This is a Phase 1b/2a, open-label, adaptive-design outpatient study to assess the safety, tolerability, and PK/PD of SON-1010 in combination with atezolizumab administered to patients with advanced solid tumors (Part 1) and patients with Platinum-resistant Ovarian Cancer (Part 2)

开始日期2023-09-15

申办/合作机构

Sonnet BioTherapeutics, Inc.

[+1]

NCT05408572

/ Completed早期临床1期

A Phase 1, Randomized, Adaptive-Design, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SON-1010 (IL12-FHAB) in Healthy Adults

SB102 is a randomized, double-blind, single center, placebo-controlled study in healthy adults starting with sentinel participants at each dose level to carefully assess the safety, tolerability, PK, and PD of SON-1010.

开始日期2022-07-27

申办/合作机构

Sonnet BioTherapeutics, Inc.

NCT05352750

/ Recruiting临床1期

A Phase 1, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SON-1010 (IL12-FHAB) in Adult Patients With Advanced Solid Tumors.

This is a Phase 1, first-in-human, open-label, adaptive-design outpatient study to assess the safety, tolerability, and PK/PD of SON-1010 administered to patients with advanced solid tumors.

开始日期2022-04-20

申办/合作机构

Sonnet BioTherapeutics, Inc.

100 项与 SON-1010 相关的临床结果

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100 项与 SON-1010 相关的转化医学

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100 项与 SON-1010 相关的专利（医药）

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项与 SON-1010 相关的文献（医药）

Frontiers in immunology

A phase I trial of SON-1010, a tumor-targeted, interleukin-12-linked, albumin-binding cytokine, shows favorable pharmacokinetics, pharmacodynamics, and safety in healthy volunteers

Article

作者: Cini, John K ; Kuan, Isabelle ; Lickliter, Jason ; Ryan, Philip J ; Polasek, Thomas M ; Chawla, Sant P ; Kenney, Richard T ; Dexter, Susan ; DaFonseca, Manuel ; Bingham, Justus

Background:

The benefits of recombinant interleukin-12 (rIL-12) as a multifunctional cytokine and potential immunotherapy for cancer have been sought for decades based on its efficacy in multiple mouse models. Unexpected toxicity in the first phase 2 study required careful attention to revised dosing strategies. Despite some signs of efficacy since then, most rIL-12 clinical trials have encountered hurdles such as short terminal elimination half-life (T½), limited tumor microenvironment targeting, and substantial systemic toxicity. We developed a strategy to extend the rIL-12 T½ that depends on binding albumin in vivo to target tumor tissue, using single-chain rIL-12 linked to a fully human albumin binding (FHAB) domain (SON-1010). After initiating a dose-escalation trial in patients with cancer (SB101), a randomized, double-blind, placebo-controlled, single-ascending dose (SAD) phase 1 trial in healthy volunteers (SB102) was conducted.

Methods:

SB102 (NCT05408572) focused on safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) endpoints. SON-1010 at 50-300 ng/kg or placebo administered subcutaneously on day 1 was studied at a ratio of 6:2, starting with two sentinels; participants were followed through day 29. Safety was reviewed after day 22, before enrolling the next cohort. A non-compartmental analysis of PK was performed and correlations with the PD results were explored, along with a comparison of the SON-1010 PK profile in SB101.

Results:

Participants receiving SON-1010 at 100 ng/kg or higher tolerated the injection but generally experienced more treatment-emergent adverse effects (TEAEs) than those receiving the lowest dose. All TEAEs were transient and no other dose relationship was noted. As expected with rIL-12, initial decreases in neutrophils and lymphocytes returned to baseline by days 9-11. PK analysis showed two-compartment elimination in SB102 with mean T½ of 104 h, compared with one-compartment elimination in SB101, which correlated with prolonged but controlled and dose-related increases in interferon-gamma (IFNγ). There was no evidence of cytokine release syndrome based on minimal participant symptoms and responses observed with other cytokines.

Conclusion:

SON-1010, a novel presentation for rIL-12, was safe and well-tolerated in healthy volunteers up to 300 ng/kg. Its extended half-life leads to a prolonged but controlled IFNγ response, which may be important for tumor control in patients.

Clinical trial registration:

https://clinicaltrials.gov/study/NCT05408572, identifier NCT05408572.

Frontiers in Immunology

SON-1010: an albumin-binding IL-12 fusion protein that improves cytokine half-life, targets tumors, and enhances therapeutic efficacy

Article

作者: McAndrew, Stephen J ; Cini, John K ; Boohaker, Rebecca ; Lapi, Suzanne E ; Brody, Rich ; Eraslan, Rukiye-Nazan ; Kenney, Richard T ; Mohan, Pankaj ; Dexter, Susan ; Rezac, Darrel J

Background:

Cytokines have been promising cancer immunotherapeutics for decades, yet only two are licensed to date. Interleukin-12 (IL-12) is a potent regulator of cell-mediated immunity that activates NK cells and interferon-γ (IFNγ) production. It plays a central role in multiple pathways that can enhance cancer cell death and modify the tumor microenvironment (TME). Attempts to dose rIL-12 were initially successful but IFNγ toxicity in Phase 2 complicated further development in the late 1990s. Since then, better dosing strategies have been developed, but none have achieved the level of cancer control seen in preclinical models. We set out to develop a novel strategy to deliver fully functional IL-12 and other biologics to the TME by binding albumin, taking advantage of its ability to be concentrated and retained in the tumor.

