (2.9)
   Back pain
9 (25.7)
1 (2.9)
   Cough
9 (25.7)
0
   Weight decreased
9 (25.7)
2 (5.7)
Abbreviations: AE, adverse event; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; TEAE, treatment-emergent adverse event.
Clinical data cut-off date of April 22, 2024.
aCytopenias were mostly of grade 3/4 in severity and limited to the first few cycles.
bIncludes dysgeusia, ageusia, taste disorder, and hypogeusia. Per CTCAE v5.0, the maximum grade of dysgeusia is 2.
cIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
dIncludes nail discoloration, nail disorder, nail toxicity, nail dystrophy, nail ridging, onychoclasis, onycholysis, and onychomadesis.
eIncludes rash, rash maculopapular, rash erythematous, and erythema.

Pharmacokinetics

  • There was no reduction in total cluster of differentiation 19 (CD19+) B cells observed during treatment, which was consistent with the target expression.

Matous et al (2023)1 presented the initial efficacy and safety results of TALVEY in combination with pomalidomide from the MonumenTAL-2 study at a median follow-up of 15.0 months (range, 1.2-19.0) for TALVEY 0.4 mg/kg QW + pomalidomide cohort and at a median follow-up of 11.1 months (range, 1.2-14.8) for TALVEY 0.8 mg/kg Q2W + pomalidomide cohort. Results are summarized below.

Results

Patient Characteristics


MonumenTAL-2 (Cohort E): Patient Characteristics1
Characteristic
TALVEY 0.4 mg/kg QW + Pomalidomide
(n=16)
TALVEY 0.8 mg/kg Q2W + Pomalidomide
(n=19)
Median age (range), years
69.5 (49-78)
 63.0 (43-76)
Male, n (%)
7 (43.8)
14 (73.7)
Race, n (%)
   White
12 (75.0)
16 (84.2)
   African American/Black
1 (6.3)
2 (10.5)
   Unknown/not reported
3 (18.8)
1 (5.3)
Extramedullary plasmacytomas ≥1a, n (%)
2 (12.5)
3 (15.8)
High-risk cytogeneticsb, n (%)
5 (31.3)
4 (21.1)
ISS stage, n (%)
   I
6 (37.5)
6 (31.6)
   II
8 (50.0)
10 (52.5)
   III
2 (12.5)
3 (15.8)
Time since diagnosis, median (range), months
71.8 (16.9-153.9)
49.7 (18.7-166.8)
Median prior lines of therapy (range)
3 (2-12)
3 (2-5)
Exposure status, n (%)
   Triple-class
12 (75.0)
14 (73.7)
   Penta-drug
5 (31.3)
3 (15.8)
   Anti-BCMA BsAb
1 (6.3)
0
   Anti-BCMA CAR-T therapy
3 (18.8)
0
   Pomalidomide
5 (31.3)
3 (15.8)
   Anti-CD38 antibody
12 (75.0)
14 (73.7)
Refractory status, n (%)
   Triple-class
5 (31.1)
4 (21.1)
   Penta-drug
1 (6.3)
0
   Pomalidomide
4 (25.0)
1 (5.3)
   Anti-CD38 antibody
12 (75.0)
7 (36.8)
   Last line of prior therapy
8 (50.0)
10 (52.6)
Abbreviations: BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T cell; CD38, cluster of differentiation 38; ISS, International Staging System; Q2W, once every other week; QW, once every week.
Clinical data cutoff date of October 11, 2023.
aClinical examination or magnetic resonance imaging was used to document extramedullary sites of disease.
bdel(17p), t(4;14), and/or t(14;16).

Efficacy


MonumenTAL-2 (Cohort E): Efficacy Outcomes1
Parameter
TALVEY 0.4 mg/kg QW + Pomalidomide
(n=16)
TALVEY 0.8 mg/kg Q2W + Pomalidomide
(n=19)
Median follow-up, months (range)
15.0 (1.2-19.0)
11.1 (1.2-14.8)
ORR, n (%)
15 (93.8)
16 (84.2)
   sCR, %
43.8
26.3
   CR, %
18.8
10.5
   VGPR, %
25.0
31.6
   PR, %
6.3
15.8
≥CR, %
62.5
36.8
Median time to first response, months (range)
1.7 (0.9-3.3)
1.2 (0-4.8)
Median PFS, months (95% CI)
NR (14.09-NR)
NR (7.43-NR)
   9-month PFS rate, % (95% CI)
93.8 (63.2-99.1)
75.5 (46.4-90.3)
Median DOR, months (95% CI)
NR (12.0-NR)
NR (7.4-NR)
   9-month DOR rate, % (95% CI)
100.0 (100.0-100.0)
83.9 (49.4-95.7)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; NR, not reached; ORR, overall response rate; PFS, progression-free survival; PR, partial response; Q2W, once every other week; QW, once every week; sCR, stringent complete response; VGPR, very good partial response.
Clinical data cutoff date of October 11, 2023.

MonumenTAL-2 (Cohort E): ORR Across Patient Subgroups1
ORR in Subgroups, % (n/n)
TALVEY 0.4 mg/kg QW + Pomalidomide
TALVEY 0.8 mg/kg Q2W + Pomalidomide
CAR-T-exposeda
100 (3/3)
-
Pomalidomide-exposed
100 (5/5)
100 (3/3)
Extramedullary disease
50 (1/2)
67 (2/3)
High-risk cytogenetics
80 (4/5)
75 (3/4)
Abbreviations: CAR-T, chimeric antigen receptor T cell; ORR, overall response rate; Q2W, once every other week; QW, once every week.
aNo patients had CAR-T exposure in the TALVEY 0.8 mg/kg Q2W + pomalidomide cohort.

