-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

533 Mosunetuzumab Plus Polatuzumab Vedotin Has Promising Efficacy and a Favorable Safety Profile in Patients with Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma: Updated Results from a Phase Ib/II Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Real World evidence for CAR-T Management I
Hematology Disease Topics & Pathways:
Biological, Lymphomas, Non-Hodgkin Lymphoma, Bispecific Antibody Therapy, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies
Sunday, December 12, 2021: 5:30 PM

L. Elizabeth Budde1, Adam J. Olszewski, MD2, Sarit Assouline, MD3, Manali Kamdar4*, Catherine S. Diefenbach, MD5, Nilanjan Ghosh, MD, PhD6, Izidore S. Lossos, MD7, Amitkumar Mehta, MD8, Waleed Sabry9*, Kathleen Dorritie, MD10, Song Pham11*, Jin Xu12*, Ling-Yuh Huw13*, Iris To13*, Yasuhiro Oki13, Carol O'Hear13 and Julio C. Chavez, MD14

1City of Hope, Duarte, CA
2Brown University, Providence, RI
3Jewish General Hospital, Montreal, QC, Canada
4University of Colorado, Aurora, CO
5Perlmutter Cancer Center at NYU Langone Health, New York, NY
6Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Atrium Health, Charlotte, NC
7Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL
8University of Alabama at Birmingham, Birmingham, AL
9Saskatoon Cancer Center, Saskatoon, SK, Canada
10O’Neal Comprehensive Cancer Center at The University of Alabama at Birmingham, Birmingham, AL
11F. Hoffmann-La Roche Ltd, Basel, Switzerland
12Roche China, Shanghai, China
13Genentech, Inc., South San Francisco, CA
14Moffitt Cancer Center, Tampa, FL

Background: Mosunetuzumab (M), a CD20xCD3 bispecific antibody, has shown durable efficacy and acceptable toxicity when given as monotherapy in patients (pts) with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) (Schuster et al. ASH 2019). An ongoing Phase Ib/II study (NCT03671018) is evaluating M in combination with the anti-CD79b antibody-drug conjugate polatuzumab vedotin (Pola; M-Pola) in pts with R/R B-NHL. In the completed Phase Ib part of the study, M-Pola had manageable toxicity and promising activity in pts with R/R B-NHL (Budde et al. ASCO 2021). We present updated results from the study, including safety and efficacy data from an ongoing Phase II expansion cohort of pts with R/R aggressive B-NHL.

Methods: The Phase Ib dose-escalation cohort enrolled pts with R/R indolent or aggressive B-NHL. The Phase II dose-expansion cohort enrolled pts with R/R aggressive B-NHL, including those with diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (trFL), and Grade (Gr) 3b FL. Treatment cycles were 21 days. Pola (1.8mg/kg IV infusion) was given on Day (D)1 of Cycle (C)1–6. M (IV infusion) was given with step-up dosing during C1 to mitigate for cytokine release syndrome (CRS), and the recommended Phase II dose (RP2D) was used (1mg on C1D1, 2mg on C1D8, 60mg on C1D15 and C2D1, and 30mg on D1 of C3–8). Pts with stable disease or a partial response (PR) at the end of C8 could continue M for a total of 17 cycles, while pts with a complete response (CR) discontinued M after C8. In the Phase II expansion cohort, mandatory hospitalization was not required for M administration. Retreatment with M or M-Pola was permitted for pts who experienced disease progression (PD) after an initial CR. Response was assessed by investigators using Lugano 2014 criteria (Cheson et al. J Clin Oncol 2014). CRS events were reported using ASTCT criteria (Lee et al. Biol Blood Marrow Transplant 2019).

Results: As of March 15, 2021, 63 pts with R/R B-NHL had been enrolled: 22 pts in the dose-escalation cohorts (n=19 with aggressive B-NHL, including 5 pts at RP2D; enrollment complete), and 41 pts in the dose-expansion cohort (all aggressive B-NHL; enrollment ongoing). Median age of all pts was 68 years (range: 20–83 years), and 62% were male; 44 pts had de novo DLBCL, 12 pts had trFL, 4 pts had Gr 3b FL, and 3 pts had Gr 1–3a FL. Four pts with aggressive B-NHL had double-hit lymphoma. Median number of prior lines of therapy was 3 (range: 1–10), and 24 pts with R/R aggressive B-NHL had received prior CAR-T therapy (dose-escalation, n=7; dose-expansion, n=17). Median duration of follow-up was 5.3 months (range: 0.7–23.7 months).

In all pts with R/R aggressive B-NHL (n=60), the objective response rate (ORR) was 65% (CR: 48%; Table). In pts with R/R de novo DLBCL (n=44), the ORR was 73% (CR: 52%). High response rates were also observed in pts with prior CAR-T therapy (ORR: 63%; CR: 42%; n=24 in dose-escalation and dose-expansion). Median duration of response (DOR) was not reached (observed DOR: 0.1+ to 15.3+ months). At data cut-off, one patient had achieved a CR with M retreatment after an initial CR that had lasted for 15 months.

