Bispecific Antibody REGN1979 Shows Promising Efficacy in Relapsed/Refractory Non-Hodgkin Lymphomas

In a small phase I study of patients with relapsed/refractory non-Hodgkin lymphoma (NHL), approximately half of patients responded to treatment with REGN1979, an anti-CD20 and anti-CD3 bispecific antibody. The agent also demonstrated high response rates in other disease subtypes, according to lead author Rajat Bannerji, MD, PhD, from Rutgers Cancer Institute of New Jersey, who presented these results at the 24th Congress of the European Hematology Association.

The study evaluated the safety and potential efficacy of REGN1979 in patients with relapsed/refractory NHL who had previously received at least one CD20-directed therapy, plus standard chemotherapy.

Per study protocol, REGN1979 was administered over a 36-week period: First, patients received 12 weekly doses of REGN1979 delivered intravenously, followed by REGN1979 every two weeks for a total of 12 doses.

At the time of data cutoff (December 6, 2018), 71 patients had been treated with REGN1979, at doses ranging from 0.03 mg to 80 mg. Participants received a median of nine doses (range = 1-24). Diagnoses included:

  • diffuse large B-cell lymphoma (DLBCL) (n=39)
  • FL grade 1-3a (n=17)
  • other (mantle cell lymphoma, marginal zone lymphoma, FL grade 3b, FL unknown/ungraded, or Waldenström macroglobulinemia; n=15)

Forty-six patients discontinued treatment early (mostly due to progressive disease [n=29]), leaving 10 patients on treatment and 15 patients who completed treatment.

The investigators did not observe any dose-limiting toxicities, and the most common treatment-emergent adverse events (AEs) included:

  • 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 patients experienced grade ≥3 CRS, but their severity reduced with adjustments to premedication before administration of REGN1979. No seizure and/or encephalopathy was reported, and no neurologic event required treatment termination, they added.

Other common grade ≥3 AEs included:

  • neutropenia (n=14)
  • lymphopenia (n=14)
  • anemia (n=12)
  • thrombocytopenia (n=8)

Four patients experienced AEs that led to treatment discontinuation (grade 3 hemolysis, grade 3 fatigue, grade 3 pneumonia, and grade 3 neck abscess). Nine patients died during follow-up, mostly related to progressive disease (n=6), followed by gastric perforation (n=1), cardiac arrest (n=1), and lung infection (n=1).

REGN1979 showed the highest degree of efficacy in the 17 patients with relapsed/refractory grade 1–3a FL. At dose levels ≥5 mg, the agent produced an overall response rate (ORR) of 100%. This included eight patients with a complete response and two with a partial response.

Benefit also was observed in patients with DLBCL and appeared to increase with higher doses, with ORRs ranging from 18.2% in the 5- to 12-mg dosing cohort to 100% in the 80-mg dosing cohort.

While the researchers reported increased serum cytokine levels with higher REGN1979 doses, there was no association between these elevated levels and clinical efficacy. “Relapse among responders was seen with either maintenance or loss of CD20 expression, suggesting antigen-dependent and independent disease escape mechanisms,” the investigators added.

Dr. Bannerji noted that the next steps for REGN1979 will be to determine its activity in defined FL, DLBCL and other B-cell NHL subtypes in subsequent phase II studies. “With the caveat that we are very early in development, we believe that REGN1979 offers an ‘off-the-shelf’ T cell–activating immunotherapy with the potential to be combined with other active therapies for the treatment of B-cell lymphomas,” he told ASH Clinical News.

Limitations of this analysis include the small sample size, the lack of a comparator arm, and the lack of information about response duration.

The authors report relationships with Regeneron Pharmaceuticals, which sponsored the study.

Reference

Bannerji R, Arnason J, Advani R, et al. Emerging clinical activity of REGN1979, an anti-CD20 X anti-CD3 bispecific antibody (AB), in patients (PTS) with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Abstract #S868. Presented at the 24th European Hematology Association Annual Congress, June 15, 2019; Amsterdam, The Netherlands.

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