CD20-TCB IN RELAPSED OR REFRACTORY NON-HODGKIN LYMPHOMA: DURABLE COMPLETE RESPONSES AND MANAGEABLE SAFETY OBSERVED AT CLINICALLY RELEVANT DOSES IN PHASE I DOSE ESCALATION
Author(s): ,
Michael J Dickinson
Affiliations:
Peter MacCallum Cancer Centre, Royal Melbourne Hospital and The University of Melbourne,Melbourne, VIC,Australia
,
Franck Morschhauser
Affiliations:
Hôpital Claude Huriez and Centre Hospitalier Régional Universitaire de Lille,Lille,France
,
Gloria Iacoboni
Affiliations:
Vall d'Hebron University Hospital,Barcelona,Spain
,
Carmelo Carlo-Stella
Affiliations:
Humanitas University,Milan,Italy
,
Fritz C Offner
Affiliations:
Universitair Ziekenhuis Gent,Ghent,Belgium
,
Anna Sureda
Affiliations:
Institut Català d'Oncologia Hospitalet,Barcelona,Spain
,
Gilles Salles
Affiliations:
Hospices Civils de Lyon and Universite Claude Bernard,Pierre-Benite,France
,
Joaquin Martinez-Lopez
Affiliations:
Hospital Universitario 12 de Octubre (H12O), Centro Nacional de Investigaciones Oncológicas (CNIO)-H12O and Universidad Complutense de Madrid,Madrid,Spain
,
Michael Crump
Affiliations:
Princess Margaret Hospital,Toronto, ON,Canada
,
Linda Lundberg
Affiliations:
F. Hoffmann-La Roche Ltd.,Basel,Switzerland
,
Mark Dixon
Affiliations:
Roche Products Ltd.,Welwyn Garden City,United Kingdom
,
Antonia Kwan
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Michael C Wei
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
,
Ann-Marie E Bröske
Affiliations:
Roche Innovation Center Munich, Roche Pharma Research and Early Development,Penzberg,Germany
,
David Carlile
Affiliations:
Roche Products Ltd.,Welwyn Garden City,United Kingdom
,
Carol O'Hear
Affiliations:
Genentech, Inc.,South San Francisco, CA,United States
Martin Hutchings
Affiliations:
Rigshospitalet,Copenhagen,Denmark
EHA Library. J Dickinson M. 06/12/20; 293690; S241
Michael J Dickinson
Michael J Dickinson
Contributions
Abstract

Abstract: S241

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.


Session Title: Aggressive Lymphomas: Cellular and bispecific antibody therapies

 

Background
CD20-TCB (RG6026) is a novel T-cell-engaging bispecific antibody that comprises two fragment antigen binding (Fab) regions for CD20 (on B cells) and one Fab region for CD3 (on T cells). Due to its ‘2:1’ configuration, CD20-TCB offers the potential for increased tumor antigen avidity, rapid T-cell activation, and enhanced tumor cell killing versus other bispecific formats. NP30179 (NCT03075696) is an ongoing Phase I dose-escalation study of CD20-TCB in relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) patients (pts). Preliminary data support promising antitumor activity and manageable safety (Dickinson et al. ICML 2019).

Aims
We report data from the CD20-TCB monotherapy dose-escalation at clinically relevant doses (0.6–25mg).

Methods
In NP30179, R/R NHL pts receive 1000mg obinutuzumab on Cycle (C) 1 Day (D) −7 to mitigate for cytokine release syndrome (CRS). Pts then receive intravenous infusions of CD20-TCB in a q2w or q3w schedule for up to 12 Cs. Dose-escalation is informed by Bayesian model predictions with overdose control. Informed consent was obtained from all pts. 

Results
As of December 18, 2019, 118 pts had received CD20-TCB doses of 0.6–25mg. Aggressive NHL (aNHL) pts (n=102) were mainly DLBCL (n=68) or transformed FL (n=19); all indolent pts (n=14) were FL. Median age was 61 years (range 22–84) and median number of prior lines of therapy was 3 (1–13). Most pts (79%) were refractory to their last line of therapy and 60% were <3 months since their last therapy.

In efficacy-evaluable aNHL pts (n=96), investigator-assessed objective response (ORR) and complete response (CR) rates were 47% (45/96) and 34% (33/96), respectively (Lugano 2014). In 10–25mg pts, ORR and CR rates were 54% (32/59) and 42% (25/59), suggesting a dose-response relationship. For pts in CR, median duration of CR was not reached after a median follow-up of 7.1 months, with 25/33 (76%) pts maintaining their CR. In efficacy-evaluable FL pts (n=13), the ORR/CR rate was 77% (10/13) in all pts and 88% (7/8) in 10–16mg pts. For pts in CR, median duration of response was not reached after a median follow-up of 2.8 months, with 9/10 (90%) pts maintaining their CR. Responses to CD20-TCB were seen across all NHL subtypes and approximately equally across prognostic factors such as disease burden, prior lines of therapy, and refractoriness to prior therapy. CR was usually achieved early, at the first or second response assessments (C3 or C6).

