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.^1-3
• The permitted and prohibited medications 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 below¹:

• 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^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).

MonumenTAL-1 Study Protocol - Permitted Medications

Patients are to receive full supportive care during the study.The following are examples of supportive therapies that may be used during the study³:

• Standard supportive care therapies (antiemetics, antidiarrheals, anticholinergics, antispasmodics, antipyretics, antihistamines, analgesics, antibiotics and other antimicrobials, histamine receptor antagonists or proton pump inhibitors and other medications intended to treat symptoms or signs of disease) as clinically indicated, according to institutional standards and as deemed necessary by the investigator.
• Bisphosphonates are permitted as part of supportive care. Patients who are currently using bisphosphonate therapy when they enter the study should continue the same treatment. If clinically indicated, patients may initiate bisphosphonate therapy as soon as possible during screening and no later than the end of cycle 1. After cycle 1, investigators should not prescribe bisphosphonates to patients who have not received it before, unless it has been discussed with the sponsor and there is no sign of disease progression. The use of bisphosphonates should then continue throughout the treatment phase until disease progression is established. In the case of severe adverse events such as hypercalcemia, bisphosphonates may be administered as clinically indicated, according to institutional standards, and as deemed necessary by the investigator.
• Growth factor support, erythropoietin-stimulating agents, platelet-stimulating factor and transfusions are permitted to treat symptoms or signs of neutropenia, anemia, or thrombocytopenia according to local standards of care.
• Infectious complications should be treated with oral, or intravenous (IV) antibiotics or other anti-infective agents as considered appropriate by the treating investigator for a given infectious condition, according to standard institutional practice.  

MonumenTAL-1 Study Protocol - Prohibited Medications

The following medications were prohibited during the study³:

• Any chemotherapy, anticancer immunotherapy (other than TALVEY), experimental therapy, or radiotherapy (except as noted below).
• Continuation of the study drug after emergency orthopedic surgery or radiotherapy is allowed only in the absence of disease progression and after consultation with and approval by the sponsor. For patients for whom delay of systemic therapy is not appropriate, emergency radiotherapy may consist of localized radiotherapy for pain control or for stabilization of an extensive bone lesion at high risk of pathologic fracture or damage to surrounding tissues. The circumstances must be reviewed by the sponsor to determine whether the study drug may be continued.
• Corticosteroids in excess of 10 mg daily of prednisone (or equivalent) for more than 14 days are prohibited, other than for the management of adverse events where no other treatment options are available and in consultation with the sponsor. Dexamethasone should not be administered as a pretreatment medication after cycle 1 day 1, except for patients who experience grade ≥2 CRS or infusion-related reactions. Nonsteroidal anti-inflammatory agents should be avoided to minimize the risk of exacerbation of potential sub-clinical myeloma-related kidney disease.
• Other immunosuppressant agents unless used as protocol-specified pretreatment medications or to treat an adverse event (eg, CRS).
• The use of IV contrast infusions should be avoided to prevent myeloma-related kidney disease. If administration of IV contrast is necessary, then adequate precautions including hydration are indicated.
• Routine transfusions should not be given on study drug administration days.
• The use of transdermal patches at the injection site must be avoided.
• Cytochrome P450 (CYP) substrates with a narrow therapeutic index should be used with caution during the first 48 hours after the first dose of TALVEY administration and during any events of CRS.
• For patients receiving warfarin, investigators should consider switching from warfarin to a different anticoagulant. For patients who cannot switch to a different anticoagulant and who experience CRS, coagulation parameters should be monitored closely during a CRS event and until CRS symptoms resolve.
• Live, attenuated vaccine(s) administered within 4 weeks/or as recommended by the product manufacturer prior to the first dose of TALVEY, during treatment, and for 100 days after the last dose of study drug (annual inactivated influenza vaccines are allowed).

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 26 July 2024.