TALVEY®
(talquetamab-tgvs)
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TALVEY® (talquetamab-tgvs)
Medical Information
TALVEY - Dose Modifications
Last Updated: 11/04/2024
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 (LOT), including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody.1
- 3 - Dose modifications based on efficacy and safety in the MonumenTAL-1 study protocol are summarized below.3
- Chari et al (2024)4
published clinical management for adverse events (AEs) associated with TALVEY in patients with RRMM from the MonumenTAL-1 study. Dose modification strategies, including dose reductions, delays, or skips, were reported for the 0.4 mg/kg once every week (QW; n=143), 0.8 mg/kg once every other week (Q2W; n=145), and prior T-cell redirection (TCR) (n=51) cohorts. - Chari et al (2023)5
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 cohort (n=50) and October 2, 2023, in the prospective dose intensity reduction cohort (n=19).
- Banerjee et al (2024)6
presented a real-world, retrospective, observational, and descriptive cohort study describing TALVEY utilization patterns and dose schedules in patients with RRMM who were identified in the Multiple Myeloma Komodo Commercial Encounters (KCE) claims-based database and treated with TALVEY. The median follow-up time was 2.8 months (interquartile range [IQR], 2.0, 3.6). At the end of follow-up, among patients with ≥3 treatment doses after step-up dosing (SUD), 5/11 patients (45%) on QW dosing switched to Q2W or less-frequent dosing (LFD); 9/33 patients (27%) on Q2W dosing switched to once every three weeks (Q3W) or LFD.
Clinical Data - monumental-1 study
- Part 1 (phase 1; dose escalation): to characterize the safety of TALVEY and determine the recommended phase 2 doses (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.
Patients were enrolled into 1 of the following 3 cohorts1,9
- TCR therapy naïve: 0.4 mg/kg subcutaneously (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 naïve: 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 the type of TCR (CAR-T, BsAb or CAR-T and BsAb).
- Key eligibility criteria (Part 3; Phase 2):
- Key exclusion criteria (Part 3; Phase 2):
- Prior grade 3 or higher cytokine release syndrome (CRS, per Lee criteria 201410
) related to any TCR or any prior G protein-coupled receptor family 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
- Prior grade 3 or higher cytokine release syndrome (CRS, per Lee criteria 201410
- Primary endpoint: overall response rate.1
- Key secondary endpoints: duration of response, progression-free survival, 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
- SUD 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.
- SUD 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
- Per MonumenTAL-1 protocol (part 3), a switch from the 0.4 mg/kg SC QW dosing to a 0.8 mg/kg SC Q2W dosing schedule may occur at the start of the next cycle when a patient has had a complete response (CR) or better for a minimum of 6 months, after the decision has been made and if approved by the sponsor.3
- At data cutoff (January 17, 2023), 20 patients switched from 0.4 mg/kg SC QW to 0.8 mg/kg SC Q2W after a prolonged response to TALVEY. Hospitalization
(≥48 hours) was required after each step-up dose and Cycle 1 Day 1 dosing, but there was no requirement for hospitalization for switching from QW to Q2W after achieving a prolonged response.11,12
- At data cutoff (January 17, 2023), 20 patients switched from 0.4 mg/kg SC QW to 0.8 mg/kg SC Q2W after a prolonged response to TALVEY. Hospitalization
- Per MonumenTAL-1 protocol (part 3), dose delays are the primary method for managing AEs and toxicities.3
- Dose reductions or frequency changes could be considered after consultation with the sponsor.13
Results
Safety
- AEs resulted in treatment discontinuation in 4.9%, 8.3%, and 7.8% of patients and dose reductions in 14.7%, 8.3%, and 9.8% of patients in the 0.4 mg/kg QW, 0.8 mg/kg Q2W, and prior TCR cohorts, respectively.
- See Tables: Treatment Discontinuation due to Select TEAEs and Dose Modifications for Select TEAEs for additional details.
