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988 Glofitamab in Combination with Polatuzumab Vedotin Maintains Durable Responses and a Manageable Safety Profile in Patients with Heavily Pre-Treated Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) Including High-Grade B-Cell Lymphoma (HGBCL): Extended Follow-up of a Phase Ib/II Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Chemotherapy-free Combinations for Relapsed Aggressive Lymphomas
Hematology Disease Topics & Pathways:
Research, Clinical trials, Combination therapy, Lymphomas, Bispecific Antibody Therapy, Clinical Research, Diseases, Aggressive lymphoma, Treatment Considerations, Biological therapies, Immunotherapy, Lymphoid Malignancies
Monday, December 9, 2024: 5:15 PM

Martin Hutchings1*, Anna Sureda Balari, MD, PhD2, Francesc Bosch3*, Thomas Stauffer Larsen, MD, PhD4*, Paolo Corradini, MD5, Abraham Avigdor, MD6, María José Terol7*, Antonio Rueda Dominguez8*, Antonio Pinto9*, Alan P Skarbnik, MD10, Raul Cordoba, MD, PhD11, Judit Mészáros Joergensen, MD, PhD12*, Pier Luigi Zinzani, MD, PhD13, Ronit Gurion14*, Neta Goldschmidt15*, Wilfred Leung16*, Donghang Li17*, James Relf18*, Maneesh Tandon18*, Gila Sellam19* and Giuseppe Gritti, MD, PhD20*

1Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
2Clinical Hematology Department, Institut Català d’Oncologia – L’Hospitalet, IDIBELL, Universitat de Barcelona, Barcelona, Spain
3University Hospital Vall d'Hebron, Barcelona, Spain
4Odense University Hospital, Odense, Denmark
5University of Milan and Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
6Sheba Medical Center, Ramat Gan and Tel Aviv University, Tel Aviv, Israel
7Hospital Clínico Universitario INCLIVA, University of Valencia, Valencia, Spain
8Virgen de la Victoria University Hospital, Málaga, Spain
9National Cancer Institute Fondazione G. Pascale IRCCS, Naples, Italy
10Novant Health Cancer Institute, Charlotte, NC
11Fundación Jiménez Díaz University Hospital, Madrid, Spain
12Aarhus University Hospital, Aarhus, Denmark
13University of Bologna, Bologna, Italy
14Institute of Hematology, Davidoff Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
15Department of Hematology, Hadassah Medical Center, Jerusalem, Israel
16Genentech, Inc., South San Francisco, CA
17Roche (China) Holding Ltd, Shanghai, China
18Roche Products Ltd, Welwyn Garden City, United Kingdom
19F. Hoffmann-La Roche Ltd, Basel, Switzerland
20ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy

Background: The CD20xCD3 bispecific antibody glofitamab (Glofit) engages and redirects T cells to eliminate B cells. Polatuzumab vedotin (Pola), an antibody-drug conjugate targeting CD79b, has a complementary mechanism of action to Glofit. In this open-label, multicenter, Phase Ib/II study (NCT03533283), Glofit+Pola demonstrated durable responses and manageable safety in patients (pts) with R/R LBCL (Hutchings, et al. ASH 2023). We present updated results with longer follow-up in a greater number of pts with R/R LBCL, including pts with HGBCL and prior chimeric antigen receptor (CAR) T-cell therapy, at the previously confirmed recommended Phase II dose of Glofit (30mg, from Part I of the study) when combined with Pola.

Methods: Pts received 1000mg obinutuzumab pre-treatment (Gpt) on Cycle (C)1 Day (D)1, 7 days prior to the first Glofit dose to mitigate risk of cytokine release syndrome (CRS). Pola 1.8mg/kg was given on C1D2 and D1 of C2–6 (21-day cycles), and Glofit as step-up dosing in C1 (D8, 2.5mg; D15, 10mg) followed by the target dose (30mg) on D1 of C2–12 (21-day cycles). Fixed treatment of 6 cycles of Pola and 12 cycles of Glofit were administered, unless pts discontinued treatment due to disease progression, unacceptable toxicities, or withdrawal of consent.

