SUMMARY

• Janssen does not recommend any practices, procedures, or usage that deviates from the product labeling or is not approved by the regulatory agencies.
• 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.^1-3
  • Rasche et al (2024)⁴ 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 subcutaneous (SC) weekly (QW) cohort, 23.4 months for the 0.8 mg/kg SC once every other week (Q2W) cohort, and 20.5 months for the prior T-cell redirection (TCR) therapy-exposed cohort. The overall response rate (ORR) in the extramedullary plasmacytoma (≥1) subgroup was 48.5%, 41.5%, and 44.0% for the 0.4 mg/kg SC QW, 0.8 mg/kg SC Q2W, and prior TCR therapy-exposed cohorts, respectively.
  • Krishnan et al (2023)⁵ presented subgroup analyses of the efficacy and safety results from the MonumenTAL-1 study phases 1/2 in patients who received TALVEY at the recommended phase 2 doses (RP2Ds) of 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W, including those who were naïve or exposed to TCR therapy. At a median follow-up of 18.4 months for the 0.4 mg/kg SC QW extramedullary disease (EMD) subgroup, the ORR was 48.5%. At a median follow-up of 12.1 months for the 0.8 mg/kg SC Q2W EMD subgroup, the ORR was 43.2%.
• 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). Cohort E is evaluating the safety and efficacy of TALVEY in combination with pomalidomide in 35 patients with RRMM.^6,7 Janssen does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
  • Searle et al (2024)⁷ presented the updated safety and efficacy results of TALVEY in combination with pomalidomide from the MonumenTAL-2 study. Following step-up dosing, patients received TALVEY + pomalidomide daily at a median follow-up of 16.8 months (range, 1.2-25.1). A total of 14.3% of patients had EMD, which was defined as the presence of ≥1 extramedullary plasmacytoma.
• 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.^8-10 Janssen does not recommend the use of TALVEY or TECVAYLI in a manner that is inconsistent with the approved labeling.
  • Cohen et al (2024)¹⁰ presented the updated efficacy and safety results in the evaluated cohorts, including in patients with EMD, at a median follow-up of 18.7 months (range, 0.5-33.8 [0.5 denotes patients who died]) for dose level 1-4 cohort and 13.6 months (range, 0.7-25.9)  for the TALVEY and TECVAYLI recommended phase 2 regimen (RP2R) cohort.
• Other relevant literature has been identified in addition to the data summarized above.¹¹

PRODUCT LABELING

• TECVAYLI (teclistamab-cry) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.;  https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf.
• TALVEY (talquetamab-TVs) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-pi.pdf.

CLINICAL DATA - mONUMENTAL-1 STUDY

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^12,13

The study was conducted in 3 parts; the primary objectives are listed below²:

• 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^2,14:

• TCR naïve: 0.4 mg/kg 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 type of TCR (CAR-T, BsAbs or CAR-T and BsAbs).
• Key eligibility criteria (Part 3; Phase 2):
  • Measurable MM.¹⁴
  • ≥3 prior lines of therapy 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 2014¹⁵) 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: ORR.²
• Key secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival, safety, immunogenicity, and pharmacodynamics.²
• 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
  • Step-up dosing 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.
  • Step-up dosing 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

Rasche et al (2024)⁴ presented longer term follow-up efficacy and safety results in patients receiving TALVEY in the MonumenTAL-1 study. The efficacy results of the latest follow-up are summarized below.

Results

Patient Characteristics

• A total of 143 patients were included in the 0.4 mg/kg SC QW cohort, 154 patients in the 0.8 mg/kg SC Q2W cohort, and 78 patients in the prior TCR-exposed cohort.
• The median duration of follow-up was 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.

Efficacy

• At a data cutoff of January 29, 2024, ORR was 74.1%, 69.5%, and 66.7% in the QW (n=143), Q2W (n=154), and prior TCR (n=78) cohorts, respectively. ORR in the EMD plasmacytoma subgroup is detailed in Table: MonumenTAL-1 Study: ORR in the EMD Plasmacytomas Subgroup.

Krishnan et al (2023)⁵ evaluated the efficacy and safety of TALVEY in key high-risk and BCMA-exposed subgroups of patients from phases 1/2 of the MonumenTAL-1 study.

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

• 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 analysis. Baseline demographic characteristics in the 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W cohorts across the EMD subgroup is presented in Table: MonumenTAL-1 Study: Baseline Demographic Characteristics in EMD Subgroup.

