SON-1010 Plus Trabectedin Completes First Safety Review in Advanced Leiomyosarcoma/Liposarcoma

March 26, 2025

Findings from the safety review of SON-1010 plus trabectedin in patients with advanced leiomyosarcoma or liposarcoma were positive.

SON-1010 Plus Trabectedin in Advanced Leiomyosarcoma/Liposarcoma | Image Credit: © MdBabul– stock.adobe.com

The combination of the investigational interleukin-12–based immunotherapeutic recombinant agent SON-1010 plus trabectedin (Yondelis) generated positive findings in patients with advanced leiomyosarcoma (LMS) or liposarcoma (LPS), according to data from the first safety review of the expansion cohort of the phase 1 SB101 trial (NCT05352750).1

The Safety Review Committee noted no unexpected toxicities in the first 7 patients treated with the maximum tolerated dose (MTD) of SON-1010, which was 1200 ng/kg. Following a mean treatment duration of approximately 2 months, 1 patient experienced disease progression, and the other 6 patients were still tolerating treatment with the combination. Adverse effects (AEs) deemed related to either agent have been mild or moderate in severity.

Moreover, findings from the annual review, which included all patients dosed to date (n = 30), showed that common any-grade AEs related to SON-1010 or the combination that were reported in at least 15% of patients included fatigue, fever, chills, and myalgia. The only treatment-related AE occurring in at least 2 patients who received trabectedin was moderate fatigue. Data regarding response benefit via RECIST 1.1 criteria will be evaluated following full enrollment of the combination cohort.

Patients in the high-dose SON-1010 monotherapy group (n = 6) achieved a 4-month stable disease rate of 83%; 4 of these patients remained on study treatment at 6 months with no new safety concerns reported. One of these patients achieved an ongoing partial response (PR). In the overall monotherapy cohort (n = 24), 54% of patients displayed evidence of monotherapy clinical benefit during SON-1010 dose escalation.

“Our physicians are always working to improve the outcomes in sarcoma and [are] very pleased to continue to support the expanded SB101 trial,” Sant P. Chawla, MD, the director of the Sarcoma Oncology Center in Santa Monica, California, stated in a news release. “We have a wealth of experience with trabectedin and believe that SON-1010 has the ability to improve its therapeutic effectiveness, given that SON-1010 as a clinical trial monotherapy has already demonstrated clinical benefit in [patients with] advanced sarcoma, including a PR. LPS and LMS are the most common types of sarcoma, which are difficult diseases to treat. While the approval of trabectedin in the United States has helped, there is room for improvement in all types of soft tissue sarcomas, and the drug appears to have utility in the relapsed ovarian cancer setting as well. The safety of SON-1010 in combination with trabectedin is encouraging at this stage, and we look forward to the results from the larger group of patients for further clinical trials.”

Notably, in October 2015, the FDA approved trabectedin for the treatment of patients with unresectable or metastatic LPS or LMS who had received a prior anthracycline-containing regimen.2 The regulatory decision was supported by findings from the phase 3 ET743-SAR-3007 study (NCT01343277). The agent was the first FDA-approved chemotherapy for the treatment of patients with advanced soft tissue sarcomas following disease progression with primary therapy.1

The first-in-human study of SON-1010 enrolled adult patients with advanced or metastatic solid epithelial or mesenchymal tumors.3 Eligible patients needed to have measurable disease per RECIST 1.1 criteria; have received standard-of-care therapies and have no standard alternative treatment options; have an ECOG performance status of 0 or 1; have a body weight of over 50 kg up to 120 kg; and have adequate organ and bone marrow function.

In the expansion cohort, patients are receiving SON-1010 in combination with standard 21-day trabectedin cycles using alternating dosing.1 The primary end points are safety and tolerability, as well as establishing the MTD and the recommended phase 2 dose.3 Secondary end points include objective response rate per RECIST 1.1 criteria, as well as evaluating serum and urine concentrations of SON-1010, the effect of SON-1010 on serum cytokine levels, and SON-1010 immunogenicity.

Up to 18 patients with unresectable or metastatic LMS or LPS are expected to enroll in the open-label, single-arm expansion cohort.1

“The goal for the expansion cohort is to assess combination therapy in earlier-stage patients with soft tissue sarcomas, which provides an exciting opportunity to evaluate the potential for SON-1010 to turn ‘cold’ tumors ‘hot’ and improve the response of trabectedin in a licensed chemotherapy indication,” Pankaj Mohan, PhD, chief executive officer and founder of Sonnet BioTherapeutics, added in the news release.1 “We believe the results of this expansion cohort will position SON-1010 for a larger phase 2 study that could establish the combination of SON-1010 and trabectedin as a new and potentially improved treatment for soft tissue sarcoma at an earlier stage. Furthermore, the global market opportunity for trabectedin is $2.1 billion, and sarcoma still represents an unmet medical need, which we believe opens up another potential opportunity for partnering.”

References

Sonnet BioTherapeutics successfully completes first safety review of SON-1010 in combination with trabectedin in certain sarcomas. News release. Sonnet BioTherapeutics. March 26, 2025. Accessed March 26, 2025. https://www.sonnetbio.com/news-media/press-releases/detail/121/sonnet-biotherapeutics-successfully-completes-first-safety
U.S. FDA approves Yondelis (trabectedin) for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma, two common subtypes of soft tissue sarcoma. News release. Johnson&Johnson. October 23, 2015. Accessed March 26, 2025. https://www.jnj.com/media-center/press-releases/us-fda-approves-yondelis-trabectedin-for-the-treatment-of-patients-with-unresectable-or-metastatic-liposarcoma-or-leiomyosarcoma-two-common-subtypes-of-soft-tissue-sarcoma
Phase 1 study of SON-1010 in adult patients with advanced solid tumors. ClinicalTrials.gov. Updated April 12, 2024. Accessed March 26, 2025. https://clinicaltrials.gov/study/NCT05352750