Results: At the clinical cutoff date (CCOD; Feb 16, 2024), 129 pts had received ≥1 dose of study treatment (DLBCL, n=57; HGBCL, n=44; transformed follicular lymphoma [trFL], n=26; primary mediastinal LBCL [PMBCL], n=2). Median age was 67 years (range: 23–84), 64% were male (n=82), median prior lines of therapy was 2 (range: 1–7), 71% were refractory to the last line of prior therapy (n=92), and 22% received prior CAR T-cell therapy (n=28; 17% were refractory [n=22]); 43% of pts completed treatment (n=56), 7% had treatment ongoing, and 50% discontinued treatment (n=64; primarily due to progressive disease [33%; n=42/129]). Of 128 efficacy-evaluable pts, best overall response rate (ORR; per Lugano 2014) was 80%, with a complete response (CR) rate of 62%. By histology, best ORR and CR rate, respectively, were: DLBCL 84% (48/57) and 61% (35/57); HGBCL 79% (34/43) and 65% (28/43); trFL 73% (19/26) and 54% (14/26); PMBCL 100% for ORR and CR (2/2). In pts who had prior CAR T-cell therapy (n=28), ORR was 75% and CR rate was 50%. With a median follow-up of 23.5 months (range: 0–46), median progression-free survival (PFS) was 12.3 months (95% confidence interval [CI]: 8.8–23.5). Median PFS by histology was 10.4 months (95% CI: 7.0–22.8) for DLBCL, 9.6 months (95% CI: 5.1–33.0) for trFL, and 15.5 months (95% CI: 9.3–not reached [NR]) for HGBCL. Median PFS follow-up was 26.3, 30.3, and 9.3 months for DLBCL, trFL, and HGBCL, respectively. Median duration of response was 21.9 months (95% CI: 14.3–37.8). Median duration of complete response was 31.8 months (95% CI: 21.1–NR); 64.6% of complete responders were in remission at CCOD. Median overall survival (OS) was 39.2 months (95% CI: 20.6–NR), with a 24-month OS event free rate of 54%. The most common adverse event (AE) was CRS (43%), which was mostly Grade (Gr) 1–2 (Gr 1 27%, Gr 2 15% per ASTCT criteria); one pt had Gr 3 CRS and one had fatal Gr 5 CRS (occurred in the context of unresolved infection; pt declined further CRS management at Gr 3). CRS events were managed with tocilizumab (34%), fluids (23%), low flow oxygen (20%), or corticosteroids (14%) and 3 pts (5.4%) were admitted to intensive care. Neurologic AEs potentially consistent with immune effector cell-associated neurotoxicity syndrome occurred in 4 pts (Gr 1, n=2; Gr 2, n=1; Gr 3, n=1 [syncope]), all in the context of CRS. Gr 3–4 AEs occurred in 59% of pts, mostly neutropenia (32%); febrile neutropenia was reported in 2 pts (1.6%). Serious AEs occurred in 60% of pts and 8% of pts had Gr 5 AEs (5/10 due to COVID-19). In total, 11% of pts discontinued Glofit due to AEs (3/14 due to COVID-19; 1 pt due to COVID-19 pneumonia); 5% of pts withdrew from Glofit treatment due to Glofit-related AEs and 5% withdrew due to Pola-related AEs. Exploratory biomarker analyses including response in molecular subgroups and circulating tumor DNA kinetics will be presented.

Conclusions: Heavily pretreated pts with R/R LBCL treated with Glofit+Pola continued to demonstrate high and durable response rates across all histologies, including pts with HGBCL and those who had received prior CAR T-cell therapy. The safety profile was manageable and consistent with the known profiles of the individual drugs.

