Abstract
TPS8054 Background: DARA, a monoclonal antibody (mAb) against CD38, is approved for RRMM. Combination treatment (Tx) with DARA + DURVA, a mAb against programmed death ligand-1 (PD-L1), may enhance host anti-MM immunity and response. DARA and PD-L1 mAbs have each demonstrated clinical activity in combination with pomalidomide (POM) + low-dose dexamethasone (LoDEX) in MM. Thus, the phase 2 MEDI4736-MM-003 trial is evaluating DURVA + DARA in RRMM, and, in an exploratory analysis, the addition of POM + LoDEX to DARA + DURVA either upon progressive disease (PD) with DARA + DURVA or as up-front Tx will be assessed. Methods: ≈ 144 pts with RRMM are being enrolled. Pts with measurable MM who received ≥ 3 prior anti-MM Txs, including a protease inhibitor and an immunomodulatory agent, or are double-refractory to these 2 agents will be included. Exclusion criteria include allogeneic stem cell transplant (SCT), autologous SCT ≤ 12 weeks, and prior DARA or other CD38 antibody therapies. Primary endpoints are overall response rate (ORR) and safety. Secondary endpoints are time to response, duration of response, progression-free survival, and pharmacokinetics. The study includes a 3 + 3 safety run-in phase to confirm the tolerability of the recommended phase 2 doses (RP2Ds) of DURVA and DARA. Dose-limiting toxicities will be evaluated during the first Tx cycle. Safety and efficacy will be assessed by a Simon 2-stage design (Table). POM + LoDEX may be added to DARA + DURVA in pts who received ≥ 2 cycles of DARA + DURVA and had confirmed PD. Based on preliminary safety and efficacy, the 4-drug regimen may be explored as up-front Tx. Tx with either the 2- or 4-drug regimens will continue until PD or unacceptable toxicity. Pts treated with POM will be followed for second primary malignancies every 6 mos until the end of the trial. To date, 6 pts have enrolled in the run-in phase. Clinical trial information: NCT02807454. [Table: see text]
Published Version
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