Sonnet says SON-1010 demonstrates ‘strong safety profile’ in atezolizumab combo

Sonnet BioTherapeutics (SONN) announced safety results of SON-1010 at the highest dose combined with atezolizumab in the Phase 1b/2a clinical trial in adult patients with advanced solid tumors or platinum-resistant ovarian cancer. Based on positive feedback from a formal evaluation by the Safety Review Committee for the SB221 study, the study can now advance to the expansion phase, which will study the preliminary effect of the combination at the MTD, before proceeding to a Phase 2a randomized comparison with the standard of care in patients with PROC. The SB221 study was designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of increasing doses of SON-1010 administered with atezolizumab. The primary goal for the first part of the study was to establish the MTD in combination with the immune checkpoint inhibitor. A total of 19 subjects were treated during dose escalation and one patient with PROC had a partial response at the highest dose. The SB221 SRC review at the completion of dose expansion in combination with atezolizumab concluded that fatigue, fevers, and gastrointestinal symptoms were the most common adverse effects; no dose-limiting toxicity or cytokine release syndrome were seen. The only related serious adverse event during dose escalation was Grade 2 pneumonitis, which is a known adverse event with atezolizumab. One patient with PROC had a 44% tumor size reduction, indicating a partial response, along with a more than 2-fold reduction in the CA 125 ovarian cancer biomarker. SON-1010 monotherapy in the SB101 study led to a PR at the same MTD in a patient with sarcoma. SON-1010 may work best with an ICI, particularly with immunologically ‘cold’ tumors that are high in secreted protein acidic and rich in cysteine, such as ovarian cancer. Binding to native albumin in the serum extends the half-life and bioactivity of the IL-12 component, which also allows targeting of and retention in the TME by strong binding to gp60 and SPARC. Safety has been a concern since the initial Phase 2 study of rhIL-12 in the late 1990’s, where daily dosing led to severe adverse effects. While safer dosing strategies have since been developed with rhIL-12, the promise of improved tumor control in humans has not been achieved using doses that are also demonstrated to be safe. Linking the IL-12 to a fully human single chain variable fragment that binds albumin and extends the half-life may finally allow higher doses that are potentially more effective to be given safely. The preclinical and mechanistic characterization of SON-1010, the Company’s proprietary version of recombinant human interleukin-12 configured using genetic fusion to Sonnet’s Fully Human Albumin Binding platform, was recently published. All enrolled patients have advanced solid tumors and all patients at the higher doses have PROC, including those enrolled in a final 1200 ng/kg dose-escalation cohort. The SB221 trial employed a ‘desensitizing’ first dose of 300 ng/kg to take advantage of the known tachyphylaxis with rhIL-12, with the intention of minimizing toxicity while allowing for higher maintenance doses. The safety and toxicity profile that has developed is typical for a Phase 1 oncology trial, with the majority of adverse events being reported as mild and transient and there has been no evidence of cytokine release syndrome. Of the 19 patients dosed to date, 8 of the 15 evaluable patients had SD at the first follow-up CT scan and 5 of the 15 evaluable patients remained stable at four months, suggesting SON-1010 is showing clinical benefit. While the follow-up is still early, four of those 15 patients were still on trial at 6 months, including 3 with SD and one with an unconfirmed PD. As noted, one of the PROC patients in the highest SON-1010 dose cohort had a PR at 2 months.