Sonnet’s SON-1010 Demonstrates a Strong Safety Profile in Combination with Atezolizumab for Treatment of Platinum-Resistant Ovarian Cancer, Including a Partial Response at the Highest Dose
Sonnet BioTherapeutics (NASDAQ:SONN) announced positive safety results for its SON-1010 drug in combination with atezolizumab for treating platinum-resistant ovarian cancer (PROC). The Phase 1b/2a clinical trial established a maximum tolerated dose (MTD) of 1200 ng/kg without dose-limiting toxicity or cytokine release syndrome.
Key findings include:
- 5 of 15 evaluable patients (33%) showed stable disease at four months post-treatment
- One PROC patient achieved partial response with 44% tumor size reduction
- Common side effects included fatigue, fevers, and gastrointestinal symptoms
- 8 of 15 evaluable patients (53%) showed stable disease at first follow-up
- 4 patients continued treatment beyond 6 months
The study will now advance to the expansion phase to evaluate the combination's preliminary effect at MTD before proceeding to Phase 2a randomized comparison with standard care in PROC patients.
Sonnet BioTherapeutics (NASDAQ:SONN) ha annunciato risultati positivi di sicurezza per il suo farmaco SON-1010 in combinazione con atezolizumab per il trattamento del cancro ovarico resistente al platino (PROC). Lo studio clinico di Fase 1b/2a ha stabilito una dose massima tollerata (MTD) di 1200 ng/kg senza tossicità limitante della dose o sindrome da rilascio di citochine.
I risultati chiave includono:
- 5 dei 15 pazienti valutabili (33%) hanno mostrato malattia stabile a quattro mesi dal trattamento
- Un paziente con PROC ha raggiunto una risposta parziale con una riduzione del 44% della dimensione del tumore
- Gli effetti collaterali comuni includevano affaticamento, febbre e sintomi gastrointestinali
- 8 dei 15 pazienti valutabili (53%) hanno mostrato malattia stabile al primo follow-up
- 4 pazienti hanno continuato il trattamento oltre i 6 mesi
Lo studio passerà ora alla fase di espansione per valutare l'effetto preliminare della combinazione alla MTD prima di procedere a un confronto randomizzato di Fase 2a con le cure standard nei pazienti con PROC.
Sonnet BioTherapeutics (NASDAQ:SONN) anunció resultados positivos de seguridad para su medicamento SON-1010 en combinación con atezolizumab para el tratamiento del cáncer de ovario resistente al platino (PROC). El ensayo clínico de Fase 1b/2a estableció una dosis máxima tolerada (MTD) de 1200 ng/kg sin toxicidad limitante de la dosis ni síndrome de liberación de citoquinas.
Los hallazgos clave incluyen:
- 5 de 15 pacientes evaluables (33%) mostraron enfermedad estable a los cuatro meses después del tratamiento
- Un paciente con PROC logró una respuesta parcial con una reducción del tamaño del tumor del 44%
- Los efectos secundarios comunes incluyeron fatiga, fiebre y síntomas gastrointestinales
- 8 de 15 pacientes evaluables (53%) mostraron enfermedad estable en el primer seguimiento
- 4 pacientes continuaron el tratamiento más allá de los 6 meses
El estudio ahora avanzará a la fase de expansión para evaluar el efecto preliminar de la combinación en MTD antes de proceder a una comparación aleatorizada de Fase 2a con el tratamiento estándar en pacientes con PROC.
Sonnet BioTherapeutics (NASDAQ:SONN)는 아테졸리주맙과 함께 사용하는 SON-1010 약물의 긍정적인 안전성 결과를 발표했습니다. 이 약물은 백금 내성 난소암(PROC) 치료에 사용됩니다. 1b/2a 단계의 임상 시험에서 최대 내약 용량(MTD)을 1200 ng/kg으로 설정했으며, 용량 제한 독성이나 사이토카인 방출 증후군 없이 진행되었습니다.
주요 발견 사항은 다음과 같습니다:
- 15명의 평가 가능한 환자 중 5명(33%)이 치료 후 4개월에 걸쳐 안정적인 병세를 보였습니다.
- 한 PROC 환자는 종양 크기가 44% 감소하여 부분 반응을 달성했습니다.
- 일반적인 부작용으로는 피로, 발열 및 위장 증상이 포함되었습니다.
- 15명의 평가 가능한 환자 중 8명(53%)이 첫 번째 추적 조사에서 안정적인 병세를 보였습니다.
- 4명의 환자가 6개월 이상 치료를 지속했습니다.
이 연구는 이제 MTD에서 조합의 초기 효과를 평가하기 위해 확장 단계로 진행되며, 이후 PROC 환자에 대한 표준 치료와의 무작위 비교를 위한 2a 단계로 진행될 것입니다.
