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Poster discussion session - Immunotherapy of cancer 1

1598 - Intratumoral BO-112, a double-stranded RNA (dsRNA), alone and in combination with systemic anti-PD-1 in solid tumors

Date

20 Oct 2018

Session

Poster discussion session - Immunotherapy of cancer 1

Topics

Clinical Research;  Immunotherapy

Tumour Site

Presenters

Ivan Marquez Rodas

Authors

I. Marquez Rodas1, F. Longo2, M. Rodriguez-Ruiz3, A. Calles1, J.L. Pérez-Gracia4, A. Gomez-Rueda2, S. Lopez-Tarruella5, M. Ponz-Sarvisé4, R.M. Alvarez6, A. Soria2, E. de-Miguel7, J. Gayarre1, M..A. Aznar8, A. Calvo1, P.P. Lopez-Casas9, D. Tersago9, M. Quintero9, S. Martin-Algarra4, M. Martín10, I. Melero11

Author affiliations

  • 1 Medical Oncology, Hospital General Universitario Gregorio Marañon, 28009 - Madrid/ES
  • 2 Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 3 Radiation oncology, Clinica Universidad de Navarra, 31008 - Pamplona/ES
  • 4 Department Of Oncology, Clinica Universidad de Navarra, 31008 - Pamplona/ES
  • 5 Instituto De Investigación Sanitaria Gregorio Marañón, Ciberonc, Geicam, Universidad Complutense, - - Madrid/ES
  • 6 Department Of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid/ES
  • 7 Radiology, Hospital General Universitario Gregorio Marañon, 28009 - Madrid/ES
  • 8 Immunology And Immunotherapy, CIMA, 31008 - Pamplona/ES
  • 9 Bioncotech Therapeutics, Bioncotech Therapeutics, 46980 - Valencia/ES
  • 10 Instituto De Investigación Sanitaria Gregorio Marañón, Ciberonc, Geicam, Universidad Complutense, Madrid/ES
  • 11 Laboratory Of Immunology, Clinica Universitaria de Navarra, 31008 - Pamplona/ES
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Resources

Abstract 1598

Background

BO-112 is a dsRNA (poly I:C) formulated with the cationic carrier polyethylenimine, which improves its intracellular delivery. Preclinically it acts by activating TLR3, RIG-1 and MDA-5, leading to an immunogenic cell death and increasing immune-checkpoint inhibition effects. Intratumoral (IT) BO-112 alone or combined with systemic anti PD-1 is being analyzed in this first in human clinical trial (NCT02828098)

Methods

28 patients (pts) with solid tumors and metastases >1 cm amenable to IT injection were divided in 4 cohorts (C). C1: single IT BO-112 dose of 0.6 mg (N=6); C2: 1mg IT BO-112 qw x 2-3 doses (N=7). C3: 0.6 mg IT BO-112 qw x 2-3 doses (N=3); C4: Pts with primary refractory tumors to anti PD-1 were treated with 1mg IT BO112 qw x 2 or 3 doses before continuing nivolumab or pembrolizumab combined with BO-112, until progression, limiting toxicity or up to 1y (N=12). Pre & post treatment biopsies from the injected lesion were analysed for necrosis, apoptosis, immune infiltrate and gene expression profiles. PK, cytokines and circulating immune cells were studied in pre and post BO-112 blood samples. In C4, response by RECIST 1.1 was assessed.

Results

Main G3-5 AEs, biological effects of C1-3 and safety from C4 are summarized in the table. No safety warnings were detected with the combination. BO-112 was not detected in blood. In C4 (combination cohort) disease control rate at 1st assessment (9-10 weeks) was 7/12 (58%) and objective response rate 2/12 (17%), one in melanoma and one in renal cancer.

COHORT

G3-5 AEs N (%)

G3-5 related AEs N (%)

Necrosis or apoptosis (% evaluable)

Increase (Δ) in immune gene expression (% evaluable)

Δ circulating immune cells (%)

BO-112 Monotherapy

6 (38)

2 (13)

10/13 (77)

6/13 (46)

14/16 (88)

Combination BO-112+anti PD-1

8 (67)

0 (0)

NA

Conclusions

IT BO-112 has demonstrated a manageable safety profile alone and combined with anti PD-1. Its mechanism of action comprises direct antitumor effect, innate and adaptive immune system activation. Combination with anti PD-1 is feasible in anti PD-1 refractory pts. Preliminary efficacy analysis suggests the potential to halt or reverse primary resistance to anti-PD1 treatment. This cohort is being expanded to include up to 30 pts.

Clinical trial identification

NCT02828098

Editorial Acknowledgement

None

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