Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial
Catherine Thieblemont, Tycel Phillips, Herve Ghesquieres, Chan Y Cheah, Michael Roost Clausen, David Cunningham, Young Rok Do, Tatyana Feldman, Robin Gasiorowski, Wojciech Jurczak, Tae Min Kim, David John Lewis, Marjolein van der Poel, Michelle Limei Poon, Mariana Cota Stirner, Nurgul Kilavuz, Christopher Chiu, Menghui Chen, Mariana Sacchi, Brian Elliott, Tahamtan Ahmadi, Martin Hutchings, Pieternella J Lugtenburg, Catherine Thieblemont, Tycel Phillips, Herve Ghesquieres, Chan Y Cheah, Michael Roost Clausen, David Cunningham, Young Rok Do, Tatyana Feldman, Robin Gasiorowski, Wojciech Jurczak, Tae Min Kim, David John Lewis, Marjolein van der Poel, Michelle Limei Poon, Mariana Cota Stirner, Nurgul Kilavuz, Christopher Chiu, Menghui Chen, Mariana Sacchi, Brian Elliott, Tahamtan Ahmadi, Martin Hutchings, Pieternella J Lugtenburg
Abstract
Purpose: Epcoritamab is a subcutaneously administered CD3xCD20 T-cell-engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20+ B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes.
Patients and methods: In the dose-expansion cohort of a phase I/II study (ClinicalTrials.gov identifier: NCT03625037), adults with relapsed or refractory CD20+ large B-cell lymphoma and at least two prior therapy lines (including anti-CD20 therapies) received subcutaneous epcoritamab in 28-day cycles (once weekly step-up doses in weeks 1-3 of cycle 1, then full doses once weekly through cycle 3, once every 2 weeks in cycles 4-9, and once every 4 weeks in cycle 10 and thereafter) until disease progression or unacceptable toxicity. The primary end point was overall response rate by the independent review committee.
Results: As of January 31, 2022, 157 patients were treated (median age, 64 years [range, 20-83]; median of three [range, 2-11] prior therapy lines; primary refractory disease: 61.1%; prior chimeric antigen receptor (CAR) T-cell exposure: 38.9%). At a median follow-up of 10.7 months, the overall response rate was 63.1% (95% CI, 55.0 to 70.6) and the complete response rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and complete response rates were similar across key prespecified subgroups. The most common treatment-emergent adverse events were cytokine release syndrome (49.7%; grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). Immune effector cell-associated neurotoxicity syndrome occurred in 6.4% of patients with one fatal event.
Conclusion: Subcutaneous epcoritamab resulted in deep and durable responses and manageable safety in highly refractory patients with large B-cell lymphoma, including those with prior CAR T-cell exposure.
Conflict of interest statement
Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell–Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II TrialThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Catherine ThieblemontHonoraria: Celgene, AbbVie, Bayer, Janssen, Roche, Incyte, Novartis, Gilead Sciences
Research Funding: Roche
Travel, Accommodations, Expenses: Roche, Janssen-Cilag, Kite/Gilead, Novartis, AbbVie
Tycel PhillipsHonoraria: Seattle Genetics, Lymphoma & Myeloma Connect
Consulting or Advisory Role: Seattle Genetics, Pharmacyclics, Incyte, Genentech, Bayer, Gilead Sciences, Curis, Kite/Gilead, Celgene, Genmab, TG Therapeutics, ADC Therapeutics, Lilly
Research Funding: AbbVie, Pharmacyclics/Janssen, Bayer, Genentech
Herve GhesquieresHonoraria: Gilead Sciences, Roche, Takeda
Consulting or Advisory Role: Gilead Sciences, Roche
Travel, Accommodations, Expenses: AbbVie
Chan Y. CheahHonoraria: Roche/Genentech, Janssen-Cilag, TG Therapeutics, Loxo/Lilly, AstraZeneca, Bristol Myers Squibb, Gilead Sciences, BeiGene, Novartis
