8-K: Sonnet BioTherapeutics Expands Phase 1 Trial of SON-1010 with Trabectedin for Sarcomas

Sonnet BioTherapeutics is expanding its Phase 1 SB101 trial to evaluate the combination of SON-1010 with trabectedin in certain sarcomas, following positive monotherapy data.

Summary

• Sonnet BioTherapeutics is expanding its Phase 1 SB101 clinical trial to include a cohort evaluating SON-1010 in combination with trabectedin for advanced soft-tissue sarcomas (STS).
• The expansion follows successful completion of monotherapy dose escalation for SON-1010.
• The trial will explore the immune-oncology impact of SON-1010 at the maximum tolerated dose (MTD) of 1200 ng/kg in combination with trabectedin.
• Up to 18 patients with unresectable, metastatic liposarcoma or leiomyosarcoma will be enrolled in this open-label, single-arm cohort.
• Patients will receive SON-1010 in combination with standard 21-day trabectedin cycles, alternating the dosing of the two drugs.
• The primary outcome measures are safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SON-1010.
• Topline safety data for the combination is expected in the second half of calendar year 2025.
• The company believes this combination could lead to a larger Phase 2 study and a new treatment for STS.
• SON-1010 is a proprietary version of recombinant human interleukin-12 (rhIL-12) using the company's Fully Human Albumin Binding (FHAB) platform.
• The FHAB platform extends the half-life and bioactivity of IL-12 by binding to native albumin in the serum.
• Trabectedin is an approved chemotherapeutic drug for certain advanced soft-tissue sarcomas and is known to activate tumor macrophages.
• The company believes SON-1010 can complement trabectedin by activating NK and T cells in the tumor microenvironment (TME).

Sentiment

Score: 8

Explanation: The document conveys a positive outlook due to the expansion of the clinical trial and the potential for a new treatment option. The company is moving forward with its clinical program and has a clear strategy. However, it is still early in the clinical development process.

Positives

• The expansion of the Phase 1 trial suggests positive initial results from the monotherapy use of SON-1010.
• The combination of SON-1010 and trabectedin has the potential to improve the therapeutic window for soft-tissue sarcoma patients.
• The trial targets an unmet need in the treatment of soft-tissue sarcomas.
• The FHAB platform enhances the delivery and effectiveness of SON-1010.
• The combination has the potential to enhance progression-free survival (PFS) in some patients.
• The study could position SON-1010 for a larger Phase 2 study.
• The company is collaborating with Genentech on another trial for SON-1010 in combination with atezolizumab for ovarian cancer.

Negatives

• The trial is still in Phase 1, so the efficacy of the combination is not yet proven.
• The trial is limited to a small number of patients (up to 18).
• The trial is open-label, which may introduce bias.
• The company is relying on forward-looking statements, which are subject to risks and uncertainties.

Risks

• The clinical trial may not demonstrate the expected safety or efficacy of the combination therapy.
• The company may face challenges in enrolling the required number of patients.
• The development of SON-1010 and its combination with trabectedin is subject to regulatory approvals.
• The company's financial performance is subject to risks and uncertainties.
• There is no guarantee that the combination will be successful in a larger Phase 2 study.

Future Outlook

The company anticipates that the results of this expansion cohort could position SON-1010 for a larger Phase 2 study, potentially establishing the combination of SON-1010 and trabectedin as a new treatment for STS. The company also expects an update on safety at the MTD in the Phase 1b/2a study of SON-1010 with atezolizumab for ovarian cancer in Q1 2025.

Management Comments

• Dr. Sant Chawla, Principal Investigator at the Sarcoma Oncology Center, stated that they were excited to see the approval of trabectedin and believe there is a large unmet need for the treatment of STS.
• Richard Kenney, M.D., Sonnet's Chief Medical Officer, mentioned the opportunity to evaluate the potential for SON-1010 to turn cold tumors hot.
• Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer, stated that the company has seen clinical benefit when SON-1010 is administered as a monotherapy and believes the combination could improve the response in a serious type of cancer.

Industry Context

This announcement is relevant to the broader oncology field, particularly in the development of immunotherapies and combination therapies for solid tumors. The focus on soft-tissue sarcomas, a challenging cancer type, highlights the need for new treatment options. The combination of an immunotherapy (SON-1010) with a chemotherapy (trabectedin) reflects a growing trend in cancer treatment.

Comparison to Industry Standards

• The use of a maximum tolerated dose (MTD) of 1200 ng/kg for SON-1010 is consistent with standard Phase 1 trial designs in oncology.
• The trial design, using a 3+3 oncology design, is a common approach for dose escalation studies.
• The combination of an immunotherapy with a chemotherapy is a common strategy in oncology drug development, with examples such as Keytruda with chemotherapy in lung cancer.
• The focus on soft-tissue sarcomas is relevant as this is a difficult to treat cancer with limited treatment options, similar to other rare cancers where new therapies are needed.
• The use of a FHAB platform to enhance the delivery of IL-12 is a novel approach, with other companies using different methods to improve the delivery of immunotherapies.

Stakeholder Impact

• Shareholders may view this as positive news, potentially increasing the value of the company.
• Patients with soft-tissue sarcomas may benefit from a new treatment option.
• Employees may be motivated by the progress of the clinical trial.
• The company's partners, such as Genentech, may be encouraged by the progress.

Next Steps

• Enrollment of up to 18 patients in the new cohort of the Phase 1 SB101 trial.
• Completion of enrollment in the first half of calendar year 2025.
• Collection of topline safety data for the combination of SON-1010 with trabectedin, expected in the second half of calendar year 2025.
• Potential progression to a larger Phase 2 study if the results are positive.
• Continued enrollment in the Phase 1b/2a study of SON-1010 with atezolizumab for ovarian cancer.
• Update on safety at the MTD in the Phase 1b/2a study of SON-1010 with atezolizumab for ovarian cancer expected in Q1 2025.

Key Dates

Keywords

SON-1010, Trabectedin, Sarcoma, Immunotherapy, Clinical Trial, Phase 1, FHAB, IL-12, Soft-tissue sarcoma, Oncology