SON-1010 plus trabectedin completes first safety review in advanced leiomyosarcoma/liposarcoma

The combination of investigational interleukin-12-based immunotherapy recombinant agent SON-1010 and trabectedin produced positive results in patients with advanced leiomyosarcoma (LMS) or liposarcoma (LPS), according to first safety review data (NCT05352750) from the expanded cohort of the Phase 1 SB101 trial.

The Safety Review Committee noted that there were no unexpected toxicities in the first 7 patients treated with the maximum tolerated dose (MTD) of SON-1010, which was 1,200 ng/kg. After an average treatment time of approximately 2 months, 1 patient experienced disease progression, and the other 6 patients were still able to tolerate the combination therapy. Adverse reactions (AEs) associated with either drug were mild or moderate in severity.

In addition, results from the annual review, which included all patients dosed to date (n=30), showed that common adverse events of any grade reported by at least 15% of patients related to SON-1010 or its combinations included fatigue, fever, chills and myalgia. The only treatment-related adverse event that occurred in at least 2 patients receiving trabectedin was moderate fatigue. Once the combined cohort is fully enrolled, data on response benefit will be assessed according to RECIST 1.1 criteria.

High doseThe 4-month stable prevalence rate of patients in the SON-1010 monotherapy group (n=6) was 83%; 4 of the patients were still receiving study treatment at 6 months, and no new safety issues were reported. One patient achieved sustained partial response (PR). Across the entire monotherapy cohort (n=24), 54% of patients showed evidence of clinical benefit from monotherapy during SON-1010 dose escalation.

Doctors have been working hard to improve sarcoma outcomes and are pleased to continue supporting the expandedSB101 trial. has extensive experience with trabectedin and believes in the ability of SON-1010 to enhance its therapeutic efficacy, as SON-1010 has demonstrated clinical benefit in patients with advanced sarcomas, including PR, as a monotherapy in clinical trials. LPS and LMS are the most common types of sarcoma, and they are difficult-to-treat diseases. While the U.S. approval of trabectedin has helped, there is room for improvement in all types of soft tissue sarcomas, and the drug appears to be applicable in recurrent ovarian cancer as well. At this stage, the safety profile of SON-1010 in combination with trabectedin is encouraging, and we look forward to conducting further clinical trials with a larger patient population.

It is worth noting that,In October 2015, the U.S. Food and Drug Administration approved trabectedin for the treatment of patients with unresectable or metastatic LPS or LMS who have previously received anthracycline-containing therapy. 2 This regulatory decision is supported by results from the Phase 3 study of ET743-SAR-3007 (NCT01343277). The drug is the first chemotherapy drug approved by the U.S. Food and Drug Administration to treat patients with advanced soft tissue sarcoma whose disease has progressed to primary treatment.

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 according to RECIST 1.1 criteria; receive standard of care therapy with no standard alternative treatment options; have an ECOG performance status of 0 or 1; weigh more than 50 kg to 120 kg; and have adequate organ and bone marrow function.

In the expansion cohort, patients receivedSON-1010 in combination with standard trabectedin for 21 days, using alternating dosing. The primary endpoints were safety and tolerability, as well as determination of the MTD and recommended Phase 2 dose. 3 secondary endpoints include objective response rate according to RECIST 1.1 criteria, as well as assessment of 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 participate in the open-label, single-arm expansion cohort. The expansion cohort, which aims to evaluate the combination therapy in patients with early-stage soft tissue sarcoma, provides an exciting opportunity to evaluate the potential of SON-1010 to turn ‘cold’ tumors into ‘hot’ and improve response to trabectedin in licensed chemotherapy indications.

Reference materials:https://www.onclive.com/view/son-1010-plus-trabectedin-completes-first-safety-review-in-advanced-leiomyosarcoma-liposarcoma