SUMMARY

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• Skin toxicities have been reported as adverse events (AEs) in the MonumenTAL-1, MonumenTAL-2, TRIMM-2, and RedirecTT-1 studies.^1-6
• 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.^1,4,7-14
  • Schinke et al (2024)¹⁵ presented efficacy and safety results from a subgroup analysis in Black patients who 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). Skin- and rash-related AEs were reported in Black patients.
  • Rasche et al (2024)¹⁰ 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 T-cell redirection therapy (TCR)-exposed cohort. Skin- and rash-related AEs were reported in the QW, Q2W, and TCR cohorts.
  • Chari et al (2024)¹¹ published the clinical management of AEs in patients with RRMM treated with TALVEY in the MonumenTAL-1 study. Rash-related AEs and non-rash-related skin AEs were reported in the QW, Q2W, and TCR cohorts.
  • Jakubowiak et al (2023)¹² presented the updated efficacy and safety results 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, respectively. Skin- and rash-related AEs were reported in the overall prior TCR cohort.
  • Chari et al (2023)¹³ presented efficacy and safety results in patients from MonumenTAL-1 who switched to reduced or less frequent dosing with TALVEY. Skin-related toxicities reported in the Prospective Dose Intensity Reduction Cohorts at a median follow-up of 13.2 months are described below.
  • Krishnan et al (2023)¹⁴ evaluated the efficacy and safety of TALVEY in key high-risk and prior B-cell maturation antigen (BCMA) therapy subgroups of patients from the MonumenTAL-1 study. Skin-related AEs of the high-risk subgroups are described below.
  • Chari et al (2022)^4,5 published the safety and efficacy results of TALVEY 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). Skin- and rash-related AEs were reported in the QW and Q2W cohorts.
  • Per MonumenTAL-1 protocol, rashes appear to be a late manifestation (beyond 1 cycle) and should be managed as per institutional guidance. Rashes occurring during the first cycle should be treated with topical steroids and early consideration of a short course of oral steroids to reduce the risk of rash progression. Rashes that have not responded to treatment should be evaluated by a dermatologic consult.⁷
• 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).^6,16-18 Janssen does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
  • Cohort D is evaluating the efficacy and safety of TALVEY in combination with DARZALEX FASPRO^® and lenalidomide in 34 patients with newly diagnosed multiple myeloma (NDMM).
    • Nooka et al (2024)¹⁷ presented the initial efficacy and safety results of TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide at a median follow-up of 13.2 months (range, 10.0-14.6) and TALVEY 0.8 mg/kg every 4 weeks (Q4W) + DARZALEX FASPRO + lenalidomide at a median follow-up of 5.8 months (range, 1.7 [denotes patients who died]-12.0). Skin- and rash-related TEAEs were reported in both cohorts.
  • Cohort E is evaluating the safety and efficacy of TALVEY in combination with pomalidomide in 35 patients with RRMM.¹⁸
    • Searle et al (2024)¹⁸ presented the updated efficacy and safety 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). Skin- and rash-related AEs were reported.
• TRIMM-2 (MMY1002) is an ongoing, phase 1b, multicohort open-label study evaluating the efficacy and safety of DARZALEX FASPRO in combination with TECVAYLI^® or TALVEY with or without pomalidomide in patients with RRMM.^2,19,20 Janssen does not recommend the use of TECVAYLI, TALVEY, or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
  • Bahlis et al (2024)²⁰ presented the efficacy and safety results of the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide and 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. Skin-related AEs were reported in both TALVEY + DARZALEX FASPRO + pomalidomide cohorts.
  • Dholaria et al (2023)² presented the updated results 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. Skin-related AEs were reported in TALVEY + DARZALEX FASPRO cohorts.
• RedirecTT-1 (MMY1003) is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY and TECVAYLI in patients with RRMM.^3,21,22 Janssen does not recommend the use of TALVEY and TECVAYLI in a manner that is inconsistent with the approved labeling.
  • Cohen et al (2024)²² presented the updated efficacy and safety results in the evaluated cohorts, including in patients with extramedullary disease (EMD), at a median follow-up of 20.3 months for the all dose levels cohort and 18.2 months (range, 0.7-27.0) for the TALVEY and TECVAYLI recommended phase 2 regimen (RP2R) cohort. Rash and non-rash skin AEs were reported in the all dose levels and RP2R cohorts.
• Other relevant literature has been identified in addition to the data summarized above:
  • Retrospective descriptive study reported skin toxicities.²³
  • Cases series and case reports reported skin toxicities.^24-27
  • Nursing and advance practice practitioner’s considerations for management of skin toxicities.^28-31
  • Real-world evidence describing and managing skin toxicities.³²