Efficacy

EMD Subgroup

• The median follow-up and ORR in the EMD subgroup of the 0.4 mg/kg QW and 0.8 mg/kg Q2W dosing cohorts is presented in Table: MonumenTAL-1 Study: ORR in EMD Subgroup.
• Select efficacy outcomes in the EMD subgroup in the 0.8 mg/kg SC Q2W cohort are summarized in Table: MonumenTAL-1 Study: Efficacy Outcomes in the EMD Subgroup in the 0.8 mg/kg SC Q2W Cohort.

Safety

• Adverse events (AEs) observed in the RP2Ds of the 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W EMD subgroup are summarized in Table: MonumenTAL-1 Study: Summary of AEs in the EMD Subgroup.
  • Rates of AEs (dysgeusia, nail AEs, and skin AEs) were lower in EMD subgroup in the 0.4 mg/kg SC QW cohort.
  • Rates of infection were lower in the EMD subgroup in both cohorts.

CLINICAL DATA - Monumental-2 study (Cohort e)

MonumenTAL-2 (MMY1004; clinicaltrials.gov identifier NCT05050097) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination other anticancer therapies in patients with MM.^6,7,16

Cohort E of the MonumenTAL-2 study is evaluating the efficacy and safety of TALVEY in combination with pomalidomide in 35 patients with RRMM.^6,7,16

Study Design/Methods

• Key eligibility criteria:
  • Measurable MM.¹⁶
  • At least 2 prior lines of treatment, including a PI and an immunomodulatory drug.¹⁶
  • ECOG PS of 0-1.¹⁶
  • Prior pomalidomide and prior TCR (CAR-T and BsAb) permitted.¹⁶
  • No prior GPRC5D-targeted therapy.¹⁶
• Primary endpoint: Safety and AEs were assessed per Common Terminology Criteria for Adverse Events (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
• Key secondary endpoints: ORR (assessed per International Myeloma Working Group [IMWG] 2016 criteria), time to response, DOR, and PFS.¹⁶
• Dosing¹⁶:
  • TALVEY: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W (following step-up dosing).
  • Pomalidomide: 2 mg by mouth (PO) daily, with dose escalation to 4 mg PO daily permitted (starting at cycle 2).

Searle et al (2024)⁷ presented the updated safety and efficacy 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), which are summarized below.

Results

Patient Characteristics

• A total of 16 patients were included in the 0.4 mg/kg QW + pomalidomide cohort and 19 patients in the 0.8 mg/kg Q2W + pomalidomide cohort.¹⁶
• Overall, the median age was 65.0 years. Of note, 14.3% of patients (12.5% [n=2] in the TALVEY 0.4 mg/kg QW + pomalidomide cohort; 15.8% [n=3] in the TALVEY 0.4 mg/kg QW + pomalidomide cohort) had EMD, which was defined as the presence of ≥1 extramedullary plasmacytoma.¹⁶

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 + TECVAYLI in patients with RRMM.^8-10

Study Design/Methods

• Key inclusion criteria: relapsed or refractory or intolerant to established therapies including the last line of therapy, prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.¹⁰
• Primary endpoints: safety, identify RP2D(s), and schedule.¹⁰
• Dosing: eligible patients received varying dose levels of TALVEY and TECVAYLI to determine the RP2R dose and schedule of the combination.¹⁰
  • All dose levels: Five varying dose levels of TALVEY and TECVAYLI.¹⁰
  • RP2R: TALVEY 0.8 mg/kg SC Q2W and TECVAYLI 3.0 mg/kg SC Q2W.¹⁰

Cohen et al (2024)¹⁰ presented the updated efficacy and safety results for the all dose levels cohort and the TALVEY and TECVAYLI RP2R cohort in the RedirecTT-1 study, including in patients with EMD.

Baseline Characteristics

• At a data cutoff date of March 15, 2024, 94 patients were included in the all dose-level cohorts, and 44 patients were included in the RP2R cohort.
• EMD was defined as ≥1 nonradiated, bone-independent lesion measuring ≥2 cm. Patients with paraskeletal plasmacytomas were permitted but not counted as EMD.
  • EMD was present in 36.2% of patients (n=34), and 40.9% of patients (n=18) in the all dose-level and RP2R cohorts, respectively.

Efficacy

• Efficacy outcomes in the EMD subgroup were reported in dose level 1-4 and RP2R cohorts. See Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Response Summary in Patients With EMD.

Literature Search

A literature search of Ovid MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 18 November 2024.