Common (>30% of pts) adverse events were CRS (n=65, 55.1%), pyrexia (n=41, 34.7%), and neutropenia (n=41, 34.7%). Most CRS events (Lee et al. Blood 2014) were Grade (Gr) 1 (n=26, 22%) or Gr 2 (n=36; 31%); Gr 3 and Gr 4 events were uncommon (n=1 each; missing Gr, n=1). Most CRS events were associated with the first dose and were manageable, and the majority of events had resolved by data cut-off. For any Gr CRS events, a dose-response relationship was observed with the q2w and q3w schedule. CD20-TCB exposure increased in a dose-dependent manner and half-life was in the range of 5–10 days. Average CD20-TCB receptor occupancy (AvgRO%) on D1 was associated with safety (Gr ≥2 CRS) and CD20-TCB AvgRO% up to C3 D1 was associated with efficacy (ORR and CR). Mode of action was demonstrated by rapid and sustained T-cell activation in peripheral blood and tumor biopsies.

 

Conclusion
CD20-TCB shows strong clinical efficacy, including durable CRs, and manageable safety in heavily-pretreated NHL pts. Updated safety, efficacy, PK and biomarker data will be presented.

 

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

Keyword(s): B cell lymphoma, Cancer immunotherapy, CAR-T, CD20



Abstract: S241

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.


Session Title: Aggressive Lymphomas: Cellular and bispecific antibody therapies

 

Background
CD20-TCB (RG6026) is a novel T-cell-engaging bispecific antibody that comprises two fragment antigen binding (Fab) regions for CD20 (on B cells) and one Fab region for CD3 (on T cells). Due to its ‘2:1’ configuration, CD20-TCB offers the potential for increased tumor antigen avidity, rapid T-cell activation, and enhanced tumor cell killing versus other bispecific formats. NP30179 (NCT03075696) is an ongoing Phase I dose-escalation study of CD20-TCB in relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) patients (pts). Preliminary data support promising antitumor activity and manageable safety (Dickinson et al. ICML 2019).

Aims
We report data from the CD20-TCB monotherapy dose-escalation at clinically relevant doses (0.6–25mg).

Methods
In NP30179, R/R NHL pts receive 1000mg obinutuzumab on Cycle (C) 1 Day (D) −7 to mitigate for cytokine release syndrome (CRS). Pts then receive intravenous infusions of CD20-TCB in a q2w or q3w schedule for up to 12 Cs. Dose-escalation is informed by Bayesian model predictions with overdose control. Informed consent was obtained from all pts. 

Results
As of December 18, 2019, 118 pts had received CD20-TCB doses of 0.6–25mg. Aggressive NHL (aNHL) pts (n=102) were mainly DLBCL (n=68) or transformed FL (n=19); all indolent pts (n=14) were FL. Median age was 61 years (range 22–84) and median number of prior lines of therapy was 3 (1–13). Most pts (79%) were refractory to their last line of therapy and 60% were <3 months since their last therapy.

In efficacy-evaluable aNHL pts (n=96), investigator-assessed objective response (ORR) and complete response (CR) rates were 47% (45/96) and 34% (33/96), respectively (Lugano 2014). In 10–25mg pts, ORR and CR rates were 54% (32/59) and 42% (25/59), suggesting a dose-response relationship. For pts in CR, median duration of CR was not reached after a median follow-up of 7.1 months, with 25/33 (76%) pts maintaining their CR. In efficacy-evaluable FL pts (n=13), the ORR/CR rate was 77% (10/13) in all pts and 88% (7/8) in 10–16mg pts. For pts in CR, median duration of response was not reached after a median follow-up of 2.8 months, with 9/10 (90%) pts maintaining their CR. Responses to CD20-TCB were seen across all NHL subtypes and approximately equally across prognostic factors such as disease burden, prior lines of therapy, and refractoriness to prior therapy. CR was usually achieved early, at the first or second response assessments (C3 or C6).

Common (>30% of pts) adverse events were CRS (n=65, 55.1%), pyrexia (n=41, 34.7%), and neutropenia (n=41, 34.7%). Most CRS events (Lee et al. Blood 2014) were Grade (Gr) 1 (n=26, 22%) or Gr 2 (n=36; 31%); Gr 3 and Gr 4 events were uncommon (n=1 each; missing Gr, n=1). Most CRS events were associated with the first dose and were manageable, and the majority of events had resolved by data cut-off. For any Gr CRS events, a dose-response relationship was observed with the q2w and q3w schedule. CD20-TCB exposure increased in a dose-dependent manner and half-life was in the range of 5–10 days. Average CD20-TCB receptor occupancy (AvgRO%) on D1 was associated with safety (Gr ≥2 CRS) and CD20-TCB AvgRO% up to C3 D1 was associated with efficacy (ORR and CR). Mode of action was demonstrated by rapid and sustained T-cell activation in peripheral blood and tumor biopsies.

 

Conclusion
CD20-TCB shows strong clinical efficacy, including durable CRs, and manageable safety in heavily-pretreated NHL pts. Updated safety, efficacy, PK and biomarker data will be presented.

 

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

Keyword(s): B cell lymphoma, Cancer immunotherapy, CAR-T, CD20


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