Sirolimus Pre-conditioning on T Cell Activity and T-cell Engaging Bispecific Antibody Efficacy in Multiple Myeloma

NCT07581704 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202601163
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Dose limiting toxicities (DLTs) as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  The incidence of treatment-emergent adverse events will be summarized by system organ class and/or preferred term, type of adverse event, severity (based on NCI CTCAE v5.0) grades), and relation to study treatment. The most severe grade per participant will be reported. Adverse events leading to premature discontinuation from the study intervention and serious treatment-emergent adverse events will be presented in tabular form.

  From treatment initiation through 30 days post last dose of study treatment

• Expansion Cohort: Participants change in the Teffector: Texhausted cell ratio

  Testing the null hypothesis H0: ΔPost-Pre = 0 versus the alternative H1: ΔPost-Pre ≠ 0. Results will be used as preliminary estimates to inform a subsequent larger trial.

  From treatment initiation through 3 months

Secondary Outcomes (4)

• Participant change in the following T-cell subsets: T-regulatory; T-Effector Memory (T-EM); T-Effector Memory expressing RA (T-EMRA)

  From treatment initiation through 3 months

• The proportion of participants with grade 3 or higher CRS

  From treatment initiation through 3 months

• The proportion of participants with grade 3 or highter ICANS

  From treatment initiation through 3 months

• The proportion of participants with a very good partial response (VGPR) or better at 3 months

  Three months after the initiation of treatment

Study Arms (1)

Sirolimus in combination with teclistamab or talquetamab

EXPERIMENTAL

This study is designed to test changes in immune cell populations of patients with multiple myeloma exposed to short pre-conditioning with sirolimus prior to teclistamab or talquetamab. Safety of the combination will also be assessed.

Drug: Sirolimus; Biological: Teclistamab; Biological: Talquetamb

Interventions

Sirolimus DRUG

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.

Also known as: Rapamycin

Sirolimus in combination with teclistamab or talquetamab

Teclistamab BIOLOGICAL

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.

Also known as: Tecvayli

Sirolimus in combination with teclistamab or talquetamab

Talquetamb BIOLOGICAL

Talquetamab is a bispecific antibody that binds the CD3 receptor on T-cells and the GPRC5d receptor on multiple myeloma cells.

Also known as: Talvey

Sirolimus in combination with teclistamab or talquetamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Christopher Strouse: lead

Study Sites (1)

University of Iowa Health Care

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Christopher Strouse, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christopher Strouse, MD

CONTACT

(319) 356-0489; christopher-strouse@uiowa.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: May 5, 2026
• First Posted: May 12, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: June 4, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)