ELISA in Relapsed/Refractory MM

Официальное название

A Phase 2 Study of Elranatamab in Combination With Isatuximab (ELISA) in Relapsed and Refractory Multiple Myeloma

Обзор

This is an open-label phase 2 study of elranatamab in combination with isatuximab administered subcutaneously in patients with relapsed and refractory multiple myeloma (RRMM) who have received at least two prior lines of therapy and who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). The subcutaneous injection method of isatuximab administration, including the device used to administer isatuximab, is investigational.

Подробное описание

This phase 2, single center, open-label study will enroll 30 patients with relapsed and refractory multiple myeloma (RRMM) who have received at least two prior lines of therapy and who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). Participants with prior therapy with anti-CD38 and anti-B cell maturation antigen (BCMA) target except an anti-BCMA T cell engager (TCE) may be eligible.

This research is being done to see if the study drugs, elranatamab and isatuximab-irfc, reduce the risk of worsening disease and to evaluate the possible risks of the study drugs. Elranatamab is an FDA approved treatment for RRMM. Isatuximab is FDA approved as a treatment option for RRMM when administered intravenously (IV), however isatuximab will be administered as a subcutaneous (SC) infusion (injected under the skin) in this study which is not FDA approved and is investigational. Isatuximab will be administered subcutaneously using an investigational device called the on-body delivery system. The first six patients who complete Cycles 1 and 2 will be assessed for safety and adverse events prior to enrolling all other patients. The research involves screening for eligibility, study treatment and study visits, and follow-up visits. In the beginning (Day 1) of Cycle 1, there may be a 2-8 day inpatient visit so participants can be monitored during their first dose of isatuximab + elranatamab. Participants will receive study treatment until disease progression, unacceptable toxicity, or withdrawal, and will be followed every 3 months for 5 years after their final dose.

Вмешательства

• Препарат elranatamab
  Subcutaneously injected study drug, usually into the abdomen or lower stomach. Each vial of elranatamab contains a sufficient amount of product to ensure an extractable volume of 1.9 mL at a concentration of 40 mg/mL. The dosing is as follows: * Cycle 1 Day 1: 12 mg/0.3 mL * Cycle 1 Day 4: 32 mg/0.8 mL * Cycle 1 Day 8, 15, 22: 76 mg/1.9 mL * Cycles 2-6, Day 1 and 15: 76 mg/1.9 mL * Cycles 7+, Day 1: 76 mg/1.9 mL
• Препарат Isatuximab SC
  Isatuximab (SAR650984) is an IgG1 derived monoclonal antibody binding selectively the human CD38 membrane protein. Subcutaneously (SC) injected study drug with each vial containing 140 mg/mL (1400 mg/10mL) isatuximab. Isatuximab SC will be injected using the investigational OBDS and in the following doses: * Cycles 2-6, Day 1 and 15: 1400 mg/10 mL * Cycles 7+ Day 1: 1400 mg/10 mL
• Устройство Isatuximab SC-OBDS
  The On Body Delivery System (OBDS) also called Isatuximab SC Wearable Injection System, is a sterile, single-use, disposable, elastomeric, user-filled investigational medical device. The OBDD has a reservoir for the drug product (isatuximab). A self-contained, integrated needle (with manual insertion and automatic retraction mechanism) is provided within the OBDS. The OBDS will be used to inject isatuximab each time the participant receives isatuximab in this study. Study drug administration wil

Первичные конечные точки

• Objective response rate (ORR) [Срок оценки: Day 1 to 2 years post-treatment.]

Вторичные конечные точки (5)

• Incidence of Drug Related Toxicities [Срок оценки: Day 1 to 30 days post-treatment (30 days post last dose). Participants can receive treatment until disease progression, unacceptable toxicity, or withdrawal.]
• Median Progression Free Survival (PFS) [Срок оценки: Day 1 through end of follow-up, up to 5 years.]
• Median Overall Survival (OS) [Срок оценки: Day 1 through end of follow-up, up to 5 years.]
• Rate of Minimal Residual Disease (MRD) status in participants who have achieved very good partial response (VGPR) or complete response (CR) [Срок оценки: Screening through 24 months on treatment.]
• Sustained minimal residual disease (MRD) negative status [Срок оценки: Day 1 through 24 months on treatment.]

