Summary

• Janssen does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
• Nail toxicity has been reported as an adverse event (AE) in the MonumenTAL-1, MonumenTAL-2, TRIMM2, and RedirecTT-1 studies.^1-7
• 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.^1,4,8-10
  • Schinke et al (2024)¹¹ presented the incidence of nail-related AEs from a subgroup analysis in Black and White patients at a median follow-up of 26 months for the Black subgroup and 31 months for the White subgroup. The subgroup of patients received TALVEY at the recommended phase 2 doses (RP2Ds) of 0.4 mg/kg subcutaneous (SC) weekly (QW) and 0.8 mg/kg SC every other week (Q2W).
  • Rasche et al (2024)¹² presented the incidence of nail-related AEs 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 T-cell redirection (TCR) therapy exposed cohort.
  • Chari et al (2024)¹³ published the clinical management of AEs in patients with RRMM treated with TALVEY in the MonumenTAL-1 study. Nail-related AEs were reported in the QW, Q2W, and TCR cohorts.
  • Jakubowiak et al (2023)¹⁴ presented the incidence of nail-related AEs in patients with prior TCR, including an additional 19 patients enrolled in the MonumenTAL-1 study since the prior analysis, at a median follow-up of 18.4 months for the overall prior TCR cohort, 18.4 months for the prior chimeric antigen receptor modified T-cells (CAR-T) cohort, and 16.3 months for the prior bispecific antibody (BsAb) cohorts.
  • Chari et al (2023)¹⁵ presented the incidence of nail-related AEs in patients from the Prospective Dose Intensity Reduction Cohorts of the MonumenTAL-1 study at a median follow-up of 13.2 months.
  • Krishnan et al (2023)¹⁶ evaluated the incidence of nail-related AEs in key high-risk and prior B-cell maturation antigen (BCMA) therapy subgroups of patients from the MonumenTAL-1 study.
  • Chari et al (2022)^4,5 published the incidence of nail-related AEs in the phase 1 portion of the MonumenTAL-1 study. Patients received TALVEY at the first RP2D of 0.405 mg/kg SC QW (median follow-up, 11.7 months), or at the second RP2D of 0.8 mg/kg SC Q2W (median follow-up, 4.2 months).
  • As per the MonumenTAL-1 study (part 3) protocol, nail dysfunctions, including, but not limited to, brittle nails, cracking nails, painful nails, and loss of nails, were managed symptomatically using nail soaks, topical moisturizers, and topical steroids. Persistent nail complications were evaluated by a dermatologic consult.¹⁰
• MonumenTAL-2 (MMY1004) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY + other anticancer therapies in patients with multiple myeloma (MM).^6,17-19
  • Cohort D is evaluating the efficacy and safety of TALVEY + DARZALEX FASPRO^® (daratumumab hyaluronidase) and lenalidomide in 34 patients with newly diagnosed multiple myeloma (NDMM).¹⁸
    • Nooka et al (2024)¹⁸ presented the incidence of nail-related AEs of the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 13.2 months (range, 10.0-14.6) and the TALVEY 0.8 mg/kg every 4 weeks (Q4W) + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 5.8 months (range, 1.7 [denotes patients who died]-12.0).
  • Cohort E is evaluating the safety and efficacy of TALVEY + pomalidomide in 35 patients with RRMM.¹⁹
    • Searle et al (2024)¹⁹ presented the incidence of nail-related AEs of TALVEY + pomalidomide from the MonumenTAL-2 study at a median follow-up of 16.8 months (range, 1.2-25.1).
• RedirecTT-1 (MMY1003) is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY and TECVAYLI^® (teclistamab-cqyv) combination in patients with RRMM.^3,7,9,20
  • Cohen et al (2025)⁷ published the incidence of nail-related AEs from the phase 1 dose-escalation segment of the RedirecTT-1 study at a median follow-up of 20.3 months (range, 0.5-37.1) in the all dose levels (dose levels 1-5) cohort.
• TRIMM-2 (MMY1002) is an ongoing, phase 1b, multicohort open-label study evaluating the efficacy and safety of DARZALEX FASPRO + TECVAYLI or TALVEY with or without pomalidomide in patients with RRMM.^2,8,21
  • Bahlis et al (2024)²¹presented the incidence of nail-related AEs of the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 15.8 months (range, 3.2-37.9) and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 17.5 months (range, 0.2-37.7).
  • Dholaria et al (2023)² presented the incidence of nail-related AEs from the TALVEY + DARZALEX FASPRO cohorts at a median follow-up of 16.8 months for the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO cohort and 15.0 months for the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO cohort.
• Other relevant literature has been identified in addition to the data summarized above:
  • Retrospective descriptive studies reported nail toxicities.²²
  • Case reports and case series reported nail toxicities.^23-26
  • Nursing and advance practice practitioner’s considerations for management of nail toxicities.^27-30
  • Real-world evidence describing and managing skin toxicities.³¹

PRODUCT LABELING

• TALVEY (talquetamab-tgvs) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.
• TECVAYLI (teclistamab-cqyv) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf.

