SAFETY OF LISOCABTAGENE MARALEUCEL GIVEN WITH DURVALUMAB IN PATIENTS WITH RELAPSED/REFRACTORY AGGRESSIVE B‐CELL NON HODGKIN LYMPHOMA: FIRST RESULTS FROM THE PLATFORM STUDY

Abstract

Introduction: In the ongoing TRANSCEND NHL 001 study (NCT02631044), lisocabtagene maraleucel (liso-cel; JCAR017), an investigational, anti-CD19 chimeric antigen receptor (CAR) T cell product administered as a defined composition of CD4+/CD8+ CAR T cells, has shown high response rates and a low incidence of severe cytokine release syndrome (CRS) and neurological events (NE) in patients (pts) with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) (Abramson et al, ASCO 2018). Immune system modifiers may further enhance the response and response durability seen with anti-CD19 CAR T cell therapy. The ongoing multiarm, parallel cohort, phase 1/2 PLATFORM study evaluates liso-cel in combination with immune system modifiers in pts with R/R non-Hodgkin lymphoma (NHL). We report preliminary data from the dose escalation part of Arm A, combining liso-cel with the anti-PD-L1 antibody, durvalumab. Methods: Eligible pts had R/R B-cell NHL, ≥2 prior lines of therapy, and ECOG PS ≤1. Pts received lymphodepletion with fludarabine and cyclophosphamide for 3 days before liso-cel was given at 1 of 2 dose levels (DL): DL1 = 50 × 106 or DL2 = 100 × 106 CAR+ T cells. Durvalumab was given as an IV infusion from day 29 at a total dose of 1500 mg/4 weeks for up to 12 months. Efficacy was assessed per the Lugano Classification. Results: At data cutoff, 18 pts were enrolled (DL1 n=9; DL2 n=9). 15 pts (DL1 n=8; DL2 n=7) received liso-cel; 11 pts (DL1 n=8; DL2 n=3) completed at least one durvalumab total dose of 1500 mg/4 weeks (2 pts are awaiting treatment; 1 pt no longer met the eligibility criteria; 1 pt died of sepsis). Among the 11 pts, 7 were male; the age ranged from 53 to 78 years. Ten pts had DLBCL; 1 patient had follicular lymphoma grade 3B. Treatment-emergent adverse events included fever, CRS, and NEs (all grade ≤2), cytopenia, and fatigue related to liso-cel (n=7 pts); and hemolytic anemia, fatigue, and rash related to durvalumab (n=3 pts). Two pts had grade ≥3 related events (neutropenic fever and cytopenia) after durvalumab treatment. No CRS occurred after durvalumab infusion. One pt died of acute respiratory failure after disease progression. No dose-limiting toxicities were observed. The best overall response rate was 91% (10/11); 64% of pts (7/11) achieved a complete response (CR). Among the first 6 pts who received durvalumab, 3 pts showed increased CAR T cells at day 85 compared with pre-durvalumab levels on day 29. One pt maintained CAR T cells near peak expansion levels until day 85 and achieved CR at month 6. Conclusions: Based on preliminary results, the combination of liso-cel with durvalumab has an acceptable safety profile. No CRS was observed after initiation of durvalumab. Preliminary data suggest CAR T cells persist and/or increase with combination treatment, warranting further clinical evaluation. Updated data will be presented. Keywords: CD19; diffuse large B-cell lymphoma (DLBCL); PD-1L. Disclosures: Siddiqi, T: Consultant Advisory Role: AstraZeneca, Juno, Pharmacyclics, BeiGene; Research Funding: Dr. Siddiqi's institution received research funding from Juno, Celgene, Kite, BeiGene, Oncternal Therapeutics, TG therapeutics, Acerta Pharma, Pharmacyclics; Other Remuneration: Speaker for Pharmacyclics, Janssen, Seattle Genetics. Travel, Accommodations, Expenses: Juno. Abramson, J: Consultant Advisory Role: Gilead Sciences, Seattle Genetics, Celgene Novartis, Amgen, Juno Therapeutics, Karyopharm, Verastem, Bayer, Abbvie, Janssen, Merck, Kite Pharma Genentech, EMD Serono; Research Funding: Seattle Genetics, Celgene, Genentech, Juno therapeutics, AI therapeutics. Lee, H: Research Funding: Celgene. Schuster, S: Consultant Advisory Role: Celgene, Novartis, Merck, Genentech, Nordic Nanovector, Gilead; Research Funding: Dr. Schuster's institution received research funding from Novartis, Celgene, Merck, Genentech. Hasskarl, J: Employment Leadership Position: Celgene International; Stock Ownership: Celgene. Montheard, S: Employment Leadership Position: Celgene. Dell Aringa, J: Employment Leadership Position: Celgene. Thompson, E: Employment Leadership Position: Celgene; Stock Ownership: Celgene. Ananthakrishnan, R: Employment Leadership Position: Celgene. Lunning, M: Consultant Advisory Role: AbbVie, Bayer, Celgene, Genentech, Gilead Sciences, Inc, Janssen/Pharmacyclics, Juno Therapeutics, Kite, Novartis, Portola, Sanofi-Genzyme, Seattle Genetics, Spectrum, TG Therapeutics, Verastem; Research Funding: Dr. Lunning's institution received research funding from Celgene, Curis, Janssen Scientific Affairs, LLC, Juno Therapeutics, miRagen, Pharmacyclics, TG Therapeutics.