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, including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody.^1-4
  • Schinke et al (2023)⁵ reported patient-reported outcomes (PROs) from the MonumenTAL-1 study, focusing on data through cycle 21 for the TALVEY 0.4 mg/kg weekly (QW) cohort and cycle 15 for the TALVEY 0.8 mg/kg every other week (Q2W) cohort. A meaningful improvement from baseline was observed in multiple myeloma (MM) symptoms, physical function, and overall health-related quality of life in the TALVEY 0.4 mg/kg QW and 0.8 mg/kg Q2W cohorts.
• Faiman et al (2024)⁶ presented the real-world experience of patients receiving TALVEY as well as physician perspectives regarding TALVEY treatment. Patients reported a high overall satisfaction. Symptoms did not limit treatment or cause missed doses. Patients found the symptoms bearable and noted that the treatment was effective at controlling the disease.

ClinIcal data

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^7,8

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.

Study Design/Methods (Phase 2)

Patients were enrolled into 1 of the following 3 cohorts^1,9:

• T-cell receptor (TCR) naïve: 0.4 mg/kg subcutaneous (SC) QW, not previously exposed to TCR such as chimeric antigen receptor-T-cell (CAR-T) therapy 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):
  • Measurable MM.⁹
  • ≥3 prior lines of therapy including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.⁹
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.⁹
• 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 class 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
• 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 (2023)⁵ reported PROs from the MonumenTAL-1 study, focusing on data through cycle 21 for the TALVEY 0.4 mg/kg QW cohort and from cycle 15 for the TALVEY 0.8 mg/kg Q2W cohort of the MonumenTAL-1 study.

Study Design/Methods

• This study included patients with triple-class-exposed RRMM who received RP2Ds of TALVEY (0.4 mg/kg QW cohort; 0.8 mg/kg Q2W cohort).
• PRO assessments included the following instruments for scoring:
  • European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Global health status [GHS], functioning, and symptoms, with a score range of 0 to 100. Higher scores indicate better GHS and functioning, higher scores for symptoms indicate worse severity, and a 10-point change from baseline indicates meaningful change.
  • EuroQol 5-Dimension 5-Level (EQ-5D-5L) visual analogue scale (VAS): patient health rated from 0 (worst) to 100 (best).
  • Patient Global Impression of Severity (PGIS): severity of disease.

Results

• As of January 17, 2023, phase 2 data were available for 122 and 109 patients who received ≥1 dose of TALVEY in the 0.4 mg/kg QW and 0.8 mg/kg Q2W cohorts, respectively. See Table: MonumenTAL-1 Study: Patient-Reported Outcomes for additional details.
• Compliance for EORTC QLQ-C30 completion was >97% at baseline and >80% at most posttreatment visits in the TALVEY 0.4 mg/kg QW and 0.8 mg/kg Q2W cohorts.
• The median time to improvement from baseline in most EORTC QLQ-C30 subscales and in the EQ-5D-5L VAS score was approximately 2 months in the TALVEY 0.4 mg/kg QW and 0.8 mg/kg Q2W cohorts. The median time to first worsening was 2 to ~9 months in these cohorts.

real-world study

Faiman et al (2024)⁶ reported the real-world experience of patients receiving TALVEY as well as physician perspectives regarding TALVEY treatment.

Study Design/Methods

• This qualitative study involved adults with MM from the United States (US) and physicians who had experience with TALVEY. These patients received TALVEY for at least 4 months.
• The overall study design was approved by both Johnson & Johnson’s Methods Review Board and the Sterling institutional review board (IRB).

Phase 1

• Patients were recruited through the HealthTree Cure Hub Registry, a platform sponsored by HealthTree that enables patients to voluntarily share their health information.
• A 2-hour virtual interview was conducted to discuss patients' experiences 1 to 2 months before and 4 to 5 months after starting TALVEY, focusing on GPRC5D-related symptoms, overall treatment impact, and satisfaction. The interviews took place from February 2024 to April 2024.

Phase 2

• In May 2024, patients and physicians met at a 2.5-hour, facilitated roundtable in Chicago, IL, to review phase 1 findings and generate ideas for symptom management.

Results

• Patient characteristics are shown in Table: Patient Characteristics.

Overall Satisfaction With TALVEY

• Patients reported a high overall satisfaction, with 75% of patients rating their satisfaction an 8 or higher on a 10-point scale. See Table: Patient Satisfaction With TALVEY Treatment on a 10-Point Scale.

Patient Experience

• Symptoms did not limit treatment or cause missed doses. Patients found the symptoms bearable and noted that the treatment was effective at controlling the disease. See Table: Patient Experience With Oral Symptoms.
• Oral symptoms, such as distorted taste/loss of taste and dry mouth, were common with varying severity.
• Ten patients reported weight loss; 92% of patients maintained adequate nutrition.
• Skin and nail symptoms were common; 83% of patients reported them having a mild impact on their quality of life.

Improvements in Quality of Life

• Ratings largely stayed consistent from 1 to 2 months before starting TALVEY to 4 to 5 months after starting TALVEY; however, improvement was noted more often than decline in several main areas. Physicians affirmed these findings as consistent with their observations. See Table: Improvements in Quality of Life.

Symptom Management

• Participant- and physician-suggested symptom management strategies are presented in Table: Physician and Patient Suggestions for Symptom Management Strategies.

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 December 2024.