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.³³ 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.^34-36 It is also found to be expressed in plasma cells and hard, keratinized tissues, such as skin and nails. GPRC5D is variable in the skin and highest in keratin-expressing hair follicles.^37-39
• Phase 1 dose-escalation studies of GPRC5D-targeting BsAbs or CAR-T therapy have reported AEs related to skin toxicities and rash. Clinical symptoms indicative of skin toxicities that may be attributed to GPRC5D-targeting BsAbs may include but are not limited to maculopapular rash, dry skin, palmar-plantar erythrodysesthesia syndrome, pruritus, and alopecia.^37,39,40 Skin-related AEs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).⁴¹

CLINICAL DATA - Monumental-1 Study

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^8,9

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.

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 cohorts^1,12:

• TCR naïve: 0.4 mg/kg SC QW, not previously exposed to TCR such as CAR-T 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 type of TCR (CAR-T, BsAb or CAR-T and BsAb).
• Key eligibility criteria (Part 3; Phase 2):
  • Measurable MM.¹²
  • ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.¹²
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.¹²
• Key exclusion criteria (Part 3; Phase 2):
  • Prior grade 3 or higher cytokine release syndrome (CRS; per Lee criteria 2014⁴²) related to any TCR or any prior GPRC5D-targeting therapy.⁷
  • Received cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within 14 days prior to study drug (not including premedication).⁷
• 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
• 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.⁷
  • Step-up dosing for 0.4 mg/kg SC QW⁷:
    • 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.
  • Step-up dosing for 0.8 mg/kg SC Q2W⁷:
    • 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.⁷
  • 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.⁷

Schinke et al (2024)¹⁵ presented efficacy and safety results 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. Results specific to skin-related AEs are summarized below.

Results

Treatment Disposition

• Overall, 29 (10%) Black patients and 254 (86%) White patients from the MonumenTAL-1 study were assessed.
• The median follow-up was 26 months for the Black subgroup and 31 months for the White subgroup.

Safety

• Details of GPRC5D-associated skin-related AEs reported in both groups are summarized in Tables: MonumenTAL-1 Study: Summary of Skin- and Rash-Related AEs in Black vs White Patients and MonumenTAL-1 Study: Characterization of Skin- and Rash-Related AEs in Black vs White Patients.

Rasche et al (2024)¹⁰ presented longer-term follow-up efficacy and safety results 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. Results specific to skin- and rash-related AEs are summarized below.

Results

Safety

• Details on GPRC5D-associated skin- and rash-related AEs are summarized in Table: MonumenTAL-1 Study: GPRC5D-Associated Skin- and Rash-Related AEs.

Chari et al (2024)¹¹ published the clinical management of AEs in patients with RRMM treated with TALVEY in the MonumenTAL-1 study. Results specific to skin toxicities are summarized below.

Results

Safety

• In the MonumenTAL-1 study, rash-related AEs included rash, maculopapular rash, erythematous rash, and erythema. Non-rash-related AEs included rash, maculopapular rash, erythematous rash, and erythema.
• A summary of dermatologic AEs associated with TALVEY in MonumenTAL-1 is presented in Table: MonumenTAL-1 Study: Dermatologic AEs Associated With TALVEY.
• Across all events, patients experienced rash-related toxicity for a median total duration of 73 days (range, 6-610), and non-rash-related toxicity for a median of 196.5 days (range, 3-688).
• Most rash-related and non-rash-related AEs never reached grade 2, and a majority of them partially or completely resolved. Most skin toxicities were grade 1/2 in severity (grade 3 rash-related AEs, n=12 [3.5%]; grade 3 non-rash-related AE, n=1 [0.3%]) across the 3 cohorts.
• Few dose modifications occurred due to rash- and non-rash-related AEs.
• No patients discontinued treatment due to rash-related AEs. Three patients discontinued treatment due to non-rash-related AEs (2 patients due to skin exfoliation in the 0.4 mg/kg QW cohort and 1 patient due to dry skin in the 0.8 mg/kg Q2W cohort).