- Dose modification strategies, including reductions, delays, or skips, were advised as per investigator’s experience and were considered as effective management strategies for TEAEs.
| AE, n | TALVEY 0.4 mg/kg QW (n=143) | TALVEY 0.8 mg/kg Q2W (n=145) | Prior TCR (n=51) |
|---|---|---|---|
| Dysgeusia | - | 2 | - |
| Dysphagia | 0 | 0 | 0 |
| Dry mouth | 0 | 0 | 0 |
| Skin (rash-related) toxicity | 0 | 0 | 0 |
| Skin (nonrash-related) toxicity | 2a | 1b | 0 |
| Nail-related toxicity | 0 | 0 | 0 |
| Infections | 2 | 0 | 1 |
| CRS | - | 1 | 0 |
| ICANSc | 2 | 1 | - |
| Rare AEs | |||
| Alopecia | 0 | 0 | 0 |
| Abbreviations: AE, adverse event; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; Q2W, once every other week; QW, once every week; TCR, T-cell redirection therapy; TEAE, treatment-emergent adverse event. Clinical data cutoff date of January 17, 2023. aDue to skin exfoliation. bDue to dry skin. cAs ICANS was only assessed in phase 2 of the trial, the number of patients included in the analysis was 122, 109, and 34 in the 0.4 mg/kg QW, 0.8 mg/kg Q2W, and prior TCR cohorts, respectively. | |||
| AE, n (%) | TALVEY 0.4 mg/kg QW (n=143) | TALVEY 0.8 mg/kg Q2W (n=145) | Prior TCR (n=51) | |
|---|---|---|---|---|
| Dysgeusia | ||||
| Dose modification | 12 (8.4) | 8 (5.5) | 6 (11.8) | |
| Delayed | 0 (0) | 0 (0) | 0 (0) | |
| Skippeda | 7 (4.9) | 4 (2.8) | 5 (9.8) | |
| Reducedb | 10 (7.0) | 5 (3.4) | 4 (7.8) | |
| Dysphagia | ||||
| Dose modification | 2 (1.4) | 2 (1.4) | 3 (5.9) | |
| Delayed | 0 (0) | 0 (0) | 0 (0) | |
| Skippeda | 2 (1.4) | 1 (0.7) | 1 (2.0) | |
| Reducedb | 0 (0) | 1 (0.7) | 2 (3.9) | |
| Dry mouth | ||||
| Dose modification | 2 (1.4) | 4 (2.8) | 3 (5.9) | |
| Delayed | 0 (0) | 0 (0) | 0 (0) | |
| Skippeda | 2 (1.4) | 2 (1.4) | 2 (3.9) | |
| Reducedb | 1 (0.7) | 3 (2.1) | 2 (3.9) | |
| Skin (rash-related) toxicity | ||||
| Dose modification | 9 (6.3) | 6 (4.1) | 2 (3.9) | |
| Delayed | 1 (0.7) | 1 (0.7) | 0 (0) | |
| Skippeda | 7 (4.9) | 5 (3.4) | 2 (3.9) | |
| Reducedb | 1 (0.7) | 1 (0.7) | 0 (0) | |
| Skin (nonrash-related) toxicity | ||||
| Dose modification | 12 (8.4) | 1 (0.7) | 3 (5.9) | |
| Delayed | 1 (0.7) | 0 (0) | 0 (0) | |
| Skippeda | 9 (6.3) | 1 (0.7) | 3 (5.9) | |
| Reducedb | 5 (3.5) | 0 (0) | 1 (2.0) | |
| Nail-related toxicity | ||||
| Dose modification | 1 (0.7) | 0 (0) | 1 (2.0) | |
| Delayed | 0 (0) | 0 (0) | 0 (0) | |
| Skippeda | 1 (0.7) | 0 (0) | 1 (2.0) | |
| Reducedb | 1 (0.7) | 0 (0) | 0 (0) | |
| Infections | ||||
| Dose modification | 32 (22.4) | 29 (20.0) | 10 (19.6) | |
| Delayed | 1 (0.7) | 9 (6.2) | 0 (0) | |
| Skippeda | 31 (21.7) | 20 (13.8) | 9 (17.6) | |
| Reducedb | 0 (0) | 1 (0.7) | 1 (2.0) | |
| CRSc | ||||
| Dose modification | 18 (12.6) | 21 (14.5) | 3 (5.9) | |
| Delayed | 17 (11.9) | 21 (14.5) | 3 (5.9) | |
| Skippeda | 2 (1.4) | 2 (1.4) | 0 (0) | |
| Reducedb | 1 (0.7) | 1 (0.7) | 0 (0) | |
| ICANSc,d | ||||
| Dose modification | 2 (1.6) | 2 (1.8) | 0 (0) | |
| Delayed | 0 (0) | 2 (1.8) | 0 (0) | |
| Skippeda | 2 (1.6) | 0 (0) | 0 (0) | |
| Reducedb | 1 (0.8) | 0(0) | 0 (0) | |
| Abbreviations: AE, adverse event; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; LFD, less-frequent dosing; Q2W, once every other week; QW, once every week; TCR, T-cell redirection therapy; TCR, T-cell redirection, TEAE, treatment-emergent adverse event. Clinical data cutoff date of January 17, 2023. aDefined as patients who had at least 1 dose skip before resuming on the same dosing level and schedule thereafter. bDefined as changes to either a reduced dose or an LFD schedule. c≥1 treatment-emergent symptoms of CRS/ICANS leading to dose modification. d | ||||
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 or better (≥PR), 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.
