P-206: SELECT Trial in Progress: an open-label, phase 2 study of Carfilzomib, Pomalidomide, and Dexamethasone in patients with first or second relapse of Multiple Myeloma

Background Combination therapies comprised of proteasome inhibitors (PI), immunomodulatory drugs (IMiD), and monoclonal antibodies +/- autologous stem cell transplant have significantly improved outcomes for patients (pts) with multiple myeloma (MM). However, many pts relapse despite achieving complete response (CR). Lenalidomide (R) is part of standard of care in newly diagnosed MM, resulting in many pts being refractory at first relapse. There is an emerging unmet need for effective regimens that induce deep responses in the early (first or second) relapsed setting. Minimal residual disease (MRD) is a sensitive measure with deep prognostic value for clinical outcomes, with results influencing subsequent treatment decisions. The IMiD pomalidomide (P) has synergistic activity when combined with a PI plus dexamethasone (d) in pts with relapsed MM refractory to R (Richardson 2019). Carfilzomib (K), a second-generation PI, is approved in combination with d, and as a triplet with daratumumab (KdD) or R (KRd) for pts with MM and 1–3 prior therapies. Phase 1/2 studies have shown that adding K to Pd is well tolerated and effective in heavily pre-treated pts, including those refractory to R (Bringhen 2018). The SELECT trial will evaluate the novel primary endpoint of MRD-negative CR to assess efficacy of KPd in pts with 1 or 2 relapses of MM. Methods This ongoing, open-label phase 2 study (NCT04191616) will enroll ~85 adult pts with MM who have received 1 or 2 prior lines of therapy and are refractory to R. Pts will be treated until disease progression. Prior exposure to PI or anti-CD38 antibody is allowed. Pts previously exposed to K must have responded with at least partial response, must not have discontinued due to toxicity, may not have relapsed while receiving or within 60 days of the last dose of K, and not had K in the last 6 months. Patients with prior P exposure are excluded. K will be given intravenously (IV) (20 mg/m2 on Cycle 1, Day 1; 56 mg/m2 thereafter) on Days 1, 8, and 15 of each 28-day cycle for Cycles 1–12 and on Days 1 and 15 from Cycle 13 until progression or end of study. P (4 mg) will be given orally on Days 1–21 of all cycles. Oral or IV d will be given prior to K at a dose of 40 mg (20 mg for pts ≥75 years of age) on Days 1, 8, 15, and 22 of Cycles 1–12, and at 20 mg (10 mg for pts ≥75 years of age) on Days 1 and 15 of Cycles 13 onwards. The primary endpoint is MRD–negative CR in bone marrow at 12 months by next generation sequencing (sensitivity of 10-5). Secondary endpoints include overall response rate, best MRD-negative response at any time, sustained MRD-negative CR, duration of response, time to response, progression-free survival, overall survival, and safety. SELECT is actively enrolling at ~40 sites in Denmark, France, Germany, Greece, Italy, Spain, and the United States, with expansion to more countries planned. 26 pts are currently enrolled; the target for enrollment completion is January 2022.