Anti-CD79B Antibody–Drug Conjugate DCDS0780A in Patients with B-Cell Non-Hodgkin Lymphoma: Phase 1 Dose-Escalation Study

Author:

Herrera Alex F.1,Patel Manish R.2ORCID,Burke John M.3ORCID,Advani Ranjana4,Cheson Bruce D.5ORCID,Sharman Jeff P.6ORCID,Penuel Elicia7,Polson Andrew G.7,Liao Chen Di8,Li Chunze7,Schuth Eva7,Vaze Anjali7,Samineni Divya7,Elstrom Rebecca7,Cooper James7,Diefenbach Catherine9

Affiliation:

1. 1City of Hope Medical Center, Duarte, California.

2. 2Sarah Cannon Research Institute and Florida Cancer Specialists, Sarasota, Florida.

3. 3US Oncology and Rocky Mountain Cancer Centers, Aurora, Colorado.

4. 4Stanford Cancer Center, Stanford, California.

5. 5Georgetown University Hospital, Washington, DC.

6. 6US Oncology and Willamette Valley Cancer Institute, Springfield, Oregon.

7. 7Genentech, Inc., South San Francisco, California.

8. 8Hoffmann-La Roche Limited, Mississauga, Ontario, Canada.

9. 9NYU Langone School of Medicine/NYU Perlmutter Cancer Center, New York, New York.

Abstract

Abstract Purpose: Targeting CD79B using antibody–drug conjugates (ADC) is an effective therapeutic strategy in B-cell non-Hodgkin lymphoma (B-NHL). We investigated DCDS0780A, an anti-CD79B ADC with THIOMAB technology (TDC) that consistently conjugates two anti-neoplastic molecules per antibody, in contrast with ADCs with heterogeneous loads. Patients and Methods: This phase 1 study enrolled 60 patients with histologically confirmed B-NHL that had relapsed/failed to respond following ≥1 prior treatment regimens; 41 (68%) had diffuse large B-cell lymphoma (DLBCL). Fifty-one patients received DCDS0780A monotherapy once every 3 weeks (0.3–4.8 mg/kg); 9 received combination therapy (3.6–4.8 mg/kg) with rituximab. Results: Fifty-four (90%) patients experienced adverse events related to study drug, the most common of which were blurred vision, fatigue, corneal deposits, neutropenia, nausea, and peripheral neuropathy. 4.8 mg/kg was the highest dose tested and the recommended phase II dose. The pharmacokinetic profile was linear at doses ≥1.2 mg/kg. Response rate in all-treated patients (N = 60) was 47% (n = 28), including 17 complete responses (28%) and 11 partial responses (18%). The median duration of response (15.2 months) was the same for all responders (n = 28) and patients with DLBCL (n = 20). Conclusions: DCDS0780A as the TDC format for CD79B was tested at higher doses than its ADC counterpart investigated earlier, leading to deep responses. However, dose intensity was limited by ocular toxicities seen at the higher doses indicating that the TDC format was unable, in the current study, to expand the therapeutic index for the CD79B target. The encouraging antitumor activity advocates continuation of investigations into novel ADC technologies.

Funder

NIH

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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