SUMMARY

• MonumenTAL-1 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-cluster of differentiation 38 (CD38) monoclonal antibody.^1,2
  • Key inclusion and exclusion criteria in the MonumenTAL-1 study protocol are summarized below.³

CLINICAL DATA – Monumental-1 study

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^4,5 

The study was conducted in 3 parts; the primary objectives are listed below.¹

• Part 1 (phase 1; dose escalation): to characterize the safety of TALVEY and determine the recommended phase 2 doses (RP2D) 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 a summary of the study design for the phase 2 portion (part 3) of the study.

Study Design/Methods (Phase 2, Part 3)

Patients were enrolled into 1 of the following 3 cohorts^1,6:

• T-cell redirection (TCR) 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 anti-B-cell maturation antigen [BCMA] antibody-drug conjugate [ADC] allowed).
• TCR naive: 0.8 mg/kg SC 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 Inclusion Criteria (Part 3)
  • ≥18 years of age.³
  • Documented initial diagnosis of multiple myeloma (MM) per International Myeloma Working Group (IMWG) criteria.³
  • Measurable disease: MM must be measurable by central laboratory assessment³:
    • Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
    • Light chain MM without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
    • If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%.
  • Prior treatment³:
    • TCR naive cohorts: ≥3 prior lines of therapy that included at least one PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, and not previously exposed to TCR therapies.
    • Prior TCR cohort: ≥3 prior lines of therapy that included at least one PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, and have been previously exposed to TCR therapies.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.³
  • Hematology and chemistry parameters at screening are presented in Table: Clinical Laboratory Values at Screening.³

• Key Exclusion Criteria (Part 3)
  • Prior grade 3 or higher cytokine release syndrome (CRS; per Lee Criteria 2014⁷) related to any TCR or any prior G protein-coupled receptor family C group 5 member D (GPRC5D) targeting therapy.³
  • Prior antitumor therapy as follows, prior to the first dose of the study drug³:
    • Gene-modified adoptive cell therapy (e.g., CAR-T, natural killer [NK] cells) within 3 months.
    • Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less.
    • Monoclonal antibody treatment for MM within 21 days.
    • Cytotoxic therapy within 21 days.
    • Proteasome inhibitor therapy within 14 days.
    • Immunomodulatory agent therapy within 7 days.
    • Radiotherapy within 14 days. However, if palliative focal radiation is used, the patient is eligible irrespective of the end date of radiotherapy.
    • TCR naive cohorts: exposed to a CAR-T or TCR therapy at any time.
    • Prior TCR cohort: TCR therapy within 3 months.
  • Vaccinated with live, attenuated vaccine within 4 weeks or as recommended by the product manufacturer prior to the first dose, during treatment, or within 100 days of the last dose of TALVEY.³
  • Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.³
  • Received a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication).³
  • Received either of the following³:
    • An allogenic stem cell transplant within 6 months before the first dose of the study drug. Patients who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft versus host disease.
    • An autologous stem cell transplant ≤12 weeks before first dose of study drug.
  • Central nervous system involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging and lumbar cytology are required.³
  • Plasma cell leukemia (>2.0 x 10⁹/L plasma cells by standard differential), Waldenström’s macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome, or primary amyloid light chain amyloidosis.³
  • Any serious underlying medical condition, such as³:
    • Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection.
    • Active autoimmune disease or a documented history of autoimmune disease, with the exception of vitiligo, resolved childhood atopic dermatitis, and prior Grave’s disease that is currently euthyroid based on clinical symptoms and laboratory testing.
    • Psychiatric conditions (e.g., alcohol or drug abuse), severe dementia, or altered mental status.

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 20 June 2025.