LMY-920 for Treatment of Relapsed or Refractory Myeloma (LMY-920-002)

• ClinicalTrials.gov Identifier: NCT05546723
• Recruitment Status: Not yet recruiting
• First Posted: September 21, 2022
• Last Update Posted: January 13, 2023
• Sponsor: Luminary Therapeutics
• Collaborators: The Cleveland Clinic; Case Western Reserve University
• Information provided by (Responsible Party): Luminary Therapeutics

Study Description

Brief Summary:

Since CAR-T cell treatment of refractory myeloma has shown success, based on preclinical data, we posit that CAR-T cells expressing B-cell activating factor (BAFF) can become another strategy to treat refractory myeloma, even after relapse following BCMA targeting CAR-T cell treatment. This will be phase 1 study of BAFF ligand CAR-T cells in relapsed and refractory myeloma.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma, Refractory; Multiple Myeloma in Relapse	Biological: Autologous CAR-T cell therapy expressing the BAFF-ligand.	Phase 1

Detailed Description:

In this open label, dose escalation study, up to four dose levels of autologous BAFF ligand CAR-T cells (LMY-920) will be evaluated for treatment relapsed and refractory myeloma. BAFF receptor family includes B-cell activating factor receptor (BR3), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design. The primary goal of this study is to determine recommended phase II dose of human LMY-920 in patients with relapsed or refractory myeloma.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: Open label, dose escalation study with up to four dose levels of LMY-920. The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: LUMT1A22, Phase 1 Study of BAFF CAR T Cells (LMY-920) for Treatment of Relapsed or Refractory Myeloma (LMY-920-002)
• Estimated Study Start Date: February 1, 2023
• Estimated Primary Completion Date: October 31, 2024
• Estimated Study Completion Date: December 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: LMY-920 dose escalation; Open label, dose escalation study with up to four dose levels of LMY-920. The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design.	Biological: Autologous CAR-T cell therapy expressing the BAFF-ligand.; LMY-920

Outcome Measures

Primary Outcome Measures :

1. To determine recommended phase II dose of human LMY-920 in patients with relapsed or refractory myeloma. [ Time Frame: 24 months ]
   Maximum tolerated dose

Secondary Outcome Measures :

1. To establish toxicity profile for the infusion of LMY-920. [ Time Frame: 24 months ]
   Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. All adverse events during study will be collected, categorized, and graded. Attribution of relatedness to the investigational agent will be assigned.
2. To determine the objective response rate per International Myeloma Working Group uniform response criteria after treatment with LMY-920 in patients with relapsed or refractory myeloma. [ Time Frame: 24 months ]
   Response rate.
3. To determine the complete response rate per International Myeloma Working Group uniform response criteria after treatment with LMY-920 in patients with relapsed or refractory myeloma. [ Time Frame: 24 months ]
   Response rate.
4. To determine the duration of response. [ Time Frame: 24 months ]
   Duration of response
5. To determine the progression-free survival. [ Time Frame: 24 months ]
   Progression-free survival
6. To determine the overall survival [ Time Frame: 24 months ]
   Overall survival
7. To determine incidence of adverse events [ Time Frame: 24 months ]
   Incidence of adverse events
8. To determine incidence of anti- LMY-920 antibodies [ Time Frame: 24 months ]
   Incidence of anti- LMY-920 antibodies

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects must have histologically confirmed myeloma relapsed or refractory after 3 or more lines of therapy including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. Failing line of therapy is defined accordingly to International Myeloma Workshop Consensus Panel.
2. No evidence of CNS myeloma.
3. Male or female > 18 years of age.
4. ECOG Performance status ≤ 2.

5. Has measurable disease at the time of enrollment as defined by at least one of the following:

   • Serum M-protein greater or equal to 0.5g/dL
   • Urine M-protein greater or equal to 200mg/24hr
   • Serum free light chain (FLC) assay: involved light chain greater or equal to 10mg/dL provided serum FLC ratio is abnormal
   • Bone marrow plasma cells greater than or equal to 30% total bone marrow cells
6. >2 weeks since prior radiation therapy or systemic therapy at the time of leukapheresis.
7. Total bilirubin ≤ 1.5 mg/dL (except in patients with Gilbert's syndrome).
8. AST (SGOT)/ALT ≤ 2.5 X institutional upper limit of normal.
9. Serum creatinine < 2 mg/dL.
10. Cardiac ejection fraction of >45%, and no evidence of pericardial effusion, as determined by an echocardiogram.
11. Adequate pulmonary function as defined as pulse oximetry ≥ 92% on room air.
12. Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document.
13. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 90 days after the BAFF CAR-T cell infusion.
14. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

1. ASCT within 6 weeks of informed consent.
2. History of allogeneic hematopoietic stem cell transplantation.
3. Active graft-versus-host disease.
4. Active central nervous system or meningeal involvement by myeloma. Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced MRI imaging for at least 90 days prior to registration.
5. Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast).
6. Less than 28 days elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection.
7. New York Heart Association class IV congestive heart failure.
8. Cardiovascular disorders including unstable angina pectoris, clinically significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack, or other ischemic event) within 6 months prior to registration.
9. Active infection requiring intravenous systemic treatment.
10. HIV seropositivity.
11. Pregnant or breastfeeding women are excluded from this study because LMY-920 therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with LMY-920, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
12. Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy.
13. Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
14. Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
15. Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
16. Known additional malignancies which require systemic treatment.
17. History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medications (other than low dose steroids) within 6 months.

Contacts and Locations

Contacts

Contact: Leland Metheny, MD; (216) 844-0139; Leland.Metheny@uhhospitals.org

Locations

United States, Ohio

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States, 44106

Contact: Leland Metheny, MD 216-844-0139 Leland.Metheny@uhhospitals.org

Sponsors and Collaborators

Luminary Therapeutics

The Cleveland Clinic

Case Western Reserve University

Investigators

• Principal Investigator: Leland Metheny, MD; University Hospitals Seidman Cancer Center

More Information

• Responsible Party: Luminary Therapeutics
• ClinicalTrials.gov Identifier: NCT05546723
• Other Study ID Numbers: LMY-920-002; LUMT1A22 ( Other Identifier: Cleveland Clinic Taussig Cancer Institute )
• First Posted: September 21, 2022
• Last Update Posted: January 13, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Luminary Therapeutics:

multiple myeloma; CAR-T; BAFF ligand

Additional relevant MeSH terms:

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