Supportive Measures/Management

• According to the MonumenTAL-1 protocol, rashes should be managed following institutional guidelines, with topical corticosteroids used for rashes in the first treatment cycle.
  • Early use of oral corticosteroids is advised to minimize the risk of rash progression.
  • Investigators used low-potency topical corticosteroids for skin toxicities, varying the potency based on the location and severity of the condition, per protocol recommendations.
  • Short pulses of oral corticosteroids should be considered for generalized rashes not controlled by topical corticosteroids and/or those affecting a large surface area.
• Management of skin toxicities should involve early intervention with liberal use of emollients (applied several times daily and especially after bathing) and adequate systemic hydration at the start of treatment (on and before development of symptoms) is crucial.
• Concomitant medications were also used to manage skin toxicities in all 3 cohorts. See Table: MonumenTAL-1 Study: Most Common Supportive Measures and Concomitant Treatments for Skin Toxicities.
• Investigator experience indicates that exfoliation mainly occurs on the palms and soles.
• Dermatological consultation may be considered for persistent or high-grade skin toxicities, particularly after cycle 2 or if rashes remain unresponsive to emollients or low-potency corticosteroids. This is essential if the treatment center, including its dermatology consultants, has limited experience with TALVEY.
• Photographic records may help in assessing skin toxicities over time.

Jakubowiak et al (2023)¹² presented the updated efficacy and safety results in patients with prior TCR, including an additional 19 patients enrolled in the MonumenTAL-1 study since the prior analysis. Results specific to skin toxicities are summarized below.

Results

Treatment Disposition

• A total of 70 patients with prior TCR were enrolled; 67 patients (95.7%) were exposed to BCMA-targeting TCR.
• The median follow-up was 18.4 months for the overall prior TCR cohort, 18.4 months for the prior CAR-T cohort, and 16.3 months for the prior BsAb cohorts.

Safety

• AEs related to skin toxicities are summarized in Table: MonumenTAL-1 Study: Skin-Related AEs (Prior TCR).

Chari et al (2023)¹³ presented efficacy and safety results in patients in MonumenTAL-1 who switched to reduced or less frequent dosing with TALVEY. Results specific to skin toxicities in Prospective Dose Intensity Reduction Cohorts are summarized below.

Study Design/Methods

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

Results

Treatment Disposition

• Overall, 19 patients were included in the Prospective Dose Intensity Reduction Cohorts.
• The median duration of follow-up for patients included in the Prospective Dose Intensity Reduction Cohorts was 13.2 months (range, 4.0±16.1).

Safety

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

Krishnan et al (2023)¹⁴ evaluated the efficacy and safety of TALVEY in key high-risk and prior BCMA therapy subgroups of patients from the phase 1/2 MonumenTAL-1 study. Results specific to skin toxicities are summarized below.

Results

Treatment Disposition

• Overall, 143 patients in the 0.4 mg/kg SC QW cohort and 145 patients in the 0.8 mg/kg SC Q2W cohort were included in the subgroup analyses.
  • Subgroups of patients with high-risk features included ≥75 years of age, high-risk cytogenetics (del(17p), t(4;14), and/or t(14;16)), International Staging System (ISS) stage III, renal impairment (baseline function ≤60 mL/min/1.73 m²), triple-class refractory (to a PI, immunomodulatory drug, and anti-CD38 monoclonal antibody), and extramedullary disease ≥1 (including soft tissue plasmacytomas).
  • Subgroups of patients with prior BCMA therapies included TCR-naïve BCMA ADC exposed in the 0.4 mg/kg SC QW TALVEY dose, TCR-naïve BCMA ADC exposed in the 0.8 mg/kg SC Q2W TALVEY dose, and TCR-exposed (includes BCMA ADC, BCMA CAR-T, and BCMA BsAb) QW and Q2W dosing.