Sonnet BioTherapeutics (NASDAQ:SONN) a annoncé des résultats de sécurité positifs pour son médicament SON-1010 en combinaison avec l'atezolizumab pour le traitement du cancer de l'ovaire résistant au platine (PROC). L'essai clinique de Phase 1b/2a a établi une dose maximale tolérée (MTD) de 1200 ng/kg sans toxicité limitante de dose ni syndrome de libération de cytokines.
Les principales conclusions incluent :
- 5 des 15 patients évaluables (33%) ont montré une maladie stable quatre mois après le traitement
- Un patient atteint de PROC a obtenu une réponse partielle avec une réduction de la taille de la tumeur de 44%
- Les effets secondaires courants comprenaient de la fatigue, de la fièvre et des symptômes gastro-intestinaux
- 8 des 15 patients évaluables (53%) ont montré une maladie stable lors du premier suivi
- 4 patients ont poursuivi le traitement au-delà de 6 mois
L'étude avancera maintenant vers la phase d'expansion pour évaluer l'effet préliminaire de la combinaison à la MTD avant de procéder à une comparaison randomisée de Phase 2a avec les soins standard chez les patients atteints de PROC.
Sonnet BioTherapeutics (NASDAQ:SONN) hat positive Sicherheitsresultate für sein Medikament SON-1010 in Kombination mit Atezolizumab zur Behandlung von platinresistentem Ovarialkarzinom (PROC) bekannt gegeben. Die klinische Studie der Phase 1b/2a stellte eine maximale tolerierte Dosis (MTD) von 1200 ng/kg ohne dosislimitierende Toxizität oder Zytokinfreisetzungssyndrom fest.
Wichtige Ergebnisse sind:
- 5 von 15 evaluierbaren Patienten (33%) zeigten vier Monate nach der Behandlung eine stabile Erkrankung
- Ein PROC-Patient erreichte eine partielle Reaktion mit einer Tumorgrößenreduktion von 44%
- Häufige Nebenwirkungen umfassten Müdigkeit, Fieber und gastrointestinale Symptome
- 8 von 15 evaluierbaren Patienten (53%) zeigten beim ersten Follow-up eine stabile Erkrankung
- 4 Patienten setzten die Behandlung über 6 Monate fort
Die Studie wird nun in die Erweiterungsphase übergehen, um die vorläufige Wirkung der Kombination bei MTD zu bewerten, bevor sie in die Phase 2a mit einer randomisierten Vergleichsstudie mit der Standardbehandlung bei PROC-Patienten übergeht.
- Achieved maximum tolerated dose without serious safety concerns
- 33% of patients showed stable disease at 4 months
- One patient achieved partial response with 44% tumor reduction
- Trial advancing to expansion phase following positive safety review
- 53% of evaluable patients showed initial stable disease
- Only one patient achieved partial response out of 19 treated
- Company seeking partnership support for later stage development, suggesting potential funding constraints
Insights
The safety data for Sonnet's SON-1010 (IL12-FHAB) combination therapy represents a potentially significant development in immuno-oncology. Previous attempts to harness IL-12's potent anti-tumor properties have been hampered by severe toxicity issues, particularly cytokine release syndrome. The fact that SON-1010 achieved its maximum tolerated dose (MTD) of 1200 ng/kg in combination with atezolizumab without dose-limiting toxicity is technically impressive.
The early efficacy signals are cautiously encouraging. A partial response in one platinum-resistant ovarian cancer patient (44% tumor reduction plus >2x decrease in CA-125) at the highest dose is noteworthy in this difficult-to-treat population. The 33% stable disease rate at four months across evaluable patients provides additional support for potential clinical benefit.
The mechanism leveraging Sonnet's Fully Human Albumin Binding platform appears to address the historical challenges with IL-12 by extending half-life and potentially enhancing tumor targeting. This approach theoretically allows higher, more efficacious doses to be administered safely.
However, these results remain preliminary. The sample size is small (15 evaluable patients), and larger cohorts will be needed to confirm both safety and efficacy. The advancement to the expansion phase is a positive step, but the critical test will be the Phase 2a randomized comparison against standard care in PROC patients, where response rates with existing therapies remain disappointingly low.
Sonnet's SON-1010 data represents a meaningful clinical milestone for this micro-cap company (
The preliminary efficacy signals—particularly the partial response in platinum-resistant ovarian cancer—could significantly enhance SON-1010's commercial prospects if replicated in larger studies. PROC represents a substantial market opportunity with high unmet need and effective treatment options.