BACKGROUND

• G protein-coupled receptor, class C, group 5, member D (GPRC5D) is a 7-segment transmembrane orphan receptor protein that belongs to the family of G-protein-coupled receptors.³² It is predominantly expressed in cells with a plasma-cell phenotype, with higher expression levels on the surface of malignant plasma cells in patients with MM, thereby making it a potential immunotherapeutic target.^33-35 It is also found to be expressed in plasma cells and hard, keratinized tissues, such as skin and nails.^36-38
• TALVEY may cause nail toxicity by targeting highly proliferating cells, such as those in the nail matrix, with GPRC5D receptors present on them.²⁴

Clinical Data - MONUMENTAL-1 STUDY

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^39,40

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

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

Study Design/Methods (Phase 2)

Patients were enrolled into 1 of the following 3 cohorts^1,14:

• TCR naïve: 0.4 mg/kg SC QW, not previously exposed to TCR such as CAR-T therapy or BsAbs (prior 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):
  • Measurable MM.¹⁴
  • ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.¹⁴
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.¹⁴
• Key exclusion criteria (Part 3; Phase 2):
  • Prior grade 3 or higher cytokine release syndrome (CRS; per Lee criteria 2014⁴¹) related to any TCR or any prior GPRC5D-targeting therapy.¹⁰
  • Received cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within 14 days prior to study drug (not including premedication).¹⁰
• Primary endpoint: overall response rate (ORR).¹
• Key secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival, safety, immunogenicity, and pharmacodynamics.¹

Schinke et al (2024)¹¹ presented the incidence of nail-related AEs from a subgroup analysis in Black patients who received TALVEY at the RP2Ds of 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W in phase 1/2 of the MonumenTAL-1 study at a median follow-up of 26 months for the Black subgroup and 31 months for the White subgroup.

Safety Results

• Details on GPRC5D-associated nail-related AEs are summarized in Table: MonumenTAL-1 Study: Summary of Nail-Related AEs in Black vs White Patients.

Rasche et al (2024)¹² presented the incidence of nail-related AEs from the MonumenTAL-1 study in patients receiving TALVEY at a median follow-up of 29.8 months for the 0.4 mg/kg SC QW cohort, 23.4 months for the 0.8 mg/kg SC Q2W cohort, and 20.5 months for the prior TCR cohort.

Safety Results

• Details on GPRC5D-associated nail-related AEs are summarized in Table: MonumenTAL-1 Study: GPRC5D-Associated Nail-Related AEs.

Chari et al (2024)¹³ published the clinical management of AEs in patients with RRMM treated with TALVEY in the MonumenTAL-1 study. Results specific to nail-related toxicities are summarized below.

Safety Results

• In the MonumenTAL-1 study, nail toxicities (on fingers and toes) included nail discoloration, nail disorder, onycholysis [separation of the nail from its nail bed], onychomadesis [detachment of the nail from its nail bed], onychoclasis [nail breakage], nail dystrophy, nail toxicity, and nail ridging).
• A summary of nail-related AEs associated with TALVEY in MonumenTAL-1 is presented in Table: MonumenTAL-1 Study: Nail-Related AEs Associated With TALVEY.
• All nail-related AEs were grade 1/2, and many events persisted over the course of treatment.
• The median total duration that patients experienced nail toxicities across all events was 220.5 days (range, 6-832) across the 0.4 mg/kg QW, 0.8 mg/kg Q2W and prior TCR cohorts.
• Few dose modifications occurred for nail-related toxicities, and no treatment discontinuations were reported due to nail-related toxicities.