Safety

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

Chari et al (2022)⁴ published the safety and efficacy results from the phase 1 portion of the MonumenTAL-1 study. Results specific to skin toxicities are summarized below.

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.

Results

Treatment Disposition

• Overall, 30 patients were included in the 0.405 mg/kg SC QW cohort and 44 patients in the 0.8 mg/kg SC Q2W cohort.
• The median duration of follow-up was 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.

Safety

• The median time to onset of rash toxicities was 21 days (range, 5-250) after the first SC doses, with 61.8% of events resolved at a median duration of 17 days (range, 2-350).⁵
• The median time to onset of skin toxicities relative to first SC dose was 24.0 days (range, 3-384), with 46% of skin toxicities resolved at a median event duration of 39 days (range, 1-218)⁵.
• Oral and topical glucocorticoids were used to treat grade 3 rashes. In the 0.8 mg/kg SC Q2W cohort (n=7), all but one patient with a grade 3 rash were able to resume treatment after resolution of the rash.⁴
• Skin-related AEs are summarized in Table: MonumenTAL-1 (Phase 1) Study: Skin-Related AEs.

MonumenTAL-1 Protocol (Part 3) - Description and Management of Skin Toxicities⁷

Rashes appear to be a late manifestation (beyond 1 cycle) and should be managed as per institutional guidance. Rashes occurring during the first cycle should be treated with topical steroids and early consideration of a short course of oral steroids to reduce the risk of rash progression. Rashes that have not responded to treatment should be evaluated by a dermatologic consult.

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.^6,16-18 Summarized below are the skin- and rash-related AEs in Cohorts D and Cohort E.

Study Design/Methods

• Key eligibility criteria:
  • Cohort D: measurable MM, NDMM, ECOG PS of 0-1, and transplant ineligible or not intended for transplant.^16,17
  • 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.^16,18
• 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.^16-18

Cohort D

Nooka et al (2024)¹⁷ presented the initial efficacy and safety results of the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide and TALVEY 0.8 mg/kg Q4W + DARZALEX FASPRO + lenalidomide cohorts from the MonumenTAL-2 study. Results specific to skin- and rash-related TEAEs are summarized below.

Results

Treatment Disposition

• A total of 8 patients were included in the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort and 26 patients were included in the TALVEY 0.8 mg/kg Q4W + DARZALEX FASPRO + lenalidomide cohort.
• The median follow-up was 13.2 months (range, 10.0-14.6) for the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort and 5.8 months (range, 1.7 [denotes patients who died]-12.0) for the TALVEY 0.8 mg/kg Q4W + DARZALEX FASPRO + lenalidomide cohort.

Safety

• Skin-related treatment-emergent adverse events (TEAEs) are summarized in Table: MonumenTAL-2 Study (Cohort D): Summary of Skin- and Rash-Related TEAEs.
• No treatment discontinuations were reported due to skin- or rash-related TEAEs.

Cohort E

Searle et al (2024)¹⁸ presented the updated efficacy and safety results of TALVEY in combination with pomalidomide from the MonumenTAL-2 study. Results specific to skin- and rash-related AEs are summarized below.

Results

Treatment Disposition

• Overall, 16 patients were included in the TALVEY 0.4 mg/kg QW + pomalidomide cohort and 19 patients were included in the TALVEY 0.8 mg/kg Q2W + pomalidomide cohort.
• The median follow-up was 16.8 months (range, 1.2-25.1).
• Prior treatments included the following: CAR-T (8.6%), BsAb (2.9%), anti-CD38 antibody (74.3%), and pomalidomide (22.9%).

Safety

• TEAEs related to skin toxicities are summarized in Table: MonumenTAL-2 (Cohort E) Study: Skin-Related AEs.

