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.
• Administration-related reactions (ARRs) have been reported as an adverse event (AE) in the MonumenTAL-1 study.¹
• 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
  • Chari et al (2022)¹ published the safety and efficacy results of TALVEY in the phase 1 portion of the MonumenTAL-1 study.
  • Per study protocol, patients were required to be managed for occurrence of systemic ARRs during therapy with TALVEY.³
  • Purcell et al (2023)⁴ presented the nursing experience on the management of injection site reactions from a single center in the phase 1/2 MonumenTAL-1 study.

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 below²:

• Part 1 (phase 1; dose escalation): to characterize the safety of TALVEY and determine the recommended phase 2 dose (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^2,7:

• T-cell redirection (TCR) therapy naive: 0.4 mg/kg subcutaneous (SC) weekly (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 naive: 0.8 mg/kg SC once every other week (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 multiple myeloma (MM).⁷
  • ≥3 prior lines of therapy including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.⁷
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.⁷
• Primary endpoint: overall response rate (ORR).²
• Key secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival, safety, immunogenicity, and pharmacodynamics.²

Chari et al (2022)¹ published the safety and efficacy results from the phase 1 portion of the MonumenTAL-1 study. Results specific to ARRs 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

• Injection site reactions (grade 1 or 2) were reported in 20% and 7% of patients in the 0.405 mg/kg SC QW and 0.8 mg/kg SC Q2W cohorts, respectively.

MonumenTAL-1 Protocol (Part 3) - Management of Administration-Related Reactions³

• Per study protocol, patients are required to be managed for occurrence of ARRs during therapy with TALVEY for both IV and SC administration; however, for the purpose of this summary, management guidelines only for SC administration have been described below.
• ARR events may include wheezing, flushing, hypoxemia, fever, chills, rigors, bronchospasm, headache, rash, pruritus, arthralgia, hypo- or hypertension, etc. Institutional guidelines must be followed for managing anaphylactic reactions.
• Trained clinical personnel should be prepared to intervene in the event of ARRs. Resources necessary for resuscitation (ie, agents such as epinephrine and aerosolized bronchodilator; medical equipment such as oxygen, tracheostomy equipment, and a defibrillator) should be readily available. Vital signs and laboratory parameters should be monitored at regular intervals until normalized.
• Guidelines for managing ARRs are summarized in the Table: Guidelines for the Management of ARRs in MonumenTAL-1.

Purcell et al (2023)⁴ presented the management of injection site reactions in 24 patients from a single center (Mount Sinai, New York) in phase 1/2 of the MonumenTAL-1 study.

Treatment Disposition

• Among the 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W cohorts, 24 patients received TALVEY. Of these, 8 patients received 0.4 mg/kg SC QW, and 16 patients received 0.8 mg/kg SC Q2W doses.
• The median duration of follow-up was 18.8 months for the 0.4 mg/kg SC QW cohort and 12.7 months for the 0.8 mg/kg SC Q2W cohort.

Management of Injection Site Reactions

• Loratadine 10 mg orally daily for 3–5 days post-TALVEY dose
• Triamcinolone 0.1% cream twice a day

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 09 September 2024.