Supportive Measures/Management

• The MonumenTAL-1 protocol recommends managing nail toxicities with nail soaks, topical moisturizers, and topical corticosteroids.
  • Emollients were commonly used; investigators also considered the use of vitamin E oil, systemic hydration, biotin, triamcinolone 0.025% ointment, and protective coverings like socks and gloves at night for managing nail toxicities.
  • Occlusion may be used to concentrate the effect of topical corticosteroids and moisturizers.
  • Nail hardeners, acrylics, and gels should be avoided to prevent fungal infections.
• Concomitant medications were also used to manage nail toxicities in all 3 cohorts. See Table: MonumenTAL-1 Study: Most Common Supportive Measures and Concomitant Treatments for Nail Toxicities for additional details.
• Nail assessments should be part of the physical examination during TALVEY therapy.

Jakubowiak et al (2023)¹⁴presented the incidence of nail-related AEs in patients with prior TCR, including an additional 19 patients enrolled in the MonumenTAL-1 study since the prior analysis, at a median follow-up of 18.4 months for the overall prior TCR cohort and the prior CAR-T cohort and 16.3 months for the prior BsAb cohort.

Safety Results

• Patients with prior exposure to CAR-T had similar rates of nail-related AEs compared with patients with prior exposure to BsAb.
• A summary of nail-related AEs in patients with prior TCR is presented in Table: MonumenTAL-1 Study: Nail-Related AEs (Prior TCR).

Chari et al (2023)¹⁵ presented the incidence of nail-related AEs of patients in MonumenTAL-1 who switched to reduced or less frequent dosing with TALVEY at a median follow-up of 13.2 months.

Study Design/Methods

• Patients were divided into Responsive Dose Intensity Reduction Cohorts and Prospective Dose Intensity Reduction Cohorts.
  • 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 partial response or better (≥PR).
    • TALVEY 0.8 mg/kg Q2W was reduced to 0.8 mg/kg Q4W in 10 patients who had ≥PR.

Safety Results

• At a data cutoff of October 2, 2023, prospective cohorts showed a trend toward improved resolution of nail-related AEs after switch. Resolution of nail-related AEs after switching to less frequent or lower intensity dosing of TALVEY are presented in Figure: MonumenTAL-1 Study: Prospective Cohorts With Change in Nail Toxicity After Switch vs Matched Cohort Without Dose Reduction.

Krishnan et al (2023)¹⁶ evaluated the incidence of nail-related AEs of TALVEY in key high-risk and prior BCMA therapy subgroups of patients from the phase 1/2 MonumenTAL-1 study.

Safety Results

• Nail-related AEs observed in the high-risk patient subgroups are summarized in Table: MonumenTAL-1 Study: Summary of Nail-Related AEs in High-risk Subgroups.
• Nail-related AEs observed in the prior BCMA therapies subgroups are summarized in Table: MonumenTAL-1 Study: Summary of Nail-Related AEs in Prior BCMA Subgroups.

Chari et al (2022)⁴ published the incidence of nail-related AEs from the phase 1 portion of the MonumenTAL-1 study at a median follow-up of 11.7 months (range, 1.0-21.2) for the 0.405 mg/kg SC QW cohort and 4.2 months (range, 0.7-13.7) for the 0.8 mg/kg SC Q2W cohort.

Study Design/Methods

• Patients received TALVEY at a dose of 0.0005-0.18 mg/kg intravenously (IV) QW or Q2W, at the first RP2D of 0.405 mg/kg SC QW, or at the second RP2D of 0.8 mg/kg SC Q2W.
• Additional IV and SC doses were evaluated in order to determine the RP2Ds.

Safety Results

• The median time to onset of nail toxicities (relative to the first dose) was 50.5 days (range, 6-316), and the median event duration of nail toxicities was 74 days (range, 15247).⁵
• Nail-related AEs are summarized in Table: MonumenTAL-1 (Phase 1) Study: Nail-Related AEs.

MonumenTAL-1 Study Part 3 - Description and Management of Nail Toxicities

• Nail dysfunction, including brittle nails, cracking nails, painful nails, and loss of nails on both hands and feet, has been reported in multiple patients and are often a late manifestation (beyond cycle 1).¹⁰
• Per study protocol, symptomatic management with nail soaks, topical moisturizers, and topical steroids was recommended.¹⁰
• Nail complications that persist were evaluated by a dermatologic consult.¹⁰

CLINICAL DATA - Monumental-2 study

MonumenTAL-2 (MMY1004; clinicaltrials.gov identifier NCT05050097) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with MM.^6,17-19

