Sirolimus Pre-conditioning on T Cell Activity and T-cell Engaging Bispecific Antibody Efficacy in Multiple Myeloma
Impact of Sirolimus Pre-conditioning on T Cell Activity and T-cell Engaging Bispecific Antibody Efficacy in Multiple Myeloma
Christopher Strouse
10 participants
Jun 1, 2026
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria21
- 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.
Exclusion Criteria22
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Participants whose multiple myeloma is progressing at a rapid pace requiring immediate anti-myeloma therapy per assessment by the principal investigator or enrolling investigator are excluded.
- Excluded concomitant medication exposures:
- Exposure to corticosteroids within 1 week of treatment start
- Exposure to calcineurin inhibitor or mTOR inhibitors (tacrolimus, everolimus, temsirolimus, sirolimus)
- Immunomodulatory monoclonal antibodies targeting tumor necrosis factor alpha (e.g. infliximab), interleukin 6 (e.g. siltuximab),
- Janus kinase inhibitors (e.g. ruxolitinib)
- Any other investigational drug within 28 days
- History of allogeneic hematopoietic cell transplantation.
- Excluded concurrent medical conditions:
- Active uncontrolled infection within 7 days prior to treatment start
- Uncontrolled thrombotic event within 3 months of treatment start
- Acute myocardial infarction or acute coronary syndrome within 6 months of start of treatment
- Uncontrolled inflammatory bowel disease
- Active hepatitis B virus, hepatitis C virus, or Human Immunodeficiency Virus infection
- Uncontrolled rheumatologic conditions
- Use of ACE-inhibitor therapy within 1 week of treatment start
- Patients found to be taking ace-inhibitor therapy during screening can be included if the ace-inhibitor is substituted for an angiotensin receptor blocking agent. (https://drug-interactions.medicine.iu.edu/main-table)
- CYP3A4/p-gp inhibitors and inducers for 7 days prior to sirolimus doses and 7 days after sirolimus doses(see appendix A for list)
- Any other current active malignancy or history of metastatic malignancy that has the potential to interfere with the safety or efficacy assessment of the investigational intervention
- Pregnancy or lactation.
- Known allergic reactions to study agent (sirolimus).
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Interventions
Sirolimus is an immunosuppressant drug. Sirolimus binds to FK binding protein 12 and inhibits mTOR. This then suppresses T-cell proliferation and inhibits progression from G1 to S phase of the cell cycle.
Teclistamab is a bispecific antibody that binds the CD3 receptor on T-cells and the B-cell maturation antigen on multiple myeloma cells and healthy B-lineage cells.
Talquetamab is a bispecific antibody that binds the CD3 receptor on T-cells and the GPRC5d receptor on multiple myeloma cells.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07581704