Impact of Sirolimus Pre-conditioning on T Cell Activity and T-cell Engaging Bispecific Antibody Efficacy in Multiple Myeloma
This is a single center, single arm Phase Ib study with expansion cohort designed to establish the safety and physiologic effects of sirolimus pre-conditioning followed by T-cell engaging bispecific antibody therapy.
∙ To be eligible to participate in this study, an individual must meet all of the following criteria:
• Willingness and ability to provide signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Aged 18 years of older.
• Diagnosis with multiple myeloma, per IMWG Consensus Criteria.20
• Planned for treatment with teclistamab, or talquetamab per standard of care, label indications.15
• Prior exposure to any of the following types of T-cell engaging therapies.
‣ Anti-BCMA x CD3 bispecific antibody (for example: teclistamab, elranatamab)
⁃ Anti-GPRC5d x CD3 bispecific antibody (for example: talquetamab)
⁃ Anti-GPRC5d x CD3 x CD38 trispecific antibody
⁃ Anti-BCMA x CD3 x CD38 trispecific antibody
⁃ Anti-BCMA x CD3 x GPRC5d trispecific antibody
⁃ Anti-BCMA chimeric antigen T-cell (for example: idecabtagene vicleucel, ciltacabtagene autoleucel)
⁃ Anti-FcRL5 x CD3 bispecific antibody
• Required clinical laboratory values during screening phase
∙ Hematologic Parameters Hemoglobin ≥7.0 g/dL; Platelets ≥25 x 109/L; Absolute Lymphocyte Count ≥0.2 x 109/L
∙ Chemistries AST/ALT \< 5 x the ULN; Total Bilirubin \< 3 x the ULN
• Ability to take oral medication and be willing to adhere to the sirolimus pre-conditioning regimen.
• ECOG performance status of 0, 1, or 2 (KPS of \>50).
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner per section5.3.
• Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration.