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SUBCUTANEOUS EPCORITAMAB (GEN3013; CD3XCD20) IN PATIENTS WITH RELAPSED/REFRACTORY B-CELL NON-HODGKIN LYMPHOMA: DOSE-ESCALATION DATA FROM A PHASE 1/2 TRIAL
Author(s): ,
Martin Hutchings
Affiliations:
Rigshospitalet,Copenhagen,Denmark
,
Peter Johnson
Affiliations:
Cancer Research UK Centre,Southampton,United Kingdom
,
Rogier Mous
Affiliations:
University Medical Center Utrecht, on behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC,Utrecht,Netherlands
,
Michael Roost Clausen
Affiliations:
Vejle Hospital,Vejle,Denmark
,
Martine Chamuleau
Affiliations:
VU University Medical Center on behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC,Amsterdam,Netherlands
,
Kim Linton
Affiliations:
Christie Hospital,Manchester,United Kingdom
,
Simon Rule
Affiliations:
Plymouth University Medical School,Plymouth,United Kingdom
,
Juanita Lopez
Affiliations:
The Royal Marsden Hospital,London,United Kingdom
,
Roberto S Oliveri
Affiliations:
Genmab,Copenhagen,Denmark
,
Dena DeMarco
Affiliations:
Genmab,Princeton,United States
,
Brian Elliott
Affiliations:
Genmab,Princeton,United States
Pieternella Lugtenburg
Affiliations:
Erasmus MC Cancer Institute, on behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC,Rotterdam,Netherlands
(Abstract release date: 05/14/20) EHA Library. Hutchings M. 06/12/20; 293707; EP1218
Dr. Martin Hutchings
Dr. Martin Hutchings
Contributions
Abstract

Abstract: EP1218

Type: e-Poster

Background
CD20-specific monoclonal antibodies (mAbs) have demonstrated efficacy in combination therapy for the treatment of B-cell non-Hodgkin lymphoma (B-NHL); however, most patients relapse or become refractory (R/R). CD3xCD20 bispecific antibodies (bsAbs) have shown promising results in patients with R/R B-NHL. Epcoritamab (GEN3013), a novel, subcutaneously administered CD3xCD20 bsAb, has a favorable safety profile and encouraging preliminary antitumor activity at low doses in patients with aggressive and indolent B-NHL. Here, we present dose-escalation data from the ongoing first-in-human trial (NCT03625037).

Aims
The primary objectives are to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). A key secondary objective is to evaluate antitumor activity.

Methods
Adults with R/R CD20+ B-NHL, previously treated with anti-CD20 mAb, received a single subcutaneous injection of flat-dose epcoritamab in 28-day cycles (q1w: cycle 1–2; q2w: cycle 3–6; q4w thereafter) until disease progression or unacceptable toxicity. Risk mitigation for cytokine release syndrome (CRS) included use of corticosteroids and priming and/or intermediate doses of epcoritamab.

Results
As of January 8, 2020, 41 patients with a median age of 66 (range: 21–82) years were enrolled. Most patients had ECOG PS 0–1 (98%) and diffuse large B-cell lymphoma (DLBCL; de novo DLBCL: 29%; transformed DLBCL: 34%); 20% had follicular lymphoma (FL) and 7% had high-grade B-cell lymphoma (HGBCL). Patients had received a median of 3 (range: 1–18) prior lines of treatment, including CD20 mAb (100%), alkylating agents (98%), and anthracyclines (88%). Most patients were refractory to their most recent systemic therapy (66%), anti-CD20 mAb (any line: 61%; last line: 54%), and/or alkylating agents (61%). At a median follow-up of 4.7 (range: 3.7–5.6) months, no dose-limiting toxicities (DLTs) have been observed. MTD has not been reached. The most common (>35%) treatment-emergent adverse events (TEAEs) were pyrexia (71%), fatigue (46%), and injection site reaction (39%). TEAEs of special interest included CRS (59%; all Grade 1/2 and resolved) and cytokine release-related decreased cognitive CARTOX-10 score (n=1). There were no clinical tumor lysis syndrome events or treatment-related deaths. Treatment is ongoing in 13 patients. Antitumor activity against DLBCL/HGBCL and FL at doses above 0.76-mg cutoff, based on minimal efficacy threshold and supported by pharmacokinetic modeling, is shown in the Table. Updated dose-escalation data and RP2D will be presented.

Conclusion
Epcoritamab administered subcutaneously continues to demonstrate a favorable safety profile across all doses, with no severe or life-threatening CRS events and no DLTs. Dose-escalation data show improved efficacy as doses reach above the modeled predicted efficacy threshold, inducing complete response (CR) in heavily pretreated patients with DLBCL. These responses appear to be durable as all patients achieving CR remain in remission.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Antibody, B cell lymphoma, Immunotherapy, Lymphoma

Abstract: EP1218

Type: e-Poster

Background
CD20-specific monoclonal antibodies (mAbs) have demonstrated efficacy in combination therapy for the treatment of B-cell non-Hodgkin lymphoma (B-NHL); however, most patients relapse or become refractory (R/R). CD3xCD20 bispecific antibodies (bsAbs) have shown promising results in patients with R/R B-NHL. Epcoritamab (GEN3013), a novel, subcutaneously administered CD3xCD20 bsAb, has a favorable safety profile and encouraging preliminary antitumor activity at low doses in patients with aggressive and indolent B-NHL. Here, we present dose-escalation data from the ongoing first-in-human trial (NCT03625037).

Aims
The primary objectives are to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). A key secondary objective is to evaluate antitumor activity.

Methods
Adults with R/R CD20+ B-NHL, previously treated with anti-CD20 mAb, received a single subcutaneous injection of flat-dose epcoritamab in 28-day cycles (q1w: cycle 1–2; q2w: cycle 3–6; q4w thereafter) until disease progression or unacceptable toxicity. Risk mitigation for cytokine release syndrome (CRS) included use of corticosteroids and priming and/or intermediate doses of epcoritamab.

Results
As of January 8, 2020, 41 patients with a median age of 66 (range: 21–82) years were enrolled. Most patients had ECOG PS 0–1 (98%) and diffuse large B-cell lymphoma (DLBCL; de novo DLBCL: 29%; transformed DLBCL: 34%); 20% had follicular lymphoma (FL) and 7% had high-grade B-cell lymphoma (HGBCL). Patients had received a median of 3 (range: 1–18) prior lines of treatment, including CD20 mAb (100%), alkylating agents (98%), and anthracyclines (88%). Most patients were refractory to their most recent systemic therapy (66%), anti-CD20 mAb (any line: 61%; last line: 54%), and/or alkylating agents (61%). At a median follow-up of 4.7 (range: 3.7–5.6) months, no dose-limiting toxicities (DLTs) have been observed. MTD has not been reached. The most common (>35%) treatment-emergent adverse events (TEAEs) were pyrexia (71%), fatigue (46%), and injection site reaction (39%). TEAEs of special interest included CRS (59%; all Grade 1/2 and resolved) and cytokine release-related decreased cognitive CARTOX-10 score (n=1). There were no clinical tumor lysis syndrome events or treatment-related deaths. Treatment is ongoing in 13 patients. Antitumor activity against DLBCL/HGBCL and FL at doses above 0.76-mg cutoff, based on minimal efficacy threshold and supported by pharmacokinetic modeling, is shown in the Table. Updated dose-escalation data and RP2D will be presented.

Conclusion
Epcoritamab administered subcutaneously continues to demonstrate a favorable safety profile across all doses, with no severe or life-threatening CRS events and no DLTs. Dose-escalation data show improved efficacy as doses reach above the modeled predicted efficacy threshold, inducing complete response (CR) in heavily pretreated patients with DLBCL. These responses appear to be durable as all patients achieving CR remain in remission.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Antibody, B cell lymphoma, Immunotherapy, Lymphoma

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