TALVEY®
(talquetamab-tgvs)
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TALVEY® (talquetamab-tgvs)
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TALVEY - Clinical Outcomes of Subsequent Therapies Following TALVEY
Last Updated: 05/22/2024
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 (LOTs), including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-cluster of differentiation 38 (anti-CD38) monoclonal antibody.1
- 3 - Sanchez et al (2023)4
presented (at the 65th American Society of Hematology [ASH] Annual Meeting) the clinical outcomes of subsequent therapies in patients with no prior T-cell redirection (TCR) therapy following TALVEY treatment in the MonumenTAL-1 study. Responses were observed in patients receiving TCR therapies following TALVEY treatment. Overall, 35% of patients who received chimeric antigen receptor T-cell therapy (CAR-T) and 30% of patients who received non-G protein-coupled receptor family C group 5 member D (GPRC5D) as the first LOT after TALVEY treatment achieved a complete response or better (≥CR).
- Sanchez et al (2023)4
- Shrestha et al (2024)5
presented a case series analyzing the effectiveness of B-cell maturation antigen (BCMA)-based therapy in patients with RRMM who were previously treated with TALVEY. At a median follow-up of 9.5 months (range, 6-24), overall response rate (ORR) was 60% and median progression free survival (PFS) was 5.5 months (range, 1-10) for the first BCMA therapy post TALVEY.
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 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.
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 cohorts6
- TCR naive: 0.4 mg/kg subcutaneous (SC) weekly (QW) (n=143), not previously exposed to TCRs such as CAR-T or bispecific antibodies (BsAbs; prior BCMA antibody-drug conjugate [ADC] allowed).
- TCR naive: 0.8 mg/kg SC once every other week (Q2W; n=154), not previously exposed to TCRs (prior BCMA ADC allowed).
- Prior TCR: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W (n=70), previously exposed to TCRs.
- Key eligibility criteria (Part 3; phase 2):
- Primary endpoint: ORR.1
- Key secondary endpoints: duration of response, PFS, overall survival, safety
, immunogenicity, and pharmacodynamics.1 - Dosing
- Following 2-3 step-up doses, patients received TALVEY 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W.4
- Following 2-3 step-up doses, patients received TALVEY 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W.4
Study Design/Methods
- Of the 297 patients in MonumenTAL-1 who had no prior TCR (0.4 mg/kg QW cohort, n=143; 0.8 mg/kg Q2W cohort; n=154), 162 patients who received ≥1 subsequent therapy after TALVEY were analyzed.4
- Subsequent therapy, start and end dates of therapy, and ORR on subsequent therapy (based on investigator-reported assessment) were recorded.4
Results
Patient Characteristics and Subsequent Therapies Received
- Baseline characteristics of the patients receiving subsequent therapies following TALVEY are described in Table: MonumenTAL-1: Baseline Characteristics of Patients Receiving Subsequent Therapies Following TALVEY.4
Subsequent Therapies Received
- LOTs received following TALVEY are presented in Table: MonumenTAL-1: Lines of Therapies Received Following TALVEY.4
Timing of Subsequent Therapies
- Across all the therapies, the median time from treatment with TALVEY to the start of the first subsequent therapy was 1 month.4
- Patients discontinued TALVEY due to disease progression (80.9%), investigator decision (13.6%), adverse events (4.3%), or withdrawal from MonumenTAL-1 (1.2%). Patients who discontinued TALVEY due to disease progression or adverse events received first subsequent therapy after a median of 0.7 months and 4.9 months, respectively.
