SON-1010 Plus Atezolizumab Is Safe, Displays Preliminary Efficacy in Platinum-Resistant Ovarian Cancer

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Treatment with the combination of the immunotherapeutic recombinant drug SON-1010 (IL12-FHAB) and atezolizumab (Tecentriq) was safe and generated signs of clinical activity in patients with platinum-resistant ovarian cancer and other advanced solid tumors, according to topline data from the phase 1/2 SB221 trial (NCT05756907).1

Findings demonstrated that among evaluable patients from the dose-escalation portion of the study (n = 19), no dose-limiting toxicities were recorded, and no instances of cytokine release syndrome occurred. One patient experienced a treatment-related serious adverse effect was grade 2 pneumonitis, which has previously been associated with atezolizumab.

Regarding efficacy, 1 patient with platinum-resistant ovarian cancer experienced a partial response with a 44% reduction in tumor size and 2-fold reduction in CA 125 levels. In all evaluable patients with advanced solid tumors (n = 15), 53% experienced stable disease at their first follow-up CT scan, and 33% of patients remained in stable disease at 4 months. At data cutoff, 4 patients remained on the study at 6 months; 3 patients had stable disease and 1 had unconfirmed progressive disease.

After reviewing topline safety data, the study’s safety review committee granted permission for the study to proceed to dose expansion, where SON-1010 will be further evaluated at the (MTD) tolerated dose established during dose escalation. Then in phase 2a, patients with platinum-resistant ovarian cancer will be randomly assigned to receive the combination vs standard-of-care therapy.

“[Patients with] platinum-resistant ovarian cancer remain a very difficult group to treat, and these patients continue to have low response rates to currently approved therapies,” Robert Wenham, MD, chair of the Department of GYN Oncology at Moffitt Cancer Center and the principal investigator of the SB221 trial, stated in a news release. “It has been difficult to show efficacy using existing immune drugs like checkpoint inhibitors. This patient’s tumor reduction using an immune checkpoint inhibitor in combination with a novel extended PK IL-12 immune therapeutic is exciting. We are looking forward to entering the next stage of the SB221 trial.”

SON-1010 features an unmodified single-chain human IL-12 that is linked with the albumin-binding domain of A10m3, a single-chain antibody fragment. The fragment was selected to bind albumin at normal pH and acidic pH typically found in the tumor microenvironment.

SB221 is an open-label study enrolling patients at least 18 years of age with histologically or cytologically locally advanced or metastatic solid tumors (part 1) and patients with platinum-resistant ovarian cancer (part 2).2 All patients are required to have an ECOG performance status of 0 or 1; and adequate organ and bone marrow function.

Investigators are excluding patients who were hospitalized fur to subacute bowl obstruction, other complications from cancer, or any major surgery within 28 days of the first day of cycle 1 of treatment. Other key exclusion criteria consist of active liver disease from any cause; administration of a live or live-attenuated vaccine within 30 days of first study treatment; and active central nervous system metastases and/or carcinomatous meningitis.

During part 1 of the study, SON-1010 is being evaluated at 1 of 5 dose levels in combination with atezolizumab. During dose expansion, the recommended phase 2 dose of SON-1010 will be further evaluated alone and in combination with atezolizumab in patients with platinum-resistant ovarian cancer. During phase 2, patients with platinum-resistant ovarian cancer will be randomly assigned to received SON-1010 plus atezolizumab or SOC therapy.

Safety and the establishment of the RP2D are serving as the trial’s primary end points. Antitumor activity is a secondary end point, including progression-free survival.

“This topline safety data release from our atezolizumab combination program is another significant milestone for Sonnet’s clinical development,” Raghu Rao, interim chief executive officer of Sonnet BioTherapeutics, stated in a news release.1 “Safety of [SON-1010] has been within expected levels, and the comparison with dosing in healthy volunteers provided strong evidence of tumor targeting and accumulation in humans. We have used this trial to establish the MTD of combination with an immune checkpoint inhibitor and will continue to follow the patients currently being treated to assess longer-term safety and tumor responses. Sonnet continues to seek partnership opportunities to help support later-stage development of SON-1010.”

References

1. Sonnet’s SON-1010 demonstrates a strong safety profile in combination with atezolizumab for treatment of platinum-resistant ovarian cancer, including a partial response at the highest dose. News release. Sonnet BioTherapeutics. April 4, 2025. Accessed April 8, 2025. https://www.sonnetbio.com/news-media/press-releases/detail/124/sonnets-son-1010-demonstrates-a-strong-safety-profile-in
2. Combination of SON-1010 (IL12-FHAB) and atezolizumab in patients with platinum-resistant ovarian cancer. ClinicalTrials.gov. Updated October 23, 2023. Accessed April 8, 2025. https://clinicaltrials.gov/study/NCT05756907