- Responsive Dose Intensity Reduction Cohorts (n=50); after treatment at the RP2Ds, patients received reduced dose or less-frequent dose. Patients had partial response or better (≥PR), TEAE mitigation or both:
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: Duration of Response (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: Response and Duration of Response (Prospective Dose Intensity Reduction Cohorts).
| 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, once every week; TCR, T-cell redirection therapy. Clinical data cutoff date of October 11, 2023. 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). | |||
| 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
- A summary of the onset of TALVEY-associated AEs after switching at a data cutoff of October 2, 2023 is presented in Figure: Prospective Cohorts With Change in AE Status After Switch vs Matched Cohort Without Dose Reduction.
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.
Real-world study - TALVEY UTILIZATION PATTERNS AND DOSE SCHEDULES
Study Design/Methods
- The study included patients with MM treated with TALVEY, as identified in the MM KCE database, between August 9, 2023 (United States [US] approval date) and March 4, 2024.
- Patients were identified using Komodo Healthcare Map™. See Figure: Study Design: Tal Utilization Patterns and Dose Schedules for additional details.
- Eligibility criteria:
- Adult patients with ≥1 MM diagnosis code, ≥1 pharmacy or medical claim for TALVEY (between August 9, 2023 [US approval date], and March 4, 2024 [latest data cut]), and triple-class exposure were included in this study.
- Patients enrolled in clinical trials were excluded.
- Primary objective:
- To describe the demographic and clinical characteristics, treatment history, and TALVEY utilization patterns in patients treated with TALVEY from the MM KCE claims-based database.
Abbreviations: BCMA, B-cell maturation antigen; CAR-T, chimeric antigen receptor T-cell; MM, multiple myeloma; PI, protease inhibitor; SUD, step-up dosing; tal, talquetamab.
aData were collected from the Komodo Health payer-complete dataset.
bThe index date was the date of an inpatient TALVEY encounter that occurred within 28 days prior to the first TALVEY treatment dose (40 mg/mL) in the outpatient setting, or the date of the first outpatient TALVEY step-up dosing (SUD; 3 mg/1.5 mL) claim.
cDemographic characteristics included age, race, ethnicity, region, and payer channel.
dThe baseline period (used to describe patient demographic and clinical characteristics) was 6 months before the index date.
e
Results
Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics
- A total of 82 patients with RRMM treated with the TALVEY were included in this study. See Table: Demographic and Clinical Characteristics of Patients Treated With TALVEY for additional details.
- Median follow-up time of the study was 2.8 months (IQR, 2.0-3.6).
