SUMMARY  

• MajesTEC-1 (MMY1001) is an ongoing, phase 1/2 study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).^1,2
  • Cohort A (triple-class exposed) included 165 patients with RRMM who were triple-class exposed to a proteasome inhibitor (PI), an immunomodulatory drug and an anti-CD38 monoclonal antibody.¹ 
  • Cohort C included 40 patients with RRMM, previously treated with a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. All patients enrolled in Cohort C had prior exposure to B-cell maturation (BCMA)-targeted therapies. Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.³ 
• Prohibited medications in the MajesTEC-1 study are summarized below.^2,4

CLINICAL DATA - Majestec-1 study

MajesTEC-1 (MMY1001; clinicaltrials.gov identifiers: NCT03145181; NCT04557098) is evaluating the safety and efficacy results of TECVAYLI in patients with RRMM after ≥3 prior lines of therapy, including triple-class exposure to a proteasome inhibitor (PI), an immunomodulatory drug and an anti-CD38 monoclonal antibody.^1,2

Study Design/Methods

The main objectives are as follows: Part 1 (dose escalation) to determine the recommended phase 2 dose (RP2D) for TECVAYLI; Part 2 (dose expansion) to distinguish safety and tolerability of TECVAYLI at the RP2D; Part 3 (the phase 2 component) to evaluate the efficacy of TECVAYLI at the RP2D.^1,2 

MajesTEC-1 Study Protocol - Prohibited Therapies

The following medications were prohibited during the study:

• Any chemotherapy, anticancer immunotherapy (other than TECVAYLI), experimental therapy, 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 the sponsor. For patients where 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 TECVAYLI may be continued.⁴ 
• Plasmapheresis, unless in exceptional circumstances unrelated to disease progression and after consultation with sponsor.⁴
• Corticosteroids in excess of 10 mg daily of prednisone or equivalent is prohibited other than for the management of adverse events where no other treatment options are available and in consultation with the sponsor, or in patients enrolled in the exploratory cohort(s) evaluating low-dose dexamethasone. Dexamethasone should not be administered as pretreatment medication after Cycle 1 Day 1, except for patients who experience Grade ≥2 cytokine release syndrome (CRS) or infusion related reactions (IRRs). Nonsteroidal anti-inflammatory agents should be avoided to minimize the risk of exacerbation of potential sub-clinical myeloma-related kidney disease.²
• Other immunosuppressant agents unless used as protocol-specified pre- or posttreatment medications to treat an adverse event (e.g, CRS).²
• The use of intravenous (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.²
• Routine transfusions should not be given on study drug administration days through Cycle 1. Transfusions should also be avoided on the day of study drug administration during repeat step-up dosing after prolonged treatment interruption.⁴
• The use of transdermal patches at the injection site should be avoided.²
• Cytochrome P450 substrates with a narrow therapeutic index should be used with caution during a CRS event and from the start of step-up doses up to 7 days after the first treatment dose of TECVAYLI is administered.⁴
• For patients receiving warfarin (or other vitamin K antagonists), investigators should consider switching from warfarin (or other vitamin K antagonists) 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.⁴
• Vaccination with live, attenuated vaccine is prohibited within 4 weeks prior to the first dose of TECVAYLI, during treatment, and for 30 days after the last dose of TECVAYLI unless first discussed with the sponsor. Vaccination is allowed per local guidelines (including annual influenza and inactivated severe acute respiratory syndrome coronavirus 2 [SARS CoV-2] vaccines).⁴

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 23 January 2025.