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