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.^2,19,20

Study Design/Methods

• Key eligibility criteria²:
  • Double refractory to a PI and an immunomodulatory drug or received ≥3 prior LOTs (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)²⁰ presented the efficacy and safety results of the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide and 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. Results specific to skin-related AEs are summarized below.

Study Design/Methods

• Dosing:
  • TALVEY: 2-3 SUDs before receiving the first full doses of either 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W.
    • The dose frequency could be reduced from QW to Q2W after cycle 4 if patients achieved PR and from Q2W to Q4W after cycle 8 if they achieved very good partial response (VGPR).
  • DARZALEX FASPRO 1800 mg SC: cycles 1-2, QW; cycles 3-6, Q2W; cycles 7+, Q4W.
  • Pomalidomide 2 mg PO: Starting cycle 2. The dosage may be lowered due to hematologic AEs.

Results

Treatment Disposition

• Overall, 18 patients were included in the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide cohort and 59 patients were included in the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohort.
• The median duration of follow-up was 15.8 months (range, 3.2-37.9) for the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide cohort and 17.5 months (range, 0.2-37.7) for the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohort.

Safety

• Skin-related AEs are summarized in Table: TRIMM-2 Study (TALVEY + DARZALEX FASPRO + Pomalidomide Cohort): Non-Rash Skin AEs.
• Rash (rash, maculopapular rash, erythematous rash, and erythema) was reported in 27.8% and 25.4% of patients in the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide and TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohorts, respectively.
• No treatment discontinuation was observed due to skin AEs.

Dholaria et al (2023)² presented the updated results of the TRIMM-2 study. Results specific to skin-related toxicities reported in patients receiving TALVEY + DARZALEX FASPRO are summarized below.

Study Design/Methods

• Dosing:
  • TALVEY: 1-3 SUDs within 1 week before receiving the full doses of either 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W.
    • The dose frequency of TALVEY could be reduced from QW to Q2W after 4 cycles if patients achieved PR and further from Q2W to Q4W after 8 cycles if they achieved VGPR.
  • DARZALEX FASPRO 1800 mg SC: cycles 1-2, QW; cycles 3-6, Q2W; cycles 7+, Q4W.

Results

Treatment Disposition

• Overall, 14 patients were included in the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO 1800 mg Q4W cohort and 51 patients in the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO 1800 mg Q4W cohort.
• The median duration of follow-up was 16.8 months (range, 1.9-31.0) for the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO 1800 mg Q4W cohort and 15.0 months (range, 1.0-23.3) for the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO 1800 mg Q4W cohort.

Safety

• Treatment discontinuation due to AEs occurred in 1.5% of patients (n=1). A patient discontinued due to toxic skin eruptions.
• Rashes were managed with topical corticosteroids or a short course of oral corticosteroids.
• Skin-related AEs are summarized in Table: TRIMM-2 Study (TALVEY + DARZALEX FASPRO Cohort): Skin-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 TECVAYLI in patients with RRMM.^3,21,22

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.²²
• Primary endpoints: safety, identify RP2R(s) and schedule.²²
• Dosing: eligible patients received varying dose levels of TALVEY and TECVAYLI to determine the RP2R dose and schedule of the combination.²²
  • All dose levels: Five varying dose levels of TALVEY and TECVAYLI.²²
  • RP2R: TALVEY 0.8 mg/kg SC Q2W and TECVAYLI 3.0 mg/kg SC Q2W.²²

Cohen et al (2024)²² presented the updated efficacy and safety results for the all dose levels cohort and the TALVEY and TECVAYLI RP2R cohort, including in patients with EMD. Results specific to skin-related AEs are summarized below.

Results

Treatment Disposition

• Overall, 94 patients were included in the all dose levels cohort and 44 patients were in the RP2R cohort.
• The median duration of follow-up was 20.3 months in the all dose levels cohort and 18.2 months (range, 0.7-27.0) in the RP2R cohort.

Safety

• Skin-related AEs are summarized in Table: RedirecTT-1 Study: Skin-related AEs.

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 02 January 2025.