Checkpoint inhibitors provide viable treatment alternatives to chemotherapy and/or radiation for patients with solid tumors, but there remains a robust need for more effective combination treatment regimens. With the objective of improving the checkpoint inhibitor response rate, Sonnet BioTherapeutics is developing a targeted approach using the company’s Fully Human Albumin binding (FHAB™) platform. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only Interleukin 12 (IL-12), but a variety of synergistic and potent immunomodulators. SON-1010 is currently undergoing Phase 1 clinical study in cancer patients and this preclinical study was designed to explore the combination potential with a checkpoint inhibitor (anti-PD1).
“We are excited to see that the combination of SON-1010 with an anti-PD1 antibody yielded compelling data in this preclinical model” said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer, and further added that, “These data support our strategy of pairing SON-1010 with a checkpoint inhibitor, with the goal of developing an improved treatment option for cancer patients.”
Experimental Study Design: Three randomized cohorts of nine mice (n = 27), each with 150 mm3 B16F10 melanoma tumors, were dosed with 3µg IL12-FHAB and/or 10µg anti-PD1 antibody on days 0, 4 and 8 while the placebo cohort was not treated. Mean tumor volumes were measured every two or three days through an 18-day period.
Table 1: Mean Comparisons of Tumor Volume Growth Inhibition
|Test Article||Mean Tumor|
Volume (mm3) – Day 14
|Tumor Growth Inhibition Ratios|
( % Inhibition )
|Placebo (n = 9)||2260||–|
|Anti-PD1 antibody (n = 9)||2016||10.7%|
|Anti-PD1 + IL12-FHAB (n = 9)||472||79.1%|
Compared to the tumor-bearing placebo group at day 14, the treatment groups administered three doses of anti-PD1 antibody or three doses of the IL12-FHAB + anti-PD1 antibody combination resulted in 10.7% and 79.1% tumor growth inhibition, respectively.