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THE PI3Kδ INHIBITOR ME‐401 ± RITUXIMAB IN RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL), CHRONIC LYMPHOCYTIC LEUKEMIA (CLL), AND SMALL LYMPHOCYTIC LYMPHOMA (SLL)
Author(s) -
Zelenetz A.D.,
Jagadeesh D.,
Kenkre V.P.,
Reddy N.M.,
Stathis A.,
Salman H.S.,
Asch A.S.,
Soumerai J.,
Jhangiani H.S.,
Iasonos A.,
Patel K.,
Carter J.,
LLorinSangalang J.,
Pagel J.M.
Publication year - 2019
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.133_2629
Subject(s) - medicine , rituximab , follicular lymphoma , chronic lymphocytic leukemia , gastroenterology , refractory (planetary science) , lymphoma , oncology , surgery , leukemia , physics , astrobiology
in R/R FL. We report a pre-planned interim analysis of the safety/efficacy of induction and maintenance with Pola-G-Len in pts with R/R FL in a phase Ib/II study (NCT02600897). Methods: Pts received induction treatment with 6x 28-day (D) cycles (C) of: G 1000mg IV (C1: D1, D8, D15; C2–6: D1); Pola 1.4mg/kg or 1.8mg/kg dose escalation (DE) or recommended phase 2 dose (RP2D; expansion) IV (D1); and Len 10–20mg (DE) or RP2D (expansion) PO (D1–21). Pts with complete response (CR)/partial response (PR)/stable disease (SD) at the end of induction (EOI) received G 1000mg (D1 every 2mo, for 24mo), and Len (10mg, D1–21 monthly, 12mo). Primary endpoints were C1 dose-limiting toxicities (DLTs), safety/tolerability, CR rate at EOI (modified Lugano criteria). Results At the interim data cut-off (6 July 2018), 52 pts were enrolled: 9 discontinued the study (adverse events [AE], n=3; death due to PD, n=4; pt withdrawal, n=1; other, n=1). At baseline, the median pt age was 62 (range 32–87) years; 60% were male; 58% had FLIPI score 3–5; 79% had received ≥2 prior therapy lines; 50% were refractory to their last treatment; 17% had bulky disease (≥7cm). Two DLTs were reported in the cohort receiving Pola 1.8mg/kg + Len 10mg during the DE period (Gr 4 lipase/amylase elevation; asymptomatic, resolved with supportive care; Gr 3 thrombocytopenia leading to a delay in the initiation of cycle 2). Gr ≥3 AEs were experienced by 75% of pts: neutropenia (46%), thrombocytopenia (17%), anemia (12%) and infections (12%) were the most common AEs. Len dose reduction or interruption occurred in 31% and 52% of pts, respectively. One Gr 5 AE was reported (septic shock after PD in pt receiving subsequent therapy). The RP2D was determined as Pola 1.4mg/kg + Len 20mg. Preliminary efficacy data suggest high activity, with an independent review committee-assessed Modified Lugano response rate of 89% and a CR rate of 67% (Table). Median progression-free survival was not reached (median follow-up duration 8.95 mo in the efficacy-evaluable population). Conclusions The safety profile of Pola-G-Len is consistent with known profiles of the individual drugs. Response rates at EOI with Pola-G-Len are promising, with high CR comparedwith available R/R FL treatments. Acknowledgment: Third-party editorial assistance, under the direction of authors was provided by Angela Rogers of Gardiner-Caldwell Communications, and was funded by F Hoffmann-La Roche. © 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.