Safety

  • TEAEs that have been reported at a data cutoff date of October 11, 2023 are summarized in Table: MonumenTAL-2 (Cohort E): TEAEs.
  • Overall, infections of any grade were reported in 80.0% of patients (n=28) with grade 3/4 infections reported in 22.9% of patients (n=8).
    • First-onset infections generally occurred in the first few cycles of treatment.
    • One opportunistic esophageal candidiasis infection was recorded.
  • A total of 77.1% of patients had ≥1 postbaseline immunoglobulin G (IgG) value <400 mg/dL or hypogammaglobulinemia as a TEAE.
    • Overall, 34.3% of patients received intravenous immunoglobulin (IVIG) therapy.
  • Rash-related AEs (which included rash, maculopapular rash, erythema, and erythematous rash) occurred in 20.0% of patients (2.9% were grade 3/4), with no treatment discontinuations reported.
  • Cytokine release syndrome (CRS) of any grade was reported in 74.3% of patients (n=26) with grade 3/4 CRS reported in 2.9% of patients (n=1). CRS primarily occurred during step-up dosing and cycle 1.
    • A total of 45.7% of patients received tocilizumab for the treatment of CRS.
    • No additional CRS events occurred after the addition of pomalidomide at cycle 2.
  • ICANS occurred in 3 patients; all events were grade 1.
  • No treatment discontinuations due to nail-, taste-, or skin-related adverse events (AEs; presented as grouped terms) were reported.
  • Details on dose reductions and treatment discontinuations are provided in Table: MonumenTAL-2 (Cohort E): Dose Reductions/Schedule Change and Treatment Discontinuations.
    • Treatment discontinuations were reported in 4 patients (11.4%) due to pulmonary embolism, myocardial infarction, increased blood creatinine, and ICANS. The same patient who discontinued treatment, died due to pulmonary embolism.
    • A total of 62.9% of patients and 77.1% of patients skipped TALVEY and pomalidomide doses, respectively, due to AEs.

MonumenTAL-2 (Cohort E): TEAEs1
Event, n (%)
TALVEY + Pomalidomide (N=35)
Any Grade
Grade 3/4
Hematologica
   Neutropenia
22 (62.9)
19 (54.3)
   Anemia
13 (37.1)
9 (25.7)
   Thrombocytopenia
10 (28.6)
7 (20.0)
   Febrile neutropenia
-
3 (8.6)
Nonhematologic
   Taste-relatedb
30 (85.7)
NA
   CRS
26 (74.3)
1 (2.9)
   Skin-relatedc
26 (74.3)
2 (5.7)
   Nail-relatedd
24 (68.6)
0
   Dry mouth
19 (54.3)
0
   Fatigue
19 (54.3)
5 (14.3)
   Pyrexia
13 (37.1)
1 (2.9)
   Nausea
12 (34.3)
0
   Diarrhea
10 (28.6)
0
   Hypokalemia
10 (28.6)
2 (5.7)
   Back pain
9 (25.7)
1 (2.9)
   Headache
9 (25.7)
1 (2.9)
   Infections
28 (80.0)
8 (22.9)
      Pneumonia
8 (22.9)
5 (14.3)
      Upper respiratory tract infection
8 (22.9)
1 (2.9)
      COVID-19
6 (17.1)
1 (2.9)
      Oral candidiasis
3 (8.6)
0
      Urinary tract infection
3 (8.6)
1 (2.9)
      Influenza
2 (5.7)
0
      Respiratory syncytial virus infection
2 (5.7)
1 (2.9)
      Rhinovirus infection
2 (5.7)
0
      Sinusitis
2 (5.7)
0
Abbreviations: COVID-19, coronavirus disease 2019; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; NA, not available; TEAE, treatment-emergent adverse event.
Clinical data cutoff date of October 11, 2023.
aCytopenias were generally related to first few cycles.
bIncludes dysgeusia, ageusia, taste disorder, and hypogeusia. Per CTCAE, the maximum grade of dysgeusia is 2.
cIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysethesia syndrome.
dIncludes nail discoloration, nail disorder, nail toxicity, nail dystrophy, nail ridging, onychoclasis, onycholysis, and onychomadesis.

MonumenTAL-2 (Cohort E): Dose Reductions/Schedule Change and Treatment Discontinuations1
Parameter, n (%)
All Patients (N=35)
Dose reduction or schedule change of TALVEYa
12 (34.3)
Dose reduction or schedule change of pomalidomidea
16 (45.7)
Treatment discontinuationb
4 (11.4)
Deathc
1 (2.9)
Abbreviations: AE, adverse event.
aDose reductions were due to AEs. Dose reductions also included schedule change due to AE.
bRelated to at least 1 of the study treatment agents.
cDue to pulmonary embolism (same patient who discontinued treatment).

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 28 June 2024.

References

Show
1 Matous J, Biran N, Perrot A, et al. Talquetamab + pomalidomide in patients with relapsed/refractory multiple myeloma: safety and preliminary efficacy results from the phase 1b MonumenTAL-2 study. Oral Presentation presented at: 65th American Society of Hematology (ASH) Annual Meeting; December 9–12, 2023; San Diego, CA.  
2 Janssen Research & Development, LLC. A multi-arm phase 1b study of talquetamab with other anticancer therapies in participants with multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 June 28]. Available from: https://clinicaltrials.gov/ct2/show/NCT05050097. NLM Identifier: NCT05050097.  
3 Searle E, Quach H, Biran N, et al. Talquetamab, a GPRC5D×CD3 bispecific antibody, in combination with pomalidomide in patients with relapsed/refractory multiple myeloma: efficacy and safety results from the phase 1b monumenTAL-2 study. Poster presented at: The European Hematology Association (EHA) Annual Meeting; June 13-16, 2024; Madrid, Spain.