- The median time to next treatment from the first to second subsequent therapy was 1.0 month; from the second to third subsequent therapy was 0.4 months and from the third to fourth subsequent therapy was 0.4 months.4
| Characteristic | 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W (n=162) |
|---|---|
| Median age (range), years | 64.5 (42-81) |
| Male, n (%) | 93 (57.4) |
| Extramedullary plasmacytomas ≥1,a | 48 (29.6) |
| High risk cytogenetic profile,b | 38 (27.5) |
| Median prior lines of therapy (range) | 5 (2-17) |
| Exposure status, n (%) | |
| Triple-classc | 162 (100) |
| Penta-drugd | 117 (72.2) |
| Belantamab | 20 (12.3) |
| Refractory status, n (%) | |
| Triple-classc | 122 (75.3) |
| Penta-drugd | 47 (29.0) |
| To last prior line of therapy | 154 (95.1) |
| Abbreviations: CD38, cluster of differentiation 38; mAb, monoclonal antibody; PI, proteasome inhibitor; Q2W, once every other week; QW, weekly; SC, subcutaneous. aSoft tissue plasmacytomas not associated with the bone were included bdel(17p), t(4;14), and/or t(14;16); calculated from n=138 for the QW cohort and n=128 for the Q2W cohort. c≥1 PI, ≥1 immunomodulatory drug, and ≥1 anti-CD38 mAb. d≥2 PIs, ≥2 immunomodulatory drugs, and ≥1 anti-CD38 mAb. | |
| Treatment Regimena | Frequency, n (%)b | |||
|---|---|---|---|---|
| First LOT | Second LOT | Third LOT | Fourth LOT | |
| Therapies received following TALVEY | 156 (96.3) | 69 (42.6) | 29 (17.9) | 12 (7.4) |
| Chemotherapy-based regimens | 48 (29.6)c | 20 (12.3)d | 8 (4.9)d | 4 (2.5)d |
| PI-, immunomodulatory drug-, or other anti-neoplastic-containing regimens | 44 (27.2)e | 17 (10.5)f | 6 (3.7)f | 1 (0.6)f |
| Anti-CD38 mAb-containing regimens | 27 (16.7)g | 7 (4.3)h | 4 (2.5)h | 1 (0.6)h |
| CAR-T | 17 (10.5)i | 13 (8.0)j | 1 (0.6)j | 2 (1.2)j |
| Anti-BCMA CAR-T | 9 (5.6) | 8 (4.9) | 0 | 2 (1.2) |
| Non-GPRC5D BsAbs | 23 (14.2)k | 13 (8.0)l | 8 (4.9)l | 3 (1.9)l |
| Anti-BCMA BsAbs | 19 (11.7) | 12 (7.4) | 8 (4.9) | 3 (1.9) |
| Anti-FcRH5 BsAbsm | 4 (2.5) | 1 (0.6) | 0 | 0 |
| Immune-based therapyn | 2 (1.2) | 0 | 2 (1.2) | 1 (0.6) |
| Anti-BCMA ADC-based therapy | 9 (5.6) | 4 (2.5) | 1 (0.6) | 1 (0.6) |
| Abbreviations: ADC, antibody-drug conjugate; BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CART, chimeric antigen receptor T-cell therapy; CD38, cluster of differentiation 38; FcRH5, Fc receptor-like protein 5; GPRC5D, G protein-coupled receptor family C group 5 member D; LOT, line of therapy; mAb, monoclonal antibody; PI, proteasome inhibitor aPatients could receive ≥1 subsequent therapy at any time. bPercentages are calculated with the number of patients who received any subsequent therapy (n=162) as denominator. cIncludes 27 different regimens. dIncludes 16, 8, and 4 different regimens at second, third, and fourth line of subsequent therapy, respectively. eIncludes 26 different regimens. fIncludes 14, 6, and 1 different regimens at second, third, and fourth line of subsequent therapy, respectively. gIncludes 16 different regimens. hIncludes 6, 4, and 1 different regimens at second, third, and fourth line of subsequent therapy, respectively. iCAR-T includes 11 different regimens; anti-BCMA CAR-T is included as a subcategory. jIncludes 7, 1, and 2 different regimens at second, third, and fourth line of subsequent therapy, respectively; anti-BCMA CAR-T is included as a subcategory. kReceived as monotherapies in 36.8% (anti-BCMA BsAbs) and 100% (anti-FcRH5 BsAbs) of patients. lReceived as monotherapies as second subsequent therapy in 58.3% (anti-BCMA BsAbs) and 100% (anti-FcRH5 BsAbs) of patients, as third subsequent therapy in 100% of patients, and as fourth subsequent therapy in 66.6% of patients. mDoses ranged from 3.6 mg to 252 mg. nNon-CAR-T, non-BsAb. | ||||
Efficacy