Importantly, management's explicit mention of seeking "partnership opportunities" signals a strategic approach toward addressing the substantial capital requirements for late-stage clinical development. For a company of Sonnet's size, securing a development partner would be crucial for advancing their pipeline and potentially transformative for shareholder value.
The company's FHAB platform technology appears to offer potential advantages in targeting the tumor microenvironment, with the albumin-binding property potentially enabling better targeting and retention in tumors expressing SPARC, a protein abundant in ovarian cancer.
While these results warrant optimism, investors should recognize the early stage of development and historical challenges in translating promising early clinical signals into approved therapies. The advancement to expansion phase reduces near-term clinical risk, but substantial development hurdles remain before commercialization could be considered.
Topline safety data in SB221 study suggest clinical benefit of SON-1010 in combination with atezolizumab (Tecentriq®)
The maximum tolerated dose (MTD) of SON-1010 was set at 1200 ng/kg in combination with atezolizumab in patients with platinum-resistant ovarian cancer (PROC), without dose-limiting toxicity or evidence of cytokine release syndrome at any dose level
Stable disease (SD) at four months post-initiation of dosing was seen in 5 of 15 evaluable patients (
One patient with PROC who was dosed at the MTD had a partial response (PR) by RECIST criteria (
Sonnet management and the lead PI for the SB221 study discuss the safety data in a “What This Means” webinar; Access here
PRINCETON, N.J., April 04, 2025 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing immunotherapeutic drugs targeting the tumor microenvironment (TME), announced today positive safety results of SON-1010 (IL12-FHAB) at the highest dose combined with atezolizumab in the Phase 1b/2a clinical trial in adult patients with advanced solid tumors or platinum-resistant ovarian cancer (PROC) (the SB221 study). Based on positive feedback from a formal evaluation by the Safety Review Committee (SRC) for the SB221 study, the study can now advance to the expansion phase, which will study the preliminary effect of the combination at the MTD, before proceeding to a Phase 2a randomized comparison with the standard of care in patients with PROC. Additionally, the Company announced the release of a “What This Means” webinar discussing the interim SB221 safety data, now available here.
The SB221 study was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of increasing doses of SON-1010 administered with atezolizumab. The primary goal for the first part of the study was to establish the MTD in combination with the immune checkpoint inhibitor (ICI). A total of 19 subjects were treated during dose escalation and one patient with PROC had a partial response at the highest dose.
The SB221 SRC review at the completion of dose expansion in combination with atezolizumab concluded that fatigue, fevers, and gastrointestinal symptoms were the most common adverse effects; no dose-limiting toxicity or cytokine release syndrome were seen. The only related serious adverse event (SAE) during dose escalation was Grade 2 pneumonitis, which is a known adverse event with atezolizumab. One patient with PROC had a
“Platinum resistant ovarian cancer patients remain a very difficult group to treat, and these patients continue to have low response rates to currently approved therapies,” said Robert Wenham, M.D., Chair of the Department of GYN Oncology at Moffitt Cancer Center and the study’s lead Principal Investigator. “It has been difficult to show efficacy using existing immune drugs like checkpoint inhibitors. This patient’s tumor reduction using an ICI in combination with a novel extended PK IL-12 immune therapeutic is exciting. We are looking forward to entering the next stage of the SB221 trial.”
SON-1010 may work best with an ICI, particularly with immunologically ‘cold’ tumors that are high in secreted protein acidic and rich in cysteine (SPARC), such as ovarian cancer. Binding to native albumin in the serum extends the half-life and bioactivity of the IL-12 component, which also allows targeting of and retention in the TME by strong binding to gp60 and SPARC. Safety has been a concern since the initial Phase 2 study of rhIL-12 in the late 1990’s, where daily dosing led to severe adverse effects. While safer dosing strategies have since been developed with rhIL-12, the promise of improved tumor control in humans has not been achieved using doses that are also demonstrated to be safe. Linking the IL-12 to a fully human single chain variable fragment (scFv) that binds albumin and extends the half-life may finally allow higher doses that are potentially more effective to be given safely. The preclinical and mechanistic characterization of SON-1010, the Company’s proprietary version of recombinant human interleukin-12 (rhIL-12) configured using genetic fusion to Sonnet's Fully Human Albumin Binding (FHAB®) platform, was recently published here.
“We are encouraged by the topline safety data and very pleased with the ovarian cancer PR in the Phase 1b portion of the SB221 study. Given the history of safety concerns with rhIL-12, it is exciting to see higher doses of SON-1010 demonstrating minimal toxicity when used in combination with atezolizumab,” added Richard Kenney, M.D., Sonnet's Chief Medical Officer. “We may finally be able to realize the promising antitumor effect that has been associated with this cytokine in preclinical models for decades. While the clinical benefit we have seen during dose escalation has been reassuring, the PR at the highest dose is particularly important, as this suggests that there may be a synergistic therapeutic effect in combination with checkpoint inhibitors or chemotherapy.”