Study Design/Methods

• Key eligibility criteria:
  • Cohort D: measurable MM, NDMM, ECOG PS of 0-1, and transplant ineligible or not intended for transplant.^17,18
  • Cohort E: measurable MM, ≥2 prior LOTs, including a PI and an immunomodulatory drug, ECOG PS of 0-1, prior pomalidomide and prior TCR (CAR-T and BsAb) permitted, and no prior GPRC5D-targeted therapy.^17,19
• Primary endpoint for Cohort D and Cohort E: safety; AEs assessed per CTCAE v5.0, except for CRS and immune effector cell-associated neurotoxicity syndrome, which were graded per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.^17-19

Cohort D

Nooka et al (2024)¹⁸ presented the incidence of nail-related AEs of the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 13.2 months (range, 10.0-14.6) and the TALVEY 0.8 mg/kg Q4W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 5.8 months (range, 1.7 [denotes patients who died]-12.0).

Safety Results

• Nail-related treatment-emergent adverse events (TEAE) are summarized in Table: MonumenTAL-2 Study (Cohort D): Summary of Nail-Related TEAEs.
• No treatment discontinuations were reported due to nail-related TEAEs.

Cohort E

Searle et al (2024)¹⁹ presented the incidence of nail-related AEs in the TALVEY + pomalidomide cohort from the MonumenTAL-2 study at a median follow-up of 16.8 months (range, 1.2-25.1).

Safety Results

• Nail-related AEs are summarized in Table: MonumenTAL-2 (Cohort E) Study: Nail-Related AEs.

CLINICAL DATA - REDIRECTT-1 STUDY - TALVEY + TECVAYLI COHORT

RedirecTT-1 (MMY1003; clinicaltrials.gov identifier: NCT04586426) is an ongoing, open-label, phase 1b/2 study evaluating the safety and effectiveness of the combination of TALVEY and TECAVYLI in patients with RRMM.^3,7,9,20

Study Design/Methods

• Key inclusion criteria: relapsed or refractory or intolerant to established therapies including the last LOT; prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.^7,20
• Primary endpoints: dose limiting toxicity and ORR.^7,20

Cohen et al (2025)^7,42 published the incidence of nail-related AEs from the phase 1 dose-escalation segment of the RedirecTT-1 study in the all-dose-level cohort at a median follow-up of 20.3 months (range, 0.5-37.1) and in the RP2R cohort at 18.2 months.

Safety Results

• At a data cutoff of March 15, 2024, the incidence of nail-related AEs was reported. See Table: RedirecTT-1 Study: Nail-Related AEs for additional details.

Clinical Data - TRIMM-2 Study

TRIMM-2 (MMY1002; clinicaltrials.gov identifier: NCT04108195) is an ongoing, phase 1b, 2-part, multicohort, open-label study evaluating DARZALEX FASPRO in combination with bispecific TCR antibodies with or without pomalidomide in patients with RRMM.^2,8,21

Study Design/Methods

• Key eligibility criteria²:
  • Double refractory to a PI and an immunomodulatory drug or received ≥3 prior lines of treatment (including a PI and an immunomodulatory drug).
  • Treatment with an anti-CD38 monoclonal antibody (>90 days prior allowed) including anti-CD38 refractory patients.
  • Prior BsAb and CAR-T were allowed.
• Key primary endpoints²:
  • Part 1: identify the RP2D for each treatment combination.
  • Part 2: safety and tolerability at the selected RP2D of each treatment combination.
  • Antitumor activity.

Bahlis et al (2024)²¹ presented the incidence of nail-related AEs the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohorts at a median follow-up of 15.8 months (range, 3.2-37.9) and 17.5 months (range, 0.2-37.7), respectively.

Safety Results

• Nail-related AEs are summarized in Table: TRIMM 2 (TALVEY + DARZALEX FASPRO + Pomalidomide Cohort) Study: Nail-Related Events.
• No treatment discontinuation was reported due to nail-related AEs.

Dholaria et al (2023)² presented the incidence of nail-related AEs in the TRIMM-2 study for the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO 1800 mg Q4W cohort at a median follow- up of 16.8 months (range, 1.9-31.0) and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO 1800 mg Q4W cohort at a median follow-up of 15.0 months (range, 1.0-23.3).

Safety Results

• Nail-related AEs are summarized in Table: TRIMM 2 (TALVEY + DARZALEX FASPRO Cohort) Study: Nail-Related Events.

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 19 February 2025.