SON-1010 (IL12-FHAB) synergizes with trabectedin in advanced soft-tissue sarcoma
Presenter: Richard Kenney, MD Session: Phase I Clinical Trials Time: 4/21/2026 9:00:00 AM → 4/21/2026 12:00:00 PM
Authors
Sant Chawla 1 , Victoria Chua 1 , Neal Chawla 1 , Erlinda M. Gordon 1 , John Cini 2 , Richard Kenney 3 1 Sarcoma Oncology Center, Santa Monica, CA, 2 Sonnet Biotherapeutics Inc, Princeton, NJ, 3 Sonnet Biotherapeutics Inc, Princeton, CA
Abstract
Introduction: IL-12 is a potent multifunctional regulator of cell-mediated immunity that activates NK, NKT, Th1, and CTL cells to produce IFNγ and efficiently kill tumor cells in mice, yet clinical studies of rhIL-12 at the MTD of 500 ng/kg have failed to show adequate benefit. Single-chain native IL‑12 linked to a fully-human albumin binding (F H AB ® ) scFv domain (SON-1010) provides enhanced targeting and retention of the cytokine in the tumor microenvironment (TME) through albumin binding to locally over-expressed FcRn, GP60, and SPARC, with an improved PK profile and broader therapeutic index. SON-1010 was given as monotherapy in the dose-escalation portion of study SB101 in advanced solid tumors and 1 patient had a PR at the maximum dose of 1200 ng/kg. In the second part of this study, SON-1010 was used with trabectedin (Yondelis ® ) in metastatic soft-tissue sarcoma (STS). Trabectedin, a DNA-binding chemotherapy, is approved as 2nd line in unresectable or metastatic STS and is associated with a median PFS of 4.2 months. It also activates macrophages toward a pro-inflammatory phenotype in the TME. Methods: SB101 is a first-in-human Phase 1 study that initially assessed the safety, PK, PD, and efficacy of SON-1010 dosed SC every 3 weeks using a 3+3 design (NCT05352750). A relatively low desensitizing 1 st dose of SON-1010 activates the tachyphylaxis associated with IL-12, followed by higher maintenance doses in each cohort. Safety was reviewed in each group before dose escalation. An expansion cohort was enrolled that alternated trabectedin with SON-1010 at 1200 ng/kg in 3 week cycles. This cohort was designed to establish benefit using a Simon 2-stage approach with α of 0.1 and 80% power in 18 patients with STS. The first stage required at least one of the first 7 patients to show clinical benefit, defined as a RECIST response or stable disease (SD) at 4 months. The second stage required at least 4 patients to show the same. Results: All adverse events (AEs) have been transient and dosing was well tolerated; most have been mild or moderate. There were no dose-limiting toxicities and no patients were discontinued due to related AEs. The most common AEs considered related to SON-1010 were fatigue, fever, chills, and myalgia. Fourteen of the 18 patients (78%) in the combination cohort had clinical benefit at 4 months, including 1 confirmed PR. Eight patients have progressed to date and one stopped due to surgery. Nine patients remain on study, so the median PFS has not yet been reached; the mean PFS is currently 6.9 months. Conclusion: SON-1010, an extended half-life version of rhIL-12 that targets the TME, acts safely and synergistically with trabectedin to augment the potential for tumor control in STS, addressing a significant unmet medical need. The responses achieved with monotherapy or in combination could increase with higher doses. SON-1010 may act by immunologically ‘warming’ the TME to improve the effectiveness of trabectedin in extending the PFS.
Disclosure
S. Chawla, Sonnet Biotherapeutics Inc Stock, ), Travel. V. Chua, None.. N. Chawla, None.. E. M. Gordon, None. J. Cini, Sonnet Biotherapeutics Inc Employment, Stock Option. R. Kenney, Sonnet Biotherapeutics Inc g., Board of Directors, non-salaried role), Independent Contractor, Stock, Stock Option, Other Securities, Travel, Patent.
Cited in
Control: 10536 · Presentation Id: 12085 · Meeting 21436