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126 Polatuzumab Vedotin Plus Obinutuzumab and Lenalidomide in Patients With Relapsed/Refractory Follicular Lymphoma: Primary Analysis of the Full Efficacy Population in a Phase Ib/II TrialClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Follicular Lymphoma: Biomarkers and Clinical Trials
Hematology Disease Topics & Pathways:
Adult, Biological, Diseases, Therapies, Study Population, Lymphoid Malignancies
Saturday, December 7, 2019: 10:45 AM
Hall E2, Level 2 (Orange County Convention Center)

Catherine Diefenbach, MD1*, Brad S. Kahl, MD2, Lalita Banerjee, FRCPath3*, Andrew K McMillan, FRCP4, Fiona Miall, MD, FRCPath, MRCP, BMBS5*, Javier Briones, MD, PhD6*, Raul Cordoba, MD, PhD7, Jamie Hirata, PharmD8, YiMeng Chang, MSc9*, Lisa Musick, PharmD8* and Pau Abrisqueta, MD, PhD10*

1Perlmutter Cancer Center at NYU Langone Health, New York, NY
2Division of Oncology, Washington University, St Louis, Washington University, St Louis, MO
3Oncology Centre, Maidstone and Tunbridge Wells NHS Trust, Kent, United Kingdom
4Centre for Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
5Department of Haematology, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
6Department of Hematology, Hospital Santa Creu i Sant Pau, Barcelona, Spain
7Fundacion Jimenez Diaz University Hospital, Madrid, Spain
8Genentech, Inc., South San Francisco, CA
9F. Hoffmann-La Roche Ltd, Mississauga, Canada
10Hospital Vall Hebron, Barcelona, Spain

Introduction: Polatuzumab vedotin (Pola) combined with obinutuzumab (G) demonstrated activity and tolerability in a Phase Ib/II trial of patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL; Phillips et al. Blood 2016). In addition, the doublet combination of G plus lenalidomide (Len) showed favorable activity and an acceptable safety profile in a Phase II study of pts with R/R FL (Morschhauser et al. Lancet 2019). We sought to determine whether Pola-G-Len might further enhance anti-tumor response in R/R FL. Here, for the first time, we present the full primary analysis of efficacy and safety data from a Phase Ib/II study (GO29834; NCT02600897) of Pola-G-Len in pts with R/R FL.

Methods: GO29834 is an open-label, multicenter study of pts with R/R FL (excluding grade 3b) who had received ≥1 prior anti-CD20-containing chemo-immunotherapy regimen. An initial 3+3 dose-escalation phase to define the recommended Phase II dose (RP2D) combination for Pola + Len was expanded into Phase II. Pts in the expansion cohort received induction treatment with six 28-day cycles of: G 1000mg IV (Cycle [C]1: Day [D] 1, D8, D15; C2–6: D1); Pola 1.4mg/kg IV (D1), and Len 20mg PO (D1–21). Responders received maintenance treatment for 24 months (G 1000mg on D1 every 2 months and Len 10mg on D1–21 during Months 1–12). The primary endpoint was complete response (CR) at end of induction (EOI), as determined by the Independent Review Committee (IRC) based on positron emission tomography–computed tomography (PET–CT) scans (by modified Lugano 2014 criteria). In addition, progression-free survival (PFS) was determined by the investigator.

Results: At the time of the primary analysis (March 12, 2019), a total of 56 pts from the Phase Ib and Phase II populations were enrolled and had entered induction; the median duration of follow-up was 11.79 months. Baseline characteristics were: median age, 62 years; male, 59%; Ann Arbor Stage III–IV, 88%; Follicular Lymphoma International Prognostic Index high-risk (≥3), 55%; bulky disease (≥7cm), 16%; ≥2 prior lines of therapy, 77%; refractory to last line of prior regimen, 50%; and refractory to last line of anti-CD20 treatment, 45%. All pts had at least one adverse event (AE), 31 (55%) had a serious AE, and 44 (79%) had a grade 3–4 AE. The most common grade 3–4 AEs were neutropenia (28 pts, 50%), thrombocytopenia (13 pts, 23%), infections (9 pts, 16%), and anemia (8 pts, 14%). AEs leading to a dose reduction or interruption of any drug occurred in 19 (34%) and 41 (73%) of pts, respectively; the majority were modifications of Len. In addition, 14 (25%) pts had an AE that led to the discontinuation of any study drug. One grade 5 AE was reported (septic shock); however, it was not considered to be related to study treatment as the pt was receiving a new anti-lymphoma treatment after experiencing disease progression (PD). In the primary efficacy population (n=46), the IRC-assessed modified Lugano objective response rate was 76%, with a CR rate of 65% (Table). A sub-group analysis showed that 71% (15/21) of pts who were refractory to their last treatment achieved a CR. In total, five pts experienced PD, three in C1 or C2 and two at the month 12 response assessment. With a median follow-up duration of 11.27 months, median PFS was not reached.

Conclusions: Our study of the novel triplet combination, Pola-G-Len, demonstrates a safety profile consistent with the known profiles of the individual drugs. This first report of the full efficacy population showed high CR rates at EOI in a heavily pre-treated and refractory population, which compares favorably with currently available R/R FL therapies. These compelling findings support the further investigation of this triplet combination in a larger pt population. To determine the median PFS, a longer period of follow-up, through and beyond maintenance treatment, is ongoing.

Disclosures: Diefenbach: MEI: Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding; Genentech: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding. Kahl: Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; TG Therapeutics: Consultancy; BeiGene: Consultancy. Banerjee: Gilead: Other: Travel; Takeda: Other: Travel; Novartis: Other: Travel. McMillan: Sandoz: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novartis: Honoraria; MSD: Honoraria; Pfizer: Honoraria, Research Funding; BMS: Honoraria; Gilead: Honoraria; Celgene: Honoraria, Speakers Bureau. Miall: F. Hoffmann-La Roche Ltd: Honoraria; Takeda: Honoraria, Other: Conference registration travel expenses. Briones: Roche: Honoraria, Research Funding. Cordoba: Janssen: Consultancy, Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Kyowa-Kirin: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Research Funding, Speakers Bureau; Roche: Honoraria, Speakers Bureau; FUNDACION JIMENEZ DIAZ UNIVERSITY HOSPITAL: Employment; Celgene: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy. Hirata: F. Hoffmann-La Roche Ltd: Equity Ownership; Genentech, Inc.: Employment. Chang: Roche Canada: Employment. Musick: Roche/Genentech: Employment, Equity Ownership. Abrisqueta: Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau.

OffLabel Disclosure: Polatuzumab vedotin (POLIVY, Genentech, Inc.) is a CD79b-directed antibody-drug conjugate. It was approved by the FDA in June 2019 in combination with bendamustine and rituximab for the treatment of adults with relapsed/refractory diffuse large B-cell lymphoma after at least two prior therapies.

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