Критерии участия

Критерии включения

• 1\. This study will enroll patients with relapsed and refractory multiple myeloma who have had at least 2 prior lines of therapy including patients who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). Prior therapy with anti-CD38 and anti-B cell maturation antigen (BCMA) target will be permitted except an anti-BCMA T cell engager. Patients cannot be refractory to an anti-CD38 antibody.
• 2\. Measurable disease of multiple myeloma as defined by at least one of the following:

• a. Serum monoclonal protein ≥ 0.5 g/dL. Patients with IgD disease and lower amounts of monoclonal protein may be permitted to enroll with PI approval
• b. ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
• c. Serum free light chain ≥ 100 mg/L (10 mg/dL) and abnormal serum free kappa to serum free lambda light chain (FLC) ratio (<0.26 or >1.65)
• 3\. Age ≥18 years.

--a. The effects of elranatamab and isatuximab on the developing human fetus are unknown. For this reason and because anti-BCMA bispecific antibodies are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after the last dose of elranatamab and 5 months after the last dose of isatuximab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

• 4\. ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• 5\. Participants must have adequate organ and marrow function as defined below:

• a. ANC ≥ 1000/μL. G-CSF is not permitted within 7 days of screening.
• b. Platelet count ≥ 50,000/µL. Platelet transfusion is not permitted within 7 days of screening.
• c. Hemoglobin ≥ 8 g/dL. Red blood cell transfusions are permitted to meet eligibility criteria.
• d. Calculated creatinine clearance of ≥ 30 mL/min by Cockcroft-Gault equation.
• e. Patient has adequate hepatic function, as evidenced by each of the following:

• Serum bilirubin values < 2 mg/dL; and
• Serum aspartate transaminase (ALT) and/or aspartate transaminase (AST) values< 2.5 × the upper limit of normal (ULN) of the institutional laboratory reference range. Patients with elevated bilirubin due to Gilbert's syndrome may be permitted with PI approval (i.e., total bilirubin <3 mg/dL and normal direct bilirubin).
• 6\. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• 7\. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
• 8\. Ability to understand and the willingness to sign a written informed consent document.

Критерии исключения

• 1\. Patients with active plasma cell leukemia, POEMS syndrome, or amyloidosis are excluded from this trial.
• 2\. Stem cell transplant within 12 weeks prior to enrollment, or active GVHD.
• 3\. Ongoing Grade ≥2 peripheral sensory or motor neuropathy.
• 4\. History of any grade peripheral sensory or motor neuropathy with prior BCMA directed therapy. History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
• 5\. Previous treatment with an anti-BCMA bispecific T cell engager.

--a. Prior treatment with anti-BCMA CAR-T and/or ADC therapy is permitted; however, the participant cannot be refractory to this therapy if it was administered as the last line prior to study enrollment.

• 6\. Participants who are receiving any investigational agents currently.
• 7\. Participants who have had myeloma therapy or investigational drug within 2 weeks prior to start of treatment or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
• 8\. Known or suspected hypersensitivity to the study drug or any components of the device (e.g. adhesive which contains acrylic).
• 9\. Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrollment:

• a. Acute myocardial infarction, acute coronary syndromes (e.g., unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, pericardial effusion);
• b. Clinically significant cardiac arrhythmias (e.g., uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
• c. Thromboembolic or cerebrovascular events (e.g., transient ischemic attack, cerebrovascular accident, deep vein thrombosis \[unless associated with a central venous access complication\] or pulmonary embolism);
• 10\. Participants with known active HBV, HCV, HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 14 days prior to enrollment. Per institutional protocol, HBV DNA testing by PCR is mandatory for subjects at risk for HBV reactivation.
• 11\. Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ and or other cancers treated with curative intent.
• 12\. Other surgical (including major surgery within past 14 days prior to enrollment) medical or psychiatric condition 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.
• 13\. Live attenuated vaccine within 30 days of the first dose of study intervention.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Massachusetts General Hospital — Boston
• Beth Israel Deaconess Medical Center — Boston
• Dana Farber Cancer Institute — Boston

Идентификаторы

NCT: NCT06832865 · 24-727

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