Data Compilation Highlights Potential of SON-1010 to Enhance Therapeutic Efficacy in Solid Tumors

SON-1010 (IL-12-FHAB), an IL-12–based immunotherapy, is being investigated for its potential to improve treatment efficacy in patients with solid tumors, either as a monotherapy or in combination with other agents. Compiled data presented at the 2025 AACR IO Annual Meeting showed the potential for SON-1010 to improve the pharmacokinetic (PK) profile of standard therapies, decrease toxicity risk, and provide a broader therapeutic index.1,2

SON-1010 is a novel recombinant human version of IL-12 that employs Fully Human Albumin Binding (FHAB) technology, which links unmodified single-chain IL-12 to the albumin-binding domain of the single-chain antibody fragment A10m3, enabling albumin binding at both physiologic and acidic pH.1 This targeted approach could enhance drug accumulation in tumors, providing dose-sparing benefits and potentially improving efficacy.

This mechanism is particularly relevant for non–small cell lung cancer (NSCLC), melanoma, head and neck cancer, sarcoma, and certain gynecological malignancies, where proteins such as Secreted Protein and Rich in Cysteine (SPARC) and glycoprotein 60 (GP60) facilitate tumor targeting.

“Recombinant interleukins have generally had limited clinical success due to inefficient tumor targeting, short half-lives, and off-target toxicity. As previously disclosed, our novel FHAB platform has demonstrated the potential for us to design product candidates that safely extend the half-life of cytokines and deliver them to the tumor, where they can convert the immunological response from ‘cold’ to ‘hot’ and potentially realize the promise of immunotherapy,” Pankaj Mohan, PhD, founder and chief executive officer of Sonnet explained in a news release.

Currently, several monotherapy and combination approaches are being explored in clinical studies to evaluate the potential role for SON-1010 in various solid tumors.

The phase 1b/2a SB221 trial (NCT05756907) is assessing co-administration of SON-1010 with atezolizumab (Tecentriq) in patients with advanced solid tumors with a particular focus on those with platinum-resistant ovarian cancer.2 Findings from SB221 demonstrated that SON-1010 in combination with atezolizumab was well tolerated in patients with platinum-resistant ovarian cancer with no dose-limiting toxicities (DLTs) or serious adverse effects (AEs) observed among evaluable patients (n = 14).

Results from this study also indicated that half of patients achieved stable disease at their first follow-up CT scan, including 4 patients showing signs of disease progression at study entry; the stable disease rate at 4 months was 31% (n = 4/13). The most common any-grade treatment-related AEs (TRAEs) reported in evaluable patients (n = 16) included fatigue (56%), pyrexia (31%), myalgia (12%), dizziness (12%), chills (12%), nausea (25%), vomiting (19%), diarrhea (12%), anorexia (19%), and pneumonitis (19%). The study continues to evaluate the recommended phase 2 dose (RP2D). In part 2 of the study, patients with platinum-resistant ovarian cancer will be randomly assigned to receive SON-1010 at the RP2D plus atezolizumab; or standard-of-care therapy comprising paclitaxel, pegylated liposomal doxorubicin, or topotecan.

Additionally, the phase 1 SB101 trial (NCT05408572) is evaluating SON-1010 as monotherapy in patients with advanced solid tumors, as well as in alternating administration with trabectedin (Yondelis) in patients with sarcoma. The goal of the alternate dosing is to promote a pro-inflammatory phenotype in the tumor microenvironment, potentially sensitizing tumors to immunotherapy. Findings from the trial showed that SON-1010 in combination with trabectedin was well tolerated in patients with unresectable or metastatic liposarcoma or leiomyosarcoma who had previously received doxorubicin. Notably, during the study, the starting dose of trabectedin was reduced from 1.5 mg/m² to 1.2 mg/m² to mitigate potential overlapping toxicities.

Additionally, the first 5 patients with sarcoma treated with the combination experienced no unexpected toxicities. The study continues to evaluate higher maintenance doses of SON-1010 to optimize immune activation and therapeutic benefit in these patients.

“We are pleased to share the compilation of data in this poster presentation and look forward to announcing additional data from our ongoing studies evaluating our SON-1010 platform in 2025,” Mohan concluded in the news release.1

Notably, the planned phase 1/2a SOC-241 trial is seeking to evaluate SON-1210 (IL12-FHAB-IL15)—a second product candidate from Sonnet BioTherapeutics.1,2 After being evaluated as monotherapy during dose escalation, SON-1210 will be given in alternation with NALIRIFOX (irinotecan liposome [Onivyde] oxaliplatin, 5-fluorouracil, and leucovorin) in the frontline treatment of patients with advanced pancreatic ductal adenocarcinoma with the goal of enhancing response rates and disease control.2

References

1. Sonnet BioTherapeutics presents compilation of data highlighting the potential of SON-1010 as a monotherapy or a combination therapy to improve the treatment of solid tumors. Sonnet BioTherapeutics. February 26, 2025. Accessed March 3, 2025. https://www.sonnetbio.com/news-media/press-releases/detail/118/sonnet-biotherapeutics-presents-compilation-of-data
2. Chawla SP, Chua VS, Chawla NS, et al. Combination immunotherapy with an albumin-binding interleukin-12 fusion protein that extends cytokine half-life, targets the tumor microenvironment, and enhances therapeutic efficacy. Presented at: 2025 AACR IO; February 23-26, 2025; Los Angeles, CA. Abstract LB-B005.