Sonnet BioTherapeutics has announced a significant expansion of its Phase 1 SB101 clinical trial, introducing a new combination therapy approach for soft tissue sarcoma patients. The study will evaluate the company's novel immunotherapeutic SON-1010 in combination with trabectedin, targeting patients with unresectable, metastatic liposarcoma or leiomyosarcoma.
Trial Design and Patient Population
The open-label, single-arm expansion cohort will enroll up to 18 patients who will receive SON-1010 alongside standard 21-day trabectedin cycles. The study has established a maximum tolerated dose (MTD) of 1200 ng/kg for SON-1010, with primary outcome measures focusing on safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD).
Dr. Richard Kenney, Sonnet's Chief Medical Officer, emphasized the strategic importance of treating earlier-stage patients: "The ability to assess earlier-stage patients is an exciting opportunity to evaluate the potential for SON-1010 to turn 'cold' tumors 'hot.' Most Phase 1 studies in oncology are done in patients with advanced disease, whose immune systems may not respond optimally after multiple types of chemotherapy."
Innovative Technology Platform
SON-1010 represents a breakthrough in IL-12 delivery, utilizing Sonnet's Fully Human Albumin Binding (FHAB®) platform. This proprietary technology extends the half-life and bioactivity of IL-12 through binding to native albumin in the serum. The mechanism specifically targets the tumor microenvironment (TME) through interactions with gp60 and Secreted Protein Acidic and Rich in Cysteine (SPARC).
Therapeutic Mechanism and Potential
The combination therapy leverages trabectedin's established role as a second-line treatment and its ability to activate tumor macrophages into a pro-inflammatory state. SON-1010 is expected to complement this activity by stimulating Natural Killer (NK) and T cells in the TME to increase interferon-gamma (IFNγ) production, potentially enhancing anti-tumor responses.
Dr. Pankaj Mohan, Sonnet's Founder and CEO, noted: "The Sonnet team has been studying the efficacy and safety of SON-1010 as a single agent, which has thus far suggested clinical benefit when administered as a monotherapy in patients with advanced solid tumors. We believe this synergy could improve the response in a serious type of cancer at an earlier stage of disease."
Broader Development Program
Beyond the sarcoma trial, SON-1010 is being evaluated in a Phase 1b/2a study (SB221) in combination with atezolizumab for platinum-resistant ovarian cancer, conducted in collaboration with Genentech. Safety updates from this trial are expected in Q1 2025.
The expansion of the SB101 trial marks a crucial step in Sonnet's development strategy, potentially positioning SON-1010 for a larger Phase 2 study that could establish the combination therapy as a new standard in soft tissue sarcoma treatment.
