Elranatamab in Relapsed/Refractory Multiple Myeloma

Official title

Phase II MRD-Adapted Study of Elranatamab in Relapsed/Refractory

Overview

This study evaluates the efficacy of elranatamab alone in patients with relapsed and/or refractory Multiple myeloma who has previously received 1 to 3 combinations of treatment.

Detailed description

Phase II study of elranatamab in patients with relapsed/refractory multiple myeloma who has received 1 to 3 prior lines of therapy. Patients may enter treatment-free observation period if they have a sustained MRD negative response for greater than 12 months.

Interventions

• Drug Elranatamab
  Subcutaneous injection of elranatamab. If patient achieves MRD negative remission, patient would enter treatment-free observation period with MRD monitoring.

Primary outcome measures

• MRD negativity rate as best response [Time frame: 1 year of starting treatment]

Secondary outcome measures (7)

• Sustained MRD negativity rate at 10^-5 [Time frame: Through study completion, up to 5 years]
• Overall response rate [Time frame: Within 1 year of treatment]
• Complete response rate [Time frame: Within 1 year of treatment]
• Progression free survival [Time frame: Through study completion, up to 5 years]
• Duration of response [Time frame: Through study completion, up to 5 years]
• Safety (cytokine release syndrome, neurotoxicity, treatment-related adverse events) [Time frame: Through study completion, on average 4 weeks (cytokine release syndrome, neurotoxicity); Through study completion, up to 5 years (treatment-related adverse events as assessed by CTCAE v5.0 )]
• Quality of life (questionnaire and by EORTC QLQ-MY20 questionnaire) [Time frame: Through study completion, up to 5 years]

Eligibility criteria

Inclusion criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Prior diagnosis of relapsed/refractory MM and have received 1 to 3 prior lines of therapy as defined by the IMWG criteria (Rajkumar et al., 2014) including anti-CD38 monoclonal antibody, proteosome inhibitor (PI), and immunomodulatory drug (IMiD), and BCMA-directed chimeric antigen receptor T-cell (CAR T-cell) therapy

• Refractory is defined as having disease progression while on therapy or within 60 days of last dose in any line, regardless of response.
• If participant has not received BCMA-directed CAR T-cell therapy, must be ineligible for CAR T-cell therapy or deferred such treatment by participant
• Aged greater or equal to 18 years
• Measurable disease as defined by any of the following:

• Serum M-protein level ≥ 0.5 g/dL by serum protein electrophoresis (SPEP), or
• Urine M-protein ≥ 200mg/24 hours by urine protein electrophoresis (UPEP), or
• Involved serum free light chain ≥ 10 mg/dL (≥100mg/L) AND an abnormal serum free light chain ratio in patients without measurable disease in the serum or urine
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Adequate hematological function defined as

• Absolute neutrophil count (ANC) ≥1,000/mm3 (G-CSF not permitted for at least 1 week prior to the first dose of elranatamab)
• Hemoglobin ≥8.0 g/dL (transfusion support is permitted if completed at least 1 week prior to planned start of dosing)
• Platelet count ≥75,000/mm3 or ≥50,000/mm3 if >50% involvement with plasma cells in the screening bone marrow (transfusion support is permitted if completed at least 1 week prior to planned start of dosing)
• Adequate renal function with estimated creatinine clearance (CrCl) ≥30 mL/min as calculated using Cockcroft-Gault equation.
• Adequate liver function defined as

• Aspartate and alanine aminotransferase (AST and ALT) ≤2.5 x upper limit of normal (ULN); ≤5.0 x ULN if there is liver involvement by the tumor.
• Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN in case of bone metastasis).
• Total bilirubin ≤2.0 mg/dL, except in patients with Gilbert Syndrome who must have a total bilirubin less than 3.0 mg/dL.
• Able to receive outpatient treatment of elranatamab by meeting the following criteria:

• Lives within 30minutes from the site of medication administration
• Reliable caregiver present, who is able to watch participant continuously for at least until 48 hours after administration of first full treatment dose
• No history of grade 3-4 CRS or grade 3-4 ICANS from other immune effector cell or bispecific antibody therapies
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1
• Serum pregnancy test (for females of childbearing potential) negative at screening.

a. Female patients of non-childbearing potential must meet at least 1 of the following criteria: i. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state.

ii. Have undergone a documented hysterectomy and/or bilateral oophorectomy. iii. Have medically confirmed ovarian failure. b. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.

• Agreement to adhere to Lifestyle Considerations (see section 5.3 and Appendix 2) throughout study duration

Exclusion criteria

• Subjects with smoldering multiple myeloma, IgM multiple myeloma, Waldenstrom's macroglobulinemia, amyloidosis, POEMS syndrome, and primary and secondary plasma cell leukemia, defined as circulating plasma cells ≥ 5%
• Extramedullary relapse who does not meet criteria for measurable disease as above
• Active malignancy other than Multiple Myeloma requiring treatment in the past 3 years, with the exception of successfully treated non-metastatic squamous or basal skin carcinoma
• Known CNS involvement by multiple myeloma
• Active, uncontrolled autoimmune disorders
• Active uncontrolled infection. Active infections must be resolved and/or controlled at least 14 days prior to enrollment.
• Radiation therapy within 2 weeks prior to study entry (bone lesions requiring radiation may be treated with limited \[ie, ≤25% of bone marrow in field\] radiation therapy during this period).
• Last systemic treatment within 2 weeks or 5 half lives, whichever is shorter. Subjects can receive a maximum of 160mg of dexamethasone or equivalent during screening, but at least 7 days prior to start of therapy.
• Last radiation treatment to multiple sites within 2 weeks and single site within 1 week
• History of autologous stem cell transplant within 100 days prior to study enrollment.
• History of allogeneic transplant within 1 year prior to study enrollment or active graft versus host disease.
• On immunosuppressive therapy for concurrent comorbid conditions
• Other major uncontrolled medical comorbidities that may put patients at risk of serious adverse event with treatment with study medication.
• Clinically significant, uncontrolled cardiac disease
• Grade ≥2 peripheral sensory or motor neuropathy
• History of Guillan-Barre syndrome
• Other surgical (including major surgery within 14 days prior to enrollment) or psychiatric conditions including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
• Pregnancy or lactation
• Known or suspected hypersensitivity to the study intervention or any of its excipients.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of California San Diego — La Jolla

Identifiers

NCT: NCT06711705 · 810312

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