- At the data cutoff date of October 2023, in patients who received subsequent therapies, the median treatment duration with TALVEY was 5.8 months. ORR with TALVEY was 62.3% (≥CR, 20.4%), which was lower than that of the overall population (>71%).4
- Responses with first line of subsequent therapies are presented in Table: MonumenTAL-1: Responses With First Line of Subsequent Therapy.4
- ORRs in patients who received subsequent therapy with anti-Fc receptor-like protein 5 (FcRH5) BsAbs, anti-BCMA ADC-based therapy, and other immune-based therapies were 75.0% (n/N=3/4), 33.3% (n/N=3/9), and 0.0% (n/N=0/2), respectively.4
- Among both responders and nonresponders to CAR-T and non-GPRC5D BsAbs as subsequent therapies, response to prior TALVEY was similar, indicating response to TALVEY did not determine response to subsequent TCR therapies.4
- In patients receiving subsequent TCR therapies, responses were achieved regardless of line of subsequent therapy, or interval from prior TALVEY. Details are described in Table: MonumenTAL-1: ORR by Line of Subsequent T-cell Redirection Therapy and Respective Intervals Between Subsequent Therapies.4
| Therapy, % | ≥CR | sCR | CR | VGPR | PR |
|---|---|---|---|---|---|
| T-cell redirection therapies | |||||
| CAR-Tb | 35.3 | 29.4 | 5.9 | 17.6 | 11.8 |
| Anti-BCMA CAR-T | 33.3 | 33.3 | 0 | 22.2 | 22.2 |
| Non-GPRC5D BsAbsc | 30.4 | 4.3 | 26.1 | 21.7 | 8.7 |
| Anti-BCMA BsAbs | 31.6 | 0 | 31.6 | 21.1 | 5.3 |
| Conventional therapies | |||||
| Chemotherapy-based regimens | 0 | 0 | 0 | 4.2 | 14.6 |
| PI-, immunomodulatory drug-, or other anti- neoplastic-containing regimens | 2.3 | 0 | 2.3 | 11.6 | 7.0 |
| Anti-CD38 mAb-containing regimens | 14.8 | 3.7 | 11.1 | 11.1 | 7.4 |
| Abbreviations: BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T-cell therapy; CD38, cluster of differentiation 38; CR, complete response; GPRC5D, G protein-coupled receptor family C group 5 member D; mAb, monoclonal antibody; ORR, overall response rate; PI, proteasome inhibitor; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. aDue to rounding, individual response rates may not sum to the ORR. bCAR-T includes anti-BCMA CAR-T as a subgroup. cNon-GPRC5D BsAbs include anti-BCMA BsAbs as a subgroup. | |||||
| Therapy | Line of Therapy (n) | ORR on Subsequent Therapy, % (n) | Median Interval From TALVEY to Subsequent Therapy (Range), Months |
|---|---|---|---|
| CAR-T | First (17) | 64.7 (11/17) | 0.9 (0.1-7.4) |
| Second (12) | 53.8 (7/13) | 5.6 (1.7-14.8) | |
| Third (1) | 0 (0/1) | 8.0 (8.0-8.0) | |
| Fourth (2) | 50.0 (1/2) | 5.3 (5.2-5.5) | |
| Anti-BCMA BsAbs | First (19) | 57.9 (11/19) | 1.4 (0.7-11.0) |
| Second (12) | 33.3 (4/12) | 6.2 (1.9-20.2) | |
| Third (8) | 62.5 (5/8) | 8.6 (5.5-16.8) | |
| Fourth (3) | 33.3 (1/3) | 11.4 (8.4-15.2) | |
| Anti-FcRH5 BsAbs | First (4) | 75.0 (3/4) | 1.2 (1.0-2.3) |
| Second (1) | 0 (0/1) | 5.1 (5.1-5.1) | |
| Abbreviations: BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CAR-T, chimeric antigen receptor T-cell therapy; FcRH5, Fc receptor-like protein 5; ORR, overall response rate. | |||
CLINICAL DATA – CASE REPORTS
Study Design/Methods
- This retrospective study included patients with RRMM (N=10) who received BCMA-based therapy subsequent to TALVEY progression at the University of Arkansas for Medical Sciences.
- Eligible patients were previously treated with a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
- PFS was estimated from the start of BCMA-based treatment to disease progression, death, or last follow-up.
Results
Patient Characteristics and Subsequent Therapies Received
- Baseline characteristics of patients receiving subsequent therapies following TALVEY are described in Table: Baseline Characteristics at the Initiation of First BCMA Therapy After TALVEY.
