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.
• Cytokine release syndrome (CRS) has been reported as an adverse event (AE) in the MonumenTAL-1 study.^1-3
• 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.^1,3-6
  • Morillo et al (2024)⁷ presented the impact of fewer step-up doses (SUDs) of TALVEY (0.8 mg/kg every other week [Q2W]) on the efficacy, safety, and CRS parameters in alternative TALVEY Q2W SUD (n=6, group 1; n=12, group 2) and global (N=154) Q2W TALVEY cohorts. The overall response rate (ORR) was 83.3% in both alternative TALVEY Q2W SUD cohorts and 69.5% in the global TALVEY Q2W cohort. CRS was reported in 100% and 91.7% of patients in group 1 and group 2 of the alternative TALVEY Q2W SUD cohort, respectively.

CLINICAL DATA - Monumental-1 Study

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^5,6 The study was conducted in 3 parts; the primary objectives are listed below³:

• Part 1 (phase 1; dose escalation): to characterize the safety of TALVEY and determine the recommended phase 2 doses (RP2Ds) and dosing 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^3,8:

• T-cell redirection (TCR)-naïve: 0.4 mg/kg subcutaneous (SC) weekly (QW), not previously exposed to TCR therapies such as chimeric antigen receptor-modified T-cell (CAR-T) therapy or bispecific antibodies (prior exposure to B-cell maturation antigen [BCMA] antibody-drug conjugate [ADC] allowed).
• TCR-naïve: 0.8 mg/kg SC Q2W, not previously exposed to TCRs (prior exposure to 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.⁸
  • ≥3 prior lines of therapy including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.⁸
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.⁸
• Primary endpoint: ORR.³
• Key secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival, safety, immunogenicity, and pharmacodynamics.³
• 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.⁴
  • SUD schedule for 0.4 mg/kg SC QW⁴:
    • Week 1: SUDs 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.
  • SUD schedule for 0.8 mg/kg SC Q2W⁴:
    • Week 1: SUDs 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 SUD and for the first full treatment dose of TALVEY.⁴
  • Patients were required to be hospitalized for at least 48 hours from the start of the injection for each SUD and the first full treatment dose of TALVEY.⁴

Morillo et al (2024)⁷ presented the impact of fewer SUDs on efficacy and safety, including CRS parameters, in the alternative TALVEY Q2W SUD and global TALVEY 0.8 mg/kg Q2W cohorts.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• In MonumenTAL-1, alternative SUD groups were added to the 0.8 mg/kg Q2W schedule.
• A total of 18 patients were included in this analysis to evaluate alternative TALVEY Q2W SUD regimens.
  • Group 1 (n=6): week 1 SUD of TALVEY (0.03 mg/kg and 0.2 mg/kg SC); cycle 1, day 1 of TALVEY (0.8 mg/kg SC Q2W).^4,7
  • Group 2 (n=12): week 1 SUD of TALVEY (0.06 mg/kg and 0.4 mg/kg SC); cycle 1, day 1 of TALVEY (0.8 mg/kg SC Q2W).^4,7
  • Patients in both Group 1 and 2 could switch to 0.8 mg/kg Q4W at confirmed partial response or better (≥PR).
• The median duration of follow-up was 6.7 months (range, 2.2-9.9).
• Most patients had high-risk cytogenetics (10/18) and were triple-class refractory (11/18), being refractory to the last line of therapy (11/18). Three patients had extramedullary plasmacytomas.

Efficacy

• As of July 31, 2024, ORR was 83.3% in each group of the alternative TALVEY Q2W SUD cohort. See Table: MonumenTAL-1 Study: Summary of Efficacy Response in Alternative TALVEY Q2W SUD and Global TALVEY Q2W Cohorts.

Safety

CRS Incidence, Severity, Timing, and Treatment

• CRS was reported in 100% of patients (n=6) in group 1 and in 91.7% of patients (n=11) in group 2 of the alternative TALVEY Q2W SUD cohort.
• Summary of CRS events in the alternative SUD and global TALVEY Q2W cohorts is presented in the Table: MonumenTAL-1 Study: Summary of CRS Events in Alternative TALVEY Q2W SUD and Global TALVEY Q2W Cohorts.
  • At a median follow-up of 23.4 months (range, 0.2-37.4), the rates of grade 1 and 3 CRS events were consistent between the alternative TALVEY Q2W SUD and global TALVEY Q2W cohorts.
  • The rate of grade 2 events was higher in the alternative TALVEY Q2W SUD cohort. See Table: MonumenTAL-1 Study: CRS Incidence and Severity in Alternative TALVEY Q2W SUD and Global TALVEY Q2W Cohorts.
• Incidence of CRS in the SUD phase in all 3 cohorts are presented in Table: MonumenTAL-1 Study: CRS Timing in Alternative TALVEY Q2W SUD and Global TALVEY Q2W Cohorts.
• Tocilizumab was administered for CRS in 77.8% of patients in the alternative TALVEY Q2W SUD cohort and in 37.0% of patients in the global TALVEY Q2W cohort. Patients who received tocilizumab did not experience any subsequent grade 2 event.
• During administration of the first SUD, 1 patient (8.3%) in group 2 experienced grade 1 neurotoxicity concurrent with CRS, which resolved without leading to TALVEY discontinuation.
• None of the patients in the alternative TALVEY Q2W SUD cohorts discontinued TALVEY due to CRS; however, 1 patient in the global TALVEY Q2W cohort discontinued TALVEY due to CRS.

Treatment Discontinuation due to other TEAEs

• No TALVEY discontinuations or deaths due to treatment-emergent adverse events (TEAEs) were reported in the alternative TALVEY Q2W SUD cohort.

Pharmacokinetics

• As per the preliminary analysis from cycle 1 day 1 onward, talquetamab serum exposure was similar between the alternative TALVEY Q2W SUD and the global TALVEY Q2W cohorts.
• In group 1 and group 2, the median number of treatment cycles received was 10.0 (range, 4-11) and 5.0 (range, 2-10), respectively.

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 29 October 2024.