All enrolled patients have advanced solid tumors and all patients at the higher doses have PROC, including those enrolled in a final 1200 ng/kg dose-escalation cohort. The SB221 trial employed a ‘desensitizing’ first dose of 300 ng/kg to take advantage of the known tachyphylaxis with rhIL-12, with the intention of minimizing toxicity while allowing for higher maintenance doses. The safety and toxicity profile that has developed is typical for a Phase 1 oncology trial, with the majority of adverse events (AEs) being reported as mild and transient and there has been no evidence of cytokine release syndrome. Of the 19 patients dosed to date, 8 of the 15 evaluable patients (
“This topline safety data release from our atezolizumab combination program is another significant milestone for Sonnet’s clinical development,” concluded Raghu Rao, Sonnet’s Interim Chief Executive Officer. “Safety of this extended PK version of IL-12 has been within expected levels and the comparison with dosing in healthy volunteers provided strong evidence of tumor targeting and accumulation in humans. We have used this trial to establish the MTD of combination with an ICI and will continue to follow the patients currently being treated to assess longer-term safety and tumor responses. Sonnet continues to seek partnership opportunities to help support later stage development of SON-1010.”
For more information about the Phase 1b/2a SB221 study in adult patients with advanced solid tumors or PROC, visit www.clinicaltrials.com and reference identifier NCT05756907. Tecentriq® (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.
About SON-1010
SON-1010 is a candidate immunotherapeutic recombinant drug that links unmodified single-chain human IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. This single-chain antibody fragment was selected to bind albumin both at normal pH, as well as at the acidic pH typically found in the TME. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only IL-12, but a variety of potent immunomodulators that can be linked using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as SPARC and GP60, several types of cancer, such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant to this approach. SON-1010 is designed to deliver IL-12 to local tumor tissue, turning ‘cold' tumors ‘hot' by stimulating IFN, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells.
About the SB221 Phase 1b/2a Trial
SB221 is a global Phase 1b/2a multicenter, dose-escalation and randomized proof-of-concept study to assess the safety, tolerability, PK, PD, and efficacy of SON-1010 administered subcutaneously (SC), either alone or in combination with atezolizumab given intravenously (IV). The study is designed in Part 1 to rapidly establish the maximum tolerated dose (MTD) of the combination, starting in patients with advanced solid tumors and moving to PROC in small dose-escalation groups, then to expand the dataset at the recommended Phase 2 dose (RP2D) to show the likelihood of efficacy in PROC using a standard 2-stage design. This would be followed in Part 2 by an assessment in patients with PROC of the potential for improved efficacy of the combination over SON-1010 alone or the standard of care. Both Sonnet and Roche look forward to this collaboration as an opportunity to improve outcomes for patients with ovarian cancer.
About Sonnet BioTherapeutics Holdings, Inc.
Sonnet is an oncology-focused biotechnology company with a proprietary platform for developing targeted biologic drugs with single or bifunctional action. Known as FHAB (Fully Human Albumin-Binding), the technology utilizes a fully human single chain antibody fragment (scFv) that binds to and "hitch-hikes" on human serum albumin (HSA) for transport to target tissues. Sonnet's FHAB was designed to specifically target tumor and lymphatic tissue, with an improved therapeutic window for optimizing the safety and efficacy of immune modulating biologic drugs. FHAB platform is the foundation of a modular, plug-and-play construct for potentiating a range of large molecule therapeutic classes, including cytokines, peptides, antibodies and vaccines.
Sonnet’s lead program, SON-1010, or IL-12-FHAB, is in development for the treatment of solid tumors, certain types of sarcoma, and ovarian cancer. SON-1010 is being evaluated in an ongoing Phase 1/2a study through a Master Clinical Trial and Supply Agreement, along with ancillary Quality and Safety Agreements, with Roche in combination with atezolizumab (Tecentriq®) for the treatment of platinum-resistant ovarian cancer (PROC) (NCT05756907). The Company is also evaluating its second program using this platform, SON-1210, an IL12-FHAB-IL15 for solid tumors, in collaboration with the Sarcoma Oncology Center to commence an investigator-initiated and funded Phase 1/2a study for the treatment of pancreatic cancer.
Forward-Looking Statements
This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the outcome of the Company’s clinical trials, the Company's cash runway, the Company's product development, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions.
These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential," "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
Investor Relations Contact:
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FAQ
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