The most common (≥25%) treatment-related adverse events (AEs) in all pts (n=63) were fatigue (38%), peripheral neuropathy (33%), neutropenia (33%), diarrhea (27%), and nausea (25%). The most common treatment-related (≥5%) Gr 3–4 AEs were neutropenia (21%) and fatigue (6%). Twelve deaths occurred (PD, n=9; other, n=3). One Gr 5 AE (pneumonia) was considered related to M. CRS was observed in 11 pts (18%; Gr 1 in 10 pts, Gr 2 in 1 pt), and all events occurred during C1. Median CRS duration was 1 day (range: 1–4 days). All CRS events were resolved at data cut-off, with one patient receiving corticosteroids and low-flow oxygen for the management of Gr 2 CRS; no patient received tocilizumab.

Conclusions: M-Pola shows promising efficacy and a favorable safety profile in pts with heavily pretreated R/R aggressive B-NHL, including those who have received prior CAR-T therapy. A low rate of CRS was observed, with the majority of events being Gr 1. The Phase II dose-expansion cohort continues to enroll pts with R/R aggressive B-NHL.

Disclosures: Budde: Merck: Research Funding; Amgen Inc.: Research Funding; AstraZeneca: Research Funding; Mustang Bio. Inc.: Research Funding; Novartis: Consultancy; Gilead: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy; BeiGene: Consultancy; Genentech, Inc.: Consultancy. Olszewski: Celldex Therapeutics: Research Funding; Acrotech Pharma: Research Funding; PrecisionBio: Research Funding; TG Therapeutics: Research Funding; Genentech, Inc.: Research Funding; Genmab: Research Funding. Assouline: Janssen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche/Genentech: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Eli Lilly: Research Funding; Novartis: Honoraria, Research Funding; Amgen: Current equity holder in publicly-traded company, Research Funding; Gilead: Speakers Bureau; Johnson&Johnson: Current equity holder in publicly-traded company; Jewish General Hospital, Montreal, Quebec: Current Employment. Kamdar: AbbVie: Consultancy; Karyopharm: Consultancy; Kite: Consultancy; AstraZeneca: Consultancy; Celgene/Bristol-Myers Squibb: Consultancy; Adaptive Biotechnologies: Consultancy; ADC Therapeutics: Consultancy; TG Therapeutics: Research Funding; Genentech, Inc.: Other: DMC, Research Funding; SeaGen: Speakers Bureau; Celgene: Other: DMC. Diefenbach: Trillium: Research Funding; Gilead: Current equity holder in publicly-traded company; Celgene: Research Funding; IMab: Research Funding; Incyte: Research Funding; Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding; MEI: Consultancy, Research Funding; Genentech, Inc./ F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Morphosys: Consultancy, Honoraria, Research Funding; AbbVie: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; IGM Biosciences: Research Funding; Perlmutter Cancer Center at NYU Langone Health: Current Employment. Ghosh: Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Adaptive Biotech: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; AbbVie: Honoraria, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharma: Consultancy, Honoraria; Genmab: Consultancy, Honoraria; Epizyme: Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Research Funding. Lossos: Stanford University: Patents & Royalties; NCI: Research Funding; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment. Mehta: Affirmed; Kite/Gilead; Roche-Genetech; Celgene/BMS; Oncotartis; Innate Pharmaceuticals; Seattle Genetics; Incyte; Takeda; Fortyseven Inc/Gilead; TG Therapeutics; Merck; Juno Pharmaceuticals/Bristol Myers Squibb: Research Funding; Seattle Genetics; Incyte; TG Therapeutics: Consultancy; Seattle Genetics; Incyte; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sabry: Hematologist, Saskatoon Cancer Center: Current Employment; Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Canadian Leukemia Study Group: Membership on an entity's Board of Directors or advisory committees. Dorritie: Genmab: Research Funding; Juno/BMS: Research Funding; F. Hoffman-La Roche Ltd: Research Funding; Janssen: Research Funding; OncLive/Institutional Perspectives on Cancer presentation: Honoraria; University of Pittsburgh/UPMC Hillman Cancer Center: Current Employment; Kite, a Gilead Company: Research Funding; SITC presentation: Honoraria. Pham: Roche Canada: Current Employment, Current equity holder in publicly-traded company; Institute for Clinical Evaluative Sciences: Ended employment in the past 24 months. Xu: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Huw: Genentech, Inc.: Current Employment. To: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Oki: Genentech, Inc.: Current Employment; Jazz Pharmaceuticals: Ended employment in the past 24 months. O'Hear: F. Hoffmann-La Roche Ltd: Current holder of individual stocks in a privately-held company; Genentech, Inc.: Current Employment. Chavez: MorphoSys, Bayer, Karyopharm, Kite, a Gilead Company, Novartis, Janssen, AbbVie, TeneoBio, and Pfizer: Consultancy; AstraZeneca: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Merk: Research Funding; BMS: Speakers Bureau; MorphoSys, AstraZeneca, BeiGene, Genentech, Kite, a Gilead Company, and Epizyme: Speakers Bureau.

OffLabel Disclosure: Mosunetuzumab is a CD20xCD3 bispecific antibody that redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent. Polatuzumab vedotin (Polivy) is a CD79b-directed antibody-drug conjugate indicated in combination with bendamustine and a rituximab product for the treatment of adult pts with relapsed or refractory DLBCL, not otherwise specified, after at least two prior therapies.

*signifies non-member of ASH