Cevostamab Following CAR T Cell Therapy for RRMM

NCT05801939 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 853124, UPCC 02423
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2, open-label, single-arm, single stage, single-institution study, with an initial safety run-in period. Potential participants with relapsed/refractory myeloma who are undergoing standard of care, commercially-available BCMA-directed CAR T cell therapy may be identified pre-CAR T cell infusion but are not consented and enrolled until at least 4-6 weeks after CAR T cell infusion, once recovered from acute toxicities. Note: the lymphodepleting chemotherapy and CAR T cell therapy is being administered as part of standard clinical practice and is not considered part of this protocol. Alternative lymphodepleting regimens other than fludarabine and cyclophosphamide (eg in the setting of fludarabine shortages) are acceptable. Cevostamab will be given as an IV infusion once every 3 weeks, starting roughly 10 weeks (day 70 +/- 4 days) post-CAR T cell infusion, with subjects planned to receive 8 cycles initially. Aiming to assess the impact of cevostamab consolidation post-BCMA CAR T cell therapy on rate of MRD-negative complete remission (CR) at 12 months.

Conditions

Relapsed/Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• MRD-negative complete remission (CR)

  The proportion of participants who achieve CR as well as MRD-negativity at 12 months post-CAR T cell therapy.

  12 months

Secondary Outcomes (3)

• Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) of cevostamab administration post-BCMA CAR T cell therapy

  infusion start Day 56 through 30 days post final infusion

• Feasibility of cevostamab administration post-BCMA CAR T cell therapy

  Day 56 and completion through day 203

• Impact of cevostamab consolidation post-BCMA CAR T cell therapy on other clinical outcomes

  6 and 12 months post-CAR T cell therapy

Study Arms (1)

Cevostamab

EXPERIMENTAL

Drug: Cevostamab

Interventions

Cevostamab DRUG

Cevostamab will be given as an IV infusion once every 3 weeks, starting roughly 10 weeks (day 70 +/- 4 days) post-CAR T cell infusion, with subjects planned to receive 8 cycles initially. Subjects receive a single step-up dose of 3.6 mg of cevostamab on cycle 1, day 1 (C1D1), followed by the recommended target dose (160 mg, 132mg, or 90 mg based on results of safety run-in data and safety review) on C1D8. Myeloma responses are assessed every cycle, and a repeat bone marrow aspirate and biopsy (BMbx) is performed at the start of cycle 8. If participants are not in an MRD-negative CR at this timepoint (or if the BM bx is inevaluable/indeterminate for CR or MRD testing), they continue with another 8 cycles (C9-16) of cevostamab. If they are in MRD-negative CR at start of C8, they stop therapy after receiving this cycle and are observed.

Cevostamab

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form(s)
• Age ≥18 years at time of signing Informed Consent Form
• Ability to comply with the study protocol
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• Participants must have relapsed and/or refractory multiple myeloma with therapy that must include a proteasome inhibitor, immunomodulatory drug (IMiD), and anti-CD38 antibody, and have received a BCMA-directed CAR T cell product as standard of care (i.e. not on a clinical trial) as per the current FDA label, between 6 and 10 weeks prior to enrollment, and have not had progressive disease by IMWG criteria since CAR T cell infusion. Patients who have received out-of-specification CAR T cell products are not eligible.
• For patients who received ide-cel, they must have had at least 2 prior lines of therapy prior to ide-cel
• For patients who received cilta-cel, they must have had at least 2 prior lines prior to cilta-cel, or 1 prior line and be refractory or intolerant to lenalidomide.
• Agreement to provide bone marrow biopsy and aspirate samples
• Non-hematologic adverse events from prior anti-cancer therapy resolved to Grade ≤ 1, with the certain exceptions.
• Measurable disease is not required for study entry
• Laboratory values as specified in the protocol.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, as defined in the protocol.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined in the protocol.

You may not qualify if:

• Inability to comply with protocol-mandated hospitalization and activities restrictions
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the last dose of study drug
• a. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
• Participants who had ≥ Grade 3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) by ASTCT criteria, or any grade macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH)after CAR-T therapy are excluded
• Participants who had any grade movement and/or neurocognitive disorder attributed to CAR T cells are excluded.
• Prior treatment with systemic immunotherapeutic agents, including, but not limited to, cytokine therapy and anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first cevostamab infusion
• Known treatment-related, immune-mediated adverse events associated with prior immunotherapeutic agents as specified in the protocol.
• Treatment with any chemotherapeutic agent, or any other anti-cancer agent (investigational or otherwise) during the time period between CAR T cell infusion and first cevostamab infusion, with certain exceptions.
• Received systemic immunosuppressive medications (including, but not limited to, steroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, tocilizumab, siltuximab, anakinra, ruxolitinib, and anti-tumor necrosis factor agents), with the exception of corticosteroid treatment ≤ 10 mg/day prednisone or equivalent, within 2 weeks prior to first dose of cevostamab
• a. Participants who received acute, low-dose, systemic immunosuppressant medications (e.g., single dose of dexamethasone for nausea) may be enrolled in the study.
• i. The use of inhaled corticosteroids is permitted. ii. The use of mineralocorticoids for management of orthostatic hypotension is permitted.
• iii. The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted.
• Autologous stem cell transplantation (SCT) within 100 days prior to first cevostamab infusion
• Prior allogeneic SCT within 12 months prior to first cevostamab infusion. Participants with prior allogeneic SCT must have no evidence for active graft-versus-host-disease (GVHD) and be off all therapy for GVHD for at least 3 months prior to first cevostamab infusion.
• Prior solid organ transplantation

Sponsors & Collaborators

• University of Pennsylvania: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

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

Study Officials

• Adam D Cohen, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 6, 2023
• Study Start: July 11, 2023
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)