| Characteristic | Patients With RRMM With an eligible TALVEY Claim (n=82) |
|---|---|
| Age at index | |
| Age (years), median (IQR) | 65.0 (57.0-71.8) |
| ≥ 75 years, n (%) | 14 (17.1) |
| Sex, n (%) | |
| Male | 48 (58.5) |
| Female | 34 (41.5) |
| Race, n (%) | |
| White | 50 (65.8) |
| Black | 14 (18.4) |
| Hispanic | 3 (3.9) |
| Other/Unknown | 9 (11.8) |
| Comorbidities, n (%) | |
| Infections | 38 (46.3) |
| Peripheral neuropathy | 35 (42.7) |
| Hypogammaglobulinemia | 34 (41.5) |
| Extramedullary plasmacytoma | 3 (3.7) |
| Solitary plasmacytoma | 6 (7.3) |
| Plasma cell leukemia | 1 (1.2) |
| Prior LOT, n, median (IQR) | 5 (4-7) |
| Treatment history, n (%) | |
| Prior triple-class exposed | 82 (100) |
| Prior penta-drug exposed | 35 (42.7) |
| Prior therapiesa, n (%) | |
| Prior commercial BCMA-targeted therapy | 56 (68.3) |
| Teclistamab | 39.0 |
| Belantamab mafodotin-blmf | 20.7 |
| Idecabtagene vicleucel | 20.7 |
| Ciltacabtagene autoleucel | 7.3 |
| Elranatamab | 1.2 |
| Prior TCR therapies naïve | 39 |
| Abbreviations: IQR, interquartile range; LOT, line of therapy; RRMM, relapsed or refractory multiple myeloma; TCR, T-cell redirection. aSome patients had prior treatment with >1 therapy. | |
TALVEY Utilization
- A total of 89.0% of the patients (n=73) received TALVEY as monotherapy. See Table: TALVEY Utilization Patterns in Patients With RRMM.
- The first observed LFD schedule among patients who received ≥3 treatment doses after SUD is presented in Table: First Observed LFD Schedule.
- A total of 7/11 patients (63.6%) on QW switched to Q2W or LFD (median time to switching: 43 days), and 12/33 patients (36.4%) on Q2W switched to Q3W or LFD (median time to switching: not reached).
- At the end of the follow-up period, 5/11 patients (45%) on QW switched to Q2W or LFD, and 9/33 patients (27%) on Q2W dosing switched to Q3W or LFD. See Table: Dosing Frequency at the End of Follow-Up, by Initial Dosing Schedule.
- At the data cutoff, among patients with ≥3 treatment doses after SUD (n=50), 8 (16.0%), 32 (64.0%), and 6 (12.0%) patients were on QW, Q2W, and once every 4 weeks (Q4W) schedules, respectively.
| TALVEY Regimen, n (%)a | Patients With RRMM With an Eligible TALVEY Claim (n=82) |
|---|---|
| TALVEY | 73 (89.0) |
| TALVEY + Teclistamab | 3 (3.7) |
| TALVEY + Pomalidomide | 2 (2.4) |
| TALVEY + Bortezomib | 1 (1.2) |
| TALVEY + Daratumumab + Carfilzomib + Ixazomib | 1 (1.2) |
| TALVEY + Daratumumab | 1 (1.2) |
| TALVEY + Isatuximab + Pomalidomide | 1 (1.2) |
| Abbreviation: RRMM, relapsed or refractory multiple myeloma. aCombination regimens were identified within 2 months following the initiation of TALVEY. | |
| Initial treatment frequency | First LFD, n (%) | |||
|---|---|---|---|---|
| Q2W (12-17 days) | Q3W (18-24 days) | Q4W (25-31 days) | Other (≥32 days) | |
| QW (6-11 days; n=11) | 6 (54.5) | 0 | 0 | 1 (9.1) |
| Q2W (12-17 days; n=33) | NA | 4 (12.1) | 6 (18.2) | 2 (6.1) |
| Abbreviations: LFD, less-frequent dosing; NA, not applicable; Q2W, once every other week; Q3W; once every 3 weeks; Q4W; once every 4 weeks; QW, once every week. aAmong patients who received ≥3 treatment doses after SUD, the first observed LFD was defined as having ≥2 consecutive doses administered at a lower frequency than the initial treatment schedule. | ||||
| Frequency of the First Treatment | Frequency at the End of Follow-Up, n (%) | ||||
|---|---|---|---|---|---|
| QW (6-11 days) | Q2W (12-17 days) | Q3W (18-24 days) | Q4W (25-31 days) | Other (≥32 days) | |
| QW (6-11 days; n=11) | 6 (54.5) | 4 (36.4) | 0 | 0 | 1 (9.1) |
| Q2W (12-17 days; n=33) | 2 (6.1) | 22 (66.7) | 2 (6.1) | 6 (18.2) | 1 (3.0) |
| Abbreviations: Q2W, once every other week; Q3W; once every 3 weeks; Q4W; once every 4 weeks; QW, once every week. aAmong patients with ≥3 treatment doses after SUD. | |||||
literature search
A literature search of MEDLINE®
References
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