Disclosures: Hutchings: AbbVie, AstraZeneca, Genmab, Johnson & Johnson, Merck, F. Hoffmann-La Roche Ltd, Takeda: Consultancy; AbbVie, AstraZeneca, Bristol Myers-Squibb, Celgene, Genentech, Inc., Genmab, Incyte, Johnson & Johnson, Merck, Novartis, F. Hoffmann-La Roche Ltd, Takeda: Research Funding; AbbVie, AstraZeneca, Genmab, Johnson & Johnson, Merck, F. Hoffmann-La Roche Ltd, Takeda: Honoraria. Sureda Balari: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; Takeda Pharmaceutical: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Other: Travel Expenses; Alexion: Honoraria; GETH-TC: Other: President; EBMT: Other: President; GSK: Consultancy, Honoraria, Speakers Bureau; Mundipharma: Consultancy; Bluebird: Membership on an entity's Board of Directors or advisory committees. Bosch: F. Hoffmann-La Roche Ltd, Janssen, AbbVie, Novartis, Celgene, Gilead, Takeda, AstraZeneca, BeiGene, Lilly: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd, Novartis, Janssen, AbbVie, Gilead, Mundipharma, Celgene, Takeda, AstraZeneca, Celgene/BMS, BeiGene, Lilly: Other; F. Hoffmann-La Roche Ltd, Novartis, Janssen, AbbVie, Gilead, Mundipharma, AstraZeneca, Celgene/BMS, Takeda, Ascentage, Lilly, BeiGene: Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd, Celgene/BMS, Karyopharm, Takeda, AstraZeneca, Novartis, AbbVie, Janssen: Research Funding; Vall d’Hebron University Hospital (Barcelona, Spain): Current Employment; F. Hoffmann-La Roche Ltd, Novartis, Janssen, AbbVie, Gilead, Mundipharma, Takeda, Celgene/BMS, AstraZeneca, Lilly, BeiGene, TG Therapeutics, Ascentage: Consultancy. Larsen: Roche: Consultancy; Kite/Gilead: Consultancy; Genentech: Research Funding. Corradini: Sanofi: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); SOBI: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Takeda: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Novartis: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Pfizer: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Roche: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Kyowa Kirin: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Janssen: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Daiichi Sankyo: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Gilead/Kite: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; GlaxoSmithKline: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Incyte: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Celgene: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Amgen: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; AbbVie: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Bristol Myers Squibb: Other: Support for travel and accommodations. Avigdor: Eli Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding, Speakers Bureau; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Karyospharm: Research Funding; TG Therapeutics: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Ascentage: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau. Terol: AWAITING DOI: Current Employment. Rueda Dominguez: BMS/Celgene: Research Funding; Roche, Takeda, BMS, Gilead, MSD, Incyte, Merck C.O.: Speakers Bureau; Roche and MSD: Other: Travel expenses. Pinto: Merck Sharp and Dohme: Honoraria; Incyte: Honoraria; IGM Biosciences: Current holder of stock options in a privately-held company; Autolus Therapeutics: Current holder of stock options in a privately-held company; Hoffmann-La Roche AG: Consultancy, Honoraria; Kite-Gilead: Honoraria; Bristol Myers Squibb: Honoraria; BeiGene: Honoraria; Eli Lilly: Honoraria. Skarbnik: Kite: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Genentech: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Alexion: Consultancy, Honoraria, Speakers Bureau; Beigene: Honoraria, Speakers Bureau; Acerta Pharma: Research Funding; Gilead Sciences: Honoraria; Novartis: Honoraria; Epizyme: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Honoraria, Speakers Bureau; Lilly: Consultancy, Honoraria, Speakers Bureau; Genmab: Consultancy, Honoraria, Speakers Bureau; SeaGen: Consultancy, Honoraria, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Research Funding; Verastem: Honoraria, Research Funding. Cordoba: Genmab: Consultancy; BMS: Consultancy, Speakers Bureau; Kite: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Johnson & Johnson: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Kyowa Kirin: Consultancy; Pfizer: Research Funding. Joergensen: Kite/Gilead: Consultancy; Novo Nordisk: Current holder of stock options in a privately-held company; Sobi: Consultancy; Caribou: Consultancy; Incyte: Consultancy; Abbvie: Consultancy; Roche: Consultancy. Zinzani: SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ASTRAZENECA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TAKEDA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC THERAPEUTICS: Membership on an entity's Board of Directors or advisory committees; INCYTE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BEIGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SECURA BIO: Membership on an entity's Board of Directors or advisory committees. Gurion: F. Hoffmann-La Roche Ltd, Medison, AbbVie, Takeda, Eli Lilly, Novartis: Consultancy; F. Hoffmann-La Roche Ltd, Medison, AbbVie, Takeda, Eli Lilly, Novartis: Honoraria. Goldschmidt: Abbvie, Janssen, AstraZeneca: Consultancy. Leung: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Li: Roche (China) Holding Ltd: Current Employment. Relf: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months; Roche Products Ltd: Current Employment; F-star Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months. Tandon: Roche Products Ltd: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Sellam: F. Hoffmann-La Roche Ltd: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Gritti: Janssen, Beigene, Kite-Gilead, Roche, Sandoz: Other: Support for attending meetings; Ideogen, Takeda: Speakers Bureau; Takeda, Abbvie, Roche, Kite-Gilead, Ideogen, Genmab: Membership on an entity's Board of Directors or advisory committees.

OffLabel Disclosure: All study therapy constituted investigational or off-label use. Glofitamab (Columvi) is a bispecific CD20-directed CD3 T-cell engager approved for treating adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), or large B-cell lymphoma from follicular lymphoma (FL), after two or more lines of systemic therapy. Polatuzumab vedotin (Polivy) is a CD79b-directed antibody-drug conjugate indicated for use in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of adult patients with previously untreated DLBCL, NOS, or high-grade B-cell lymphoma (HGBL) with an International Prognostic Index (IPI) score of 2 or higher. It is also indicated for use with bendamustine and a rituximab product in adult patients with relapsed or refractory DLBCL, NOS, after at least two prior therapies.

*signifies non-member of ASH