Sonnet BioTherapeutics Holdings announced the expansion of its Phase 1b/2a clinical trial evaluating SON-1010 in combination with atezolizumab for platinum-resistant ovarian cancer (PROC), following encouraging efficacy signals that showed a 66% response rate at the current maximum dose.
The company reported that 2 of 3 patients (66%) treated at the E6 dose of 1200 ng/kg demonstrated significant tumor responses, including a second partial response recently confirmed by RECIST criteria. This response rate prompted the Safety Review Committee to recommend adding an E7 cohort testing a 25% higher maintenance dose of 1500 ng/kg.
Strong Safety Profile Enables Dose Escalation
The SB221 study has demonstrated acceptable safety signals and clinical benefit during dose escalation, with controlled induction of interferon (IFN). According to Dr. Richard Kenney, Sonnet's Chief Medical Officer, "We are very pleased with the progress of the SB221 study and look forward to investigating the effect of a higher dose of SON-1010, with the hope that it could maximize efficacy without inducing cytokine toxicity."
The expansion follows completion of enrollment in the E6 dose expansion group, which provided an opportunity to study the safety of the combination in a larger population. Given the strong safety profile observed at the top dose, investigators are now evaluating whether the higher E7 dose can maximize efficacy while maintaining the favorable safety profile.
Addressing Unmet Need in Difficult-to-Treat Cancer
Dr. Robert Wenham, Chair of GYN Oncology at Moffitt Cancer Center and lead investigator for the SB221 study, emphasized the clinical significance of these results. "PROC patients typically have low response rates to currently approved therapies," he noted. "While more data are needed from the expansion group, the two PRs at the E6 dose are very exciting and represent some of the best data to date in support of a pure combination immunotherapy approach."
The controlled induction of IFN is particularly important, as Wenham explained, because it is necessary for immunotherapeutic control of tumors while also inducing PD-L1 expression on tumor cells, which supports the rationale for combining SON-1010 with atezolizumab.
Novel IL-12 Platform Technology
SON-1010 utilizes Sonnet's proprietary FHAB (Fully Human Albumin-Binding) technology, which links unmodified single-chain human IL-12 with an albumin-binding domain. This approach is designed to deliver IL-12 to local tumor tissue, turning immunologically 'cold' tumors 'hot' by stimulating IFN and activating innate and adaptive immune cell responses.
The technology addresses historical safety concerns with IL-12, which led to severe adverse effects in initial Phase 2 studies in the late 1990s with daily dosing. By linking IL-12 to a fully human single chain variable fragment that binds albumin and extends half-life, the platform may allow higher, potentially more effective doses to be given safely.
Broader Clinical Development Program
The promising results build on data from Sonnet's SB101 monotherapy study, which showed a clinical benefit rate of 83% (5 of 6 patients) at the 1200 ng/kg dose in advanced solid tumors, including one patient with soft tissue sarcoma who achieved a partial response. That study is also being expanded to evaluate SON-1010 alternating with trabectedin in soft tissue sarcoma patients.
Timeline and Next Steps
Raghu Rao, Sonnet's Interim Chief Executive Officer, outlined the path forward: "We will follow the patients currently being treated at the E6 dose to assess longer-term safety and tumor responses, and look forward to studying a 25% higher dose in the E7 cohort before selecting the best dose and moving to Part 2."
Topline readouts from the combination study are expected in the fourth quarter of 2025. The randomized Phase 2a portion will evaluate patients with PROC at one of the two highest doses compared to standard of care. The company continues to seek partnership opportunities to support later-stage development of SON-1010.
The SB221 study is a global Phase 1b/2a multicenter, dose-escalation and randomized proof-of-concept study assessing safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SON-1010 administered subcutaneously, either alone or in combination with intravenously administered atezolizumab provided by Genentech, a member of the Roche Group.