Consulting or Advisory Role: Janssen-Cilag, Roche/Genentech (Inst), TG Therapeutics, Loxo/Lilly, Gilead Sciences, AstraZeneca, Bristol Myers Squibb, Ascentage Pharma, Merck
Research Funding: Roche/Genentech (Inst), Bristol Myers Squibb (Inst), AbbVie (Inst), Merck (Inst)
Travel, Accommodations, Expenses: Roche
Michael Roost ClausenConsulting or Advisory Role: AbbVie, Janssen, Kite, a Gilead company, Genmab
Speakers' Bureau: AbbVie, Janssen
Travel, Accommodations, Expenses: AstraZeneca/Merck, Janssen, Genmab, AbbVie
David CunninghamStock and Other Ownership Interests: OVIBIO
Consulting or Advisory Role: OVIBIO
Research Funding: Celgene (Inst), MedImmune (Inst), Bayer (Inst), 4SC (Inst), Clovis Oncology (Inst), Lilly (Inst), Roche (Inst), Leap Oncology (Inst)
Tatyana FeldmanHonoraria: Seattle Genetics, Pharmacyclics/Janssen, AbbVie, Bristol Myers Squibb, Kite, a Gilead company, Bayer, Takeda
Consulting or Advisory Role: Seattle Genetics, Bristol Myers Squibb, Genmab, ADC Therapeutics, AstraZeneca
Speakers' Bureau: Seattle Genetics, Kite, a Gilead company
Research Funding: Bristol Myers Squibb (Inst), Seattle Genetics (Inst), Portola Pharmaceuticals (Inst), Eisai (Inst), Kyowa Hakko Kirin (Inst), Amgen (Inst), Viracta Therapeutics (Inst), Cell Medica (Inst), Roche (Inst), Trillium Therapeutics (Inst), Pfizer (Inst)
Travel, Accommodations, Expenses: Seattle Genetics, Takeda
Robin GasiorowskiHonoraria: MSD, AbbVie, Astellas Pharma, Janssen, Novartis, Otsuka
Wojciech JurczakConsulting or Advisory Role: Roche, AstraZeneca, BeiGene
Research Funding: Acerta Pharma, TG Therapeutics, Sandoz-Novartis, Roche, Takeda, Epizyme, Janssen-Cilag, BeiGene, MorphoSys, MEI Pharma
Tae Min KimConsulting or Advisory Role: Hanmi, AstraZeneca/MedImmune, Janssen Oncology, Novartis, Takeda, Yuhan
Speakers' Bureau: Takeda, Roche/Genentech
Research Funding: AstraZeneca
Uncompensated Relationships: AstraZeneca/MedImmune, Novartis, Bayer, Sanofi, Boryung, Roche/Genentech
David John LewisConsulting or Advisory Role: Janssen Oncology, Kite/Gilead, BeiGene
Travel, Accommodations, Expenses: Kite, a Gilead company
Marjolein van der PoelConsulting or Advisory Role: Takeda
Travel, Accommodations, Expenses: Jazz Pharmaceuticals, Daiichi Sankyo, AbbVie
Mariana Cota StirnerEmployment: AbbVie
Stock and Other Ownership Interests: AbbVie
Travel, Accommodations, Expenses: AbbVie
Nurgul KilavuzEmployment: ADC Therapeutics, Genmab
Stock and Other Ownership Interests: Bristol Myers Squibb/Celgene, Genmab, ADC Therapeutics
Christopher ChiuEmployment: Janssen Research & Development, Genmab
Stock and Other Ownership Interests: Genmab
Patents, Royalties, Other Intellectual Property: Related to Daratumumab with Janssen, Related to Epcoritamab with Genmab
Menghui ChenEmployment: Genmab, Janssen
Stock and Other Ownership Interests: Genmab, Merck/Schering Plough
Mariana SacchiEmployment: Genmab
Leadership: Genmab
Stock and Other Ownership Interests: Genmab
Brian ElliottEmployment: Genmab, Novartis
Stock and Other Ownership Interests: Novartis, Genmab
Patents, Royalties, Other Intellectual Property: Patents pending related to Genmab development of epcoritamab
Travel, Accommodations, Expenses: Genmab, Novartis
Tahamtan AhmadiEmployment: Genmab
Leadership: Genmab
Stock and Other Ownership Interests: Genmab
Martin HutchingsConsulting or Advisory Role: Takeda, Roche, Genmab, Janssen, AbbVie
Research Funding: Celgene (Inst), Genmab (Inst), Roche (Inst), Takeda (Inst), Novartis (Inst), Janssen (Inst), Merck (Inst), AbbVie (Inst), AstraZeneca (Inst)
Pieternella J. LugtenburgConsulting or Advisory Role: Takeda, Roche/Genentech, Genmab, Celgene, Regeneron, Incyte, AbbVie, Y-mAbs Therapeutics
Research Funding: Takeda (Inst), Servier (Inst)
Travel, Accommodations, Expenses: Celgene
No other potential conflicts of interest were reported.
