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ePoster Display Session

20P - IGN002 (antiCD20-IFNα2b) intravenously administered tumour targeted delivery of IFNα2b and its effects in non-Hodgkin lymphoma

Date

01 Mar 2021

Session

ePoster Display Session

Presenters

Sribalaji Lakshmikanthan

Citation

Annals of Oncology (2021) 32 (suppl_1): S9-S13. 10.1016/annonc/annonc458

Authors

S. Lakshmikanthan1, P.S. Kolli1, M. Tugnait1, J. Dalsing-Hernandez2, D. Diaz2, P. Gonzales2, J.A. Barrett1

Author affiliations

  • 1 Preclinical Translational Medicine, Spectrum Pharmaceuticals, 92618 - Irvine/US
  • 2 Nonclinical Operations, Translational Drug Development, 85259 - Scottsdale/US
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Abstract 20P

Background

IFNα2b elicits potent anti-tumor antiproliferative and immunostimulatory activity; but with systemic toxicity. Delivering IFNα2b targeted to CD20+ lymphomas may lower systemic toxicity and increase therapeutic index. IGN002 is a novel recombinant protein comprised of anti-CD20 antibody (rituximab) fused to human IFNα2b by a peptide linker. Here, we report IGN002 stability in serum and tumor as well as efficacy in vivo in a B-cell non-Hodgkin lymphoma (NHL) xenograft model.

Methods

SCID mice bearing subcutaneous CD20+ tumors were administered i.v. rituximab at 10 mg/kg or IGN002 at 5, 10 or 15 mg/kg. Serum and tumors were collected at 1, 4, 24 or 48 hours (hrs) to assess IGN002 stability and tumor uptake using sandwich ELISA. In the same model, we examined tumor growth inhibition (TGI) and survival in mice treated with rituximab up to 5 mg/kg or IGN002 at doses up to 6 mg/kg.

Results

IGN002 increased in serum in a dose-related manner with the peak levels achieved at 1-4 hrs (5mg/kg: 33±3; 10mg/kg: 155±5; 15mg/kg: 177±11 μg/ml) and a half-life of 24 hrs. At 48 hrs, IGN002 was still detectable in the circulation (5mg/kg: 25±2; 10mg/kg: 44±6; 15mg/kg: 45±3 μg/ml). Increases in IGN002 were also observed in the tumor at similar levels to rituximab. In the tumor, as hypothesized, IFNα2b increased in as dose-related manner with Cmax levels at 4 hrs of 41±12, 57±14 and 92±22 ng/mg of tumor tissue at 5, 10 and 15 mg/kg dose groups, respectively. At 48 hrs, IFNα2b levels were still detected (range: 18-38 ng/mg of tumor tissue). IGN002 improved survival at all doses investigated and increased inhibition of tumor growth when compared to rituximab with no adverse clinical signs.

Conclusions

IGN002 demonstrated adequate stability in the tumor resulting in the reduction in tumor mass and increased survival when compared to rituximab. Thus, demonstrating that the targeted delivery of IFNα2b to CD20+ tumor warrants further investigation in NHL patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Spectrum Pharmaceuticals.

Funding

Spectrum Pharmaceuticals.

Disclosure

S. Lakshmikanthan, P.S. Kolli, M. Tugnait, F. Lebel, J.A. Barrett: Shareholder/Stockholder/Stock options, Full/Part-time employment: Spectrum Pharmaceuticals. All other authors have declared no conflicts of interest.

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