Subsequent Therapies Received
- Subsequent therapies received following TALVEY are presented in Table: Subsequent Therapies Received Following TALVEY.
| Characteristic | Total (N=10) |
|---|---|
| Median age at diagnosis (range), years | 61 (56-75) |
| Median age at first BCMA therapy (range), years | 71 (59-81) |
| Gender, n (%) | |
| Male | 5 (50) |
| Female | 5 (50) |
| Race, n (%) | |
| White | 4 (40) |
| Black | 6 (60) |
| R-ISS at diagnosis, n (%) | |
| 1 | 3 (30) |
| 2 | 5 (50) |
| 3 | 2 (20) |
| Myeloma subtype, n (%) | |
| IgG | 6 (60) |
| IgA | 1 (10) |
| Light chain | 3 (30) |
| ECOG PS, n (%) | |
| 1 | 7 (70) |
| 2 | 3 (30) |
| Cytogenetics, n (%) | |
| High risk | 6 (60) |
| Standard risk | 4 (40) |
| Plasma cell leukemia, n (%) | 0 |
| Triple refractory,a n (%) | 10 (100) |
| Penta refractory,b n (%) | 8 (80) |
| Median prior lines of therapy (range) | 6 (5-12) |
| Number of prior stem cell transplants, n (%) | |
| 0 | 1 (10) |
| 1 | 5 (50) |
| 2 | 1 (10) |
| 3 | 2 (20) |
| 5 | 1 (10) |
| PET scan ≥3 focal lesions, n (%) | 6 (60) |
| Extramedullary disease, n (%) | 5 (50) |
| Median serum creatinine (range), mg/dL | 1.3 (0.7-1.6) |
| Median hemoglobin (range), g/dL | 10.4 (8.8-12.4) |
| Median absolute neutrophil count (range), x 103/µL | 2.85 (0.3-3.4) |
| Median absolute lymphocyte count (range), x 103/µL | 0.98 (0.02-2.37) |
| Median platelet count (range), x 103/µL | 154 (18-257) |
| Abbreviations: BCMA, B-cell maturation antigen; CD, cluster of differentiation; ECOG PS, Eastern Cooperative Oncology Group performance status; Ig, immunoglobulin; PET, positron emission tomography; PI, proteosome inhibitor; R-ISS, Revised International Staging System. aAt least 1 PI, 1 immunomodulatory drug, and 1 anti-CD38 antibody. bAt least 2 PIs, 2 immunomodulatory drugs, and 1 anti-CD38 antibody. | |
| Therapy, n | Total (N=10) |
|---|---|
| First BCMA after TALVEY | 10 |
| Belantamab mafodotin | 3 |
| Belantamab mafodotin/pomalidomide/dexamethasone | 1 |
| CAR-T (idecabtagene vicleucel) | 3 |
| TECVAYLI | 2 |
| ABBV-383/pomalidomide/dexamethasone | 1 |
| Second BCMA after TALVEYa | 3 |
| TECVAYLI | 2 |
| CAR-T (idecabtagene vicleucel) | 1 |
| Abbreviations: ABBV-383, anti-BCMA x CD3 bispecific antibody; BCMA, B-cell maturation antigen; CAR-T, chimeric antigen receptor T-cell therapy. aSecond BCMA agent post TALVEY after progression with the first BCMA-based therapy. | |
Efficacy
- ORR was 60%, and median PFS was 4 months (range, 1-15) in the 10 TALVEY-treated patients.
- At a median follow-up of 9.5 months (range, 6-24), ORR was 60% and median PFS was 5.5 months (range, 1-10) for the first BCMA therapy post TALVEY. At data cutoff, 3 patients who received the first BCMA agent post TALVEY have not progressed yet.
