Abstract: S868

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 16:30 - 16:45

Location: Hall 5

Background
REGN1979 is an anti-CD20 x anti-CD3 bispecific IgG4 Ab. We report updated results of a Phase 1 trial of REGN1979 in pts with R/R B-NHL previously treated with anti-CD20 Abs and chemotherapy.

Aims
Primary objectives are to determine safety, tolerability, and occurrence of dose limiting toxicities (DLTs). Other objectives are to assess antitumor activity, pharmacokinetics (PK), and pharmacodynamics.

Methods
Eligible pts with R/R B-NHL must have received at least 1 prior CD20-directed therapy with standard chemotherapy. Treatment consists of 12 weekly intravenous doses of REGN1979 followed by every 2-week dosing for 12 doses (total of 36 weeks).

Results
As of Dec 6, 2018, 71 pts (diffuse large cell B-cell lymphoma [DLBCL] [n=39], follicular lymphoma [FL] grade [Gr] 1-3a  [n=17], other [mantle cell lymphoma {MCL}, marginal zone lymphoma {MZL}, FL grade 3b, FL unknown/ungraded, or Waldenstrom macroglobulinemia {WM} [n=15]) were treated with REGN1979 0.03–80 mg and received a median of 9 doses (range 1–24). Ten pts remain on treatment; 15 completed treatment; 46 discontinued early (29 due to progressive disease [PD]).

No patients with B-NHL experienced a DLT. Most common treatment-emergent adverse events (AEs) were pyrexia (n=56), chills (n=38), cytokine release syndrome (CRS; n=37), fatigue (n=26), increased C-reactive protein (n=24), anemia (n=23). Four pts experienced Gr ≥3 CRS. The severity of CRS symptoms declined through optimized pre-medication even with REGN1979 dose escalation. Most common Gr ≥3 AEs were decreased neutrophils/neutropenia (n=14), decreased lymphocytes/lymphopenia (n=14), anemia (n=12), platelet count decreased/thrombocytopenia (n=8). No seizure and/or encephalopathy was reported, and no neurological event required treatment termination. Four pts discontinued due to AEs: Gr 3 hemolysis; Gr 3 fatigue; Gr 3 pneumonia; and Gr 3 neck abscess (1 each). Nine pts died on study: PD (n=6), gastric perforation (n=1), cardiac arrest (n=1), lung infection (n=1).

The Table and Figure show efficacy and duration of follow-up by R/R B-NHL subtype and dose level. Treatment with REGN1979 at all doses ≥5mg has shown marked efficacy in R/R FL Gr 1–3a (ORR: 100% [10/10 OR; 8/10 CR; 2/10 PR]), while increasing efficacy is observed in patients with R/R DLBCL (and other B-NHL subtypes) as the dose is further increased; of note, in patients with R/R DLBCL, 2/11 (18%) had responses at doses between 5-12mg, 6/11 (55%) had responses at doses between 18-40mg, and 2/2 (100%) had responses at the 80mg dose, with both of these latter being CRs.

REGN1979 concentrations in serum increased linearly with dose. Elevated levels of serum cytokines were observed with dosing; however, no correlation was observed with clinical efficacy. Immunohistological analysis of malignant lymph node tissue demonstrated that pts with high and low CD20 achieved clinical response. Relapse among responders was seen with either maintenance or loss of CD20 expression, suggesting antigen-dependent and independent disease escape mechanisms.

Conclusion

REGN1979 was well tolerated in pts with R/R B-NHL. No DLTs and no significant neurological toxicity were observed. Treatment with REGN1979 showed impressive efficacy with a 100% ORR in R/R FL starting at doses above 5mg. With increasing doses, more resistant tumors such as R/R DLBCL are showing benefit, approaching the ORR seen with R/R FL at 80 mg. Based on these efficacy findings, a phase 2 study testing a selected dose in R/R FL Gr 1-3a, R/R DLBCL, and other R/R B-NHL subtypes is planned.

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

Keyword(s): Antibody, Lymphoma