Figures
References
- Swerdlow SH, Campo E, Pileri SA, et al. : The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127:2375-2390, 2016
- Wienand K, Chapuy B: Molecular classification of aggressive lymphomas-past, present, future. Hematol Oncol 39:24-30, 2021
- Crump M, Neelapu SS, Farooq U, et al. : Outcomes in refractory diffuse large B-cell lymphoma: Results from the international SCHOLAR-1 study. Blood 130:1800-1808, 2017
- Myers GD, Verneris MR, Goy A, et al. : Perspectives on outpatient administration of CAR-T cell therapy in aggressive B-cell lymphoma and acute lymphoblastic leukemia. J Immunother Cancer 9:e002056, 2021
- Bhaskar ST, Dholaria BR, Sengsayadeth SM, et al. : Role of bridging therapy during chimeric antigen receptor T cell therapy. eJHaem 3:39-45, 2022
- Engelberts PJ, Hiemstra IH, de Jong B, et al. : DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine 52:102625, 2020
- van der Horst HJ, de Jonge AV, Hiemstra IH, et al. : Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. Blood Cancer J 11:38, 2021
- Hutchings M, Mous R, Clausen MR, et al. : Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: An open-label, phase 1/2 study. Lancet 398:1157-1169, 2021
- Cheson BD, Fisher RI, Barrington SF, et al. : Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano classification. J Clin Oncol 32:3059-3067, 2014
- Lee DW, Santomasso BD, Locke FL, et al. : ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 25:625-638, 2019
- Coiffier B, Altman A, Pui CH, et al. : Guidelines for the management of pediatric and adult tumor lysis syndrome: An evidence-based review. J Clin Oncol 26:2767-2778, 2008
- Schuster SJ, Bishop MR, Tam CS, et al. : Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 380:45-56, 2019
- Abramson JS, Palomba ML, Gordon LI, et al. : Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet 396:839-852, 2020
- Neelapu SS, Locke FL, Bartlett NL, et al. : Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 377:2531-2544, 2017
- Sehn LH, Salles G: Diffuse large B-cell lymphoma. N Engl J Med 384:842-858, 2021
- Di Blasi R, Le Gouill S, Bachy E, et al. : Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: A DESCAR-T analysis. Blood 140:2584-2593, 2022
- Sehn LH, Herrera AF, Flowers CR, et al. : Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 38:155-165, 2020
- Smith SD, Lopedote P, Samara Y, et al. : Polatuzumab vedotin for relapsed/refractory aggressive B-cell lymphoma: A multicenter post-marketing analysis. Clin Lymphoma Myeloma Leuk 21:170-175, 2021
- Salles G, Duell J, González Barca E, et al. : Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): A multicentre, prospective, single-arm, phase 2 study. Lancet Oncol 21:978-988, 2020
- Kalakonda N, Maerevoet M, Cavallo F, et al. : Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): A single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol 7:e511-e522, 2020
- Caimi PF, Ai W, Alderuccio JP, et al. : Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): A multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 22:790-800, 2021
- Nowakowski GS, Yoon DH, Peters A, et al. : Improved efficacy of tafasitamab plus lenalidomide versus systemic therapies for relapsed/refractory DLBCL: RE-MIND2, an observational retrospective matched cohort study. Clin Cancer Res 28:4003-4017, 2022
- Budde LE, Assouline S, Sehn LH, et al. : Single-agent mosunetuzumab shows durable complete responses in patients with relapsed or refractory B-cell lymphomas: phase I dose-escalation study. J Clin Oncol 40:481-491, 2022
- Hutchings M, Morschhauser F, Iacoboni G, et al. : Glofitamab, a novel, bivalent CD20-targeting T-cell–engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial. J Clin Oncol 39:1959-1970, 2021
- Dickinson M, Carlo-Stella C, Morschhauser F, et al. : Glofitamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and ≥2 prior therapies: Pivotal phase II expansion results. J Clin Oncol 40, 2022. (suppl 16; abstr 7500)
- Bannerji R, Arnason JE, Advani RH, et al. : Odronextamab, a human CD20×CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): Results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Lancet Haematol 9:e327-e339, 2022
Source: PubMed