- Details on subsequent treatments and responses are presented in Table: Subsequent Therapies and Responses Following TALVEY.
| Patient | Best Response to TALVEYa | First BCMA therapy | Best Responsea | Response in 3 Months | Response in 6 Months | Prior EMD | EMD After Therapy | Second BCMA therapy | Best Responsea | Response in 3 Months | Response in 6 Months | Prior EMD | EMD After Therapy |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1b | sCR | CAR-T | CR | PR | PD | X | X | TECVAYLI | VGPR | VGPR | CRc | X | R |
| 2 | sCR | ABBV-383 + pomalidomide | sCR | sCR | sCRc | X | R | - | - | - | - | - | - |
| 3 | CR | Belantamab mafodotin | PD | PD | - | - | - | TECVAYLI | SD | PD | Death | X | X |
| 4 | CR | CAR-T | sCR | SD | CRb | - | - | - | - | - | - | - | - |
| 5 | VGPR | Belantamab mafodotin | SD | PD | - | X | X | - | - | - | - | - | - |
| 6 | PR | CAR-T | PR | PR | PRb | - | - | - | - | - | - | - | - |
| 7 | SD | Belantamab mafodotin | PD | PD | - | X | X | - | - | - | - | - | - |
| 8b | SD | TECVAYLI | VGPR | PR | VGPR | - | - | - | - | - | - | - | - |
| 9 | SD | TECVAYLI | SD | PD | - | - | - | - | - | - | - | - | - |
| 10 | PD | Belantamab mafodotin/ pomalidomide/dexamethasone | VGPR | PR | VGPR | X | X | CAR-T | PR | PR | PR | X | R |
| Abbreviations: ABBV-383, anti-BCMA x CD3 bispecific antibody; BCMA, B-cell maturation antigen; CAR-T, chimeric antigen receptor T-cell therapy; CD, cluster of differentiation; CR, complete response; EMD, extramedullary disease; IMWG; International Myeloma Working Group; PD, progressive disease; PR, partial response; R, resolution of EMD after subsequent therapies, sCR, stringent complete response; SD, stable disease; VGPR, very good partial response; -, data not available. aIMWG criteria was used to define treatment responses. bIndicates the patient has received BCMA agents before TALVEY. cIndicates ongoing response. | |||||||||||||
Safety
- TALVEY treatment resulted in mostly grade 0-1 cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS).
- The treatment with different subsequent therapies post TALVEY showed varied CRS and ICANS profiles in patient groups. Treatment sequence and adverse events in patients are presented in Table: Treatment Sequence and CRS/ICANS.
| Patient | First Treatment | CRS Max Gradea | ICANS Max Gradea | Second Treatment | CRS Max Gradea | ICANS Max Gradea | Third Treatment | CRS Max Gradea | ICANS Max Gradea |
|---|---|---|---|---|---|---|---|---|---|
| 1b | TALVEY | 1 | 0 | CAR-T | 1 | 0 | TECVAYLI | 1 | 0 |
| 2 | TALVEY | 1 | 0 | ABBV-383 + pomalidomide | 1 | 0 | - | - | - |
| 3 | TALVEY | 2 | 2 | Belantamab mafodotin | 0 | 0 | TECVAYLI | 0 | 0 |
| 4 | TALVEY | 1 | 0 | CAR-T | 1 | 0 | - | - | - |
| 5 | TALVEY | 1 | 1 | Belantamab mafodotin | 0 | 0 | - | - | - |
| 6c | TALVEY | 0 | 0 | CAR-T | 1 | 2 | - | - | - |
| 7 | TALVEY | 1 | 0 | Belantamab mafodotin | 0 | 0 | - | - | - |
| 8b | TALVEY | 0 | 0 | TECVAYLI | 0 | 0 | - | - | - |
| 9d | TALVEY | 0 | 0 | TECVAYLI | 0 | 3 | - | - | - |
| 10 | TALVEY | 0 | 0 | Belantamab mafodotin/ pomalidomide/ dexamethasone | 0 | 0 | CAR-T | 0 | 0 |
| Abbreviations: ABBV-383, anti-BCMA x CD3 bispecific antibody; ASTCT, American Society for Transplantation and Cellular Therapy; BCMA, B-cell maturation antigen; CAR-T, chimeric antigen receptor T-cell therapy; CD, cluster of differentiation; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; max, maximum. aASTCT criteria were used to grade CRS and ICANS. bIndicates the patient has received BCMA agents before TALVEY. cICANS resolved within 24 hours after dexamethasone and tocilizumab administration. dDischarged to hospice. | |||||||||
Literature Search
A literature search of MEDLINE®
References
| 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. Oral Presentation presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 2-6, 2023; Chicago, IL/Virtual. |
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