On March 26, 2025, Sonnet BioTherapeutics Holdings, Inc. (the "Company") reported the positive findings from the first safety review of the expansion cohort in its Phase 1 SB101 clinical trial evaluating SON-1010, the Company’s proprietary version of recombinant human interleukin-12 ("rhIL-12") configured using genetic fusion to the Company’s Fully Human Albumin Binding ("FHAB") platform, in combination with trabectedin ("Yondelis") in adult patients with advanced leiomyosarcoma ("LMS") or liposarcoma ("LPS") (Press release, Sonnet BioTherapeutics, MAR 26, 2025, View Source [SID1234651472]).The expansion cohort builds on the successful completion of monotherapy dose escalation and assignment of the SON-1010 maximum tolerated ("MTD") dose of 1200 ng/kg.
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The SB101 Safety Review Committee ("SRC") met to evaluate the initial status of the patients in the expansion cohort, all of whom are receiving the SON-1010/trabectedin combination, as enrollment continues. After an average treatment of slightly over two months, one patient progressed and the other six are tolerating treatment. Adverse events ("AEs") considered to be related to either drug have all been mild or moderate, suggesting that the two drugs do not appear to be adversely impacting each other. The annual review including all 30 patients dosed to date showed that common AEs considered related to SON-1010 monotherapy or in combination included fatigue, fever, chills, and myalgia in 15% or more; moderate fatigue was the only related AE in 2 or more of the patients treated with trabectedin to date. Full enrollment of the combination cohort will provide an opportunity to evaluate statistical evidence of benefit in the response using the standard RECIST paradigm, which may also confirm synergy. Meanwhile, five of the six patients in the SON-1010 high-dose monotherapy group (83%) showed stable disease at 4 months and four continue on trial at 6 months with no new safety concerns. The partial response ("PR") in one of those patients persists, confirming the potential for benefit of SON-1010 monotherapy at the MTD in this small cohort. Overall, 13 of the 24 patients studied during SON-1010 dose escalation (54%) had evidence of monotherapy clinical benefit.
The primary outcome measures for the Phase 1 SB101 trial are the safety, tolerability, pharmacokinetics ("PK") and pharmacodynamics ("PD") of SON-1010 and to establish the MTD. The Company has treated 7 patients over 2 months on average and expects to enroll up to 18 patients with unresectable, metastatic LMS or LPS in this open-label, single-arm expansion cohort. Patients are being treated with SON-1010 in combination with the standard 21-day trabectedin cycles, alternating the dosing of the two drugs. Trabectedin, the first approved chemotherapeutic drug for advanced soft-tissue sarcomas ("STS") after failure of primary therapy, works by preventing tumor cells from proliferating but has also been shown to have pro-inflammatory immune effects in the tumor microenvironment ("TME") that may be enhanced by the IL-12 activity in SON-1010. Trabectedin is approved in 76 countries globally for the treatment of advanced STS as a single-agent, and in 69 countries for relapsed ovarian cancer in combination with doxorubicin HCl liposome injection.