Ixazomib-pomalidomide-dexamethasone as Second or Third-line Combination Treatment for Patients With Relapsed and Refractory Multiple Myeloma Previously Treated With Daratumumab, Lenalidomide and Bortezomib

Multiple Myeloma in Relapse, Refractory Multiple Myeloma

Adult patients with a confirmed diagnosis of symptomatic and relapsed and/or refractory MM, after receiving bortezomib, lenalidomide and daratumumab during first and second lines, will be eligible to be enrolled in this study. During the first three treatment cycles, patients will be seen twice (Days 1 and 15 of the cycle). Starting from cycle 4 and on, patients will be assessed once per cycle (Day 1), until disease progression, for disease response and progression according to the International Myeloma Working Group (IMWG) criteria. After progression, all patients will be followed for survival; for this purpose, patients will be contacted every 12 weeks until death or termination of the study by the Sponsor. Patients may continue to receive treatment for 24 months or until disease progression (PD) or unacceptable toxicity, the earlier of the three. Dose modifications may be made based on toxicities. Patients who complete study therapy will continue to receive treatment per standard of care.

This phase 2, open-label, single-arm, prospective, multicenter study will evaluate the safety, tolerability and efficacy of ixazomib-pomalidomide-dexamethasone (IPD) as a second or third-line combination treatment for patients with relapsed and/or refractory multiple myeloma (RRMM) who progressed after receiving bortezomib, lenalidomide and daratumumab during first and second lines. The patient population will consist of adult men and women who have a confirmed diagnosis of MM, who have received two prior lines of therapy, and who meet other outlined eligibility criteria. Following confirmation of eligibility, enrolled patients will be treated with pomalidomide plus dexamethasone as standard of care and will also receive ixazomib as a study drug. The treatment regimen will involve administration of the following drugs: Cycles 1-3: during each 21-day cycle: * ixazomib 3 mg on Days 1, 4, 8 and 11 * pomalidomide 4 mg on Days 1 through 14 * dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16 Cycle 4 and consequently: during each 28-day cycle: * ixazomib 4 mg on Days 1, 8 and 15 * pomalidomide 4 mg on Days 1 through 21 * dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22 and 23 Patients may continue to receive treatment for 24 months or until disease progression (PD) or unacceptable toxicity, the earlier of the three. Dose modifications may be made based on toxicities. Patients who complete study therapy will continue to receive treatment per standard of care. The main efficacy outcome- Progression Free Survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause. PFS will be determined by an investigator, based upon laboratory data, as defined by the IMWG criteria. Secondary Endpoints:Objective response rate (ORR)is defined as the proportion of patients who achieve a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), as defined using the IMWG criteria. Overall Survival (OS) OS is defined as the time between the date of first dose and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive. Time to Response (TTR) Time to Response is defined as the time from the first dose to the date of the first sCR, CR, VGPR, or PR. TTR will be evaluated for responders Duration of Response (DOR) Duration of Response is defined as the time between the date of first response to the date of the first objectively documented tumor progression as assessed by study steering committee according to modified IMWG criteria or death due to any cause prior to subsequent anti-cancer therapy. Optional Exploratory Analysis RNA sequencing (by Massive Parallel (MARS)-seq method) of fresh or frozen cluster of differentiation 38+ (CD38+)/CD138+ plasma cells (normal and malignant) in the bone marrow of patients

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