Methods:

Single-chain variable fragments (scFv) were identified from a human phage display library that bound human, mouse, and cynomolgus macaque serum albumin, both at physiologic and acidic conditions. These were taken through a series of steps to identify strongly binding molecules that don’t interfere with the normal physiology of albumin to bind FcRn, giving it prolonged half-life in serum, along with SPARC/GP60, which allows albumin to target the TME. A final molecule was chosen and a single mutation was made that minimizes the potential for immunogenicity. This fully human albumin-binding (FHAB®) domain was characterized and manufacturing processes were developed to bring the first drug candidate into the clinic.

Results:

Once identified, the murine form of mIL12-FHAB was studied preclinically to understand its mechanism of action and biodistribution. It was found to be much more efficient at blocking tumor growth compared to murine IL-12, while stimulating significant IFNγ production with minimal toxicity. SON-1010, which uses the human IL-12 sequence, passed through all of the characterization and required toxicology and is currently being studied in the clinic.

Conclusions:

We identified and developed a platform technology with prolonged half-life that can target IL-12 and other immune modulators to the TME. Safety and efficacy are being studied using SON-1010 as monotherapy and in combination with checkpoint blockade strategies.

项与 SON-1010 相关的新闻（医药）

2025-04-16

·sonnetbio.com

Sonnet Releases Virtual Investor "What This Means" Segment

- Raghu Rao, Interim Chief Executive Officer and Dr. Richard Kenney, Chief Medical Officer, of Sonnet discuss the recently announced safety data related to SON-1010 - Watch the "What This Means" video here PRINCETON, N.J., April 16, 2025 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing immunotherapeutic drugs targeted to the tumor microenvironment (TME), today announced that members of the Sonnet management team participated in a Virtual Investor "What This Means" segment. As part of the segment, Raghu Rao, Interim Chief Executive Officer and Dr. Richard Kenney, Chief Medical Officer, discussed the recently announced positive safety results of SON-1010 (IL12-FHAB) at the highest dose combined with atezolizumab being evaluated in the Phase 1b/2a clinical trial in adult patients with advanced solid tumors or platinum-resistant ovarian cancer (PROC) (the SB221 study). Mr. Rao and Dr. Kenney also provided insight into next steps for the program. The Virtual Investor "What This Means" segment featuring Sonnet is now available here. 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: JTC Team, LLC Jenene Thomas 908-824-0775 SONN@jtcir.com Released April 16, 2025

免疫疗法临床研究

2025-04-11

·癌度

《癌度早报2025年4月11日》

癌度临床试验病友交流群（点击）一、新药快讯1、抗体偶联药HS-20093第三次被纳入突破性治疗2025年4月9日，CDE官网显示，国产抗体偶联药HS-20093拟纳入突破性治疗品种，用于既往经过含铂化疗后进展或复发的驱动基因阴性的局部晚期或转移性非鳞状非小细胞肺癌。该药的一项一期临床试验结果表明，HS-20093在小细胞肺癌、非小细胞肺癌和肉瘤中观察到了初步临床活性，并确认了多种缓解，且安全性可控。2、靶向PD-1和TIGIT的双抗药首次启动肝细胞癌的三期临床试验2025年4月9日，药物临床试验登记与信息公示平台官网显示，Rilvegostomig 联合贝伐珠单抗伴或不伴替西木单抗一线治疗肝细胞癌的III期研究启动，这是该药首个启动的肝细胞癌三期临床试验，这项研究预计国内入组310人，且该药在胆道癌、非小细胞肺癌、胃癌也开展了三期临床试验。3、SON-1010联合免疫药物阿替利珠单抗对卵巢癌展现初步疗效根据一项公布的临床试验结果，前沿药SON-1010联合PD-L1抑制剂阿替利珠单抗，治疗铂类耐药卵巢癌和其他晚期实体瘤显示出积极的临床活性，并且安全性良好。SON-1010是一种新型免疫治疗药物，15名可评估治疗效果的晚期实体瘤患者中，53%的患者在首次随访CT检查时发现病情稳定，33%的患者在4个月时仍然处于病情稳定状态。二、抗癌前沿1、靶向药联合免疫治疗KRAS基因G12C，获益和风险并存2025年欧洲肺癌大会上，有几项研究成果公布。阿达格拉西联合PD-1帕博利珠单抗对于KRAS基因G12C突变且PD-L1表达超50%的肺癌表现出积极疗效，客观缓解率达到了59%，中位缓解持续时间为26.3个月，中位无进展生存时间达到了27.7个月，但是这种联合治疗的毒性较高，因此联合治疗仅仅适合身体状况良好的患者。另一款靶向药氟泽雷塞联合EGFR抗体药西妥昔单抗对于KRAS基因G12C突变肺癌的治疗应答率达到了80%，中位无进展生存时间为12.5个月，似乎这种联合不如靶向药联合PD-1效果更好，但是不良反应会低一些。

临床3期免疫疗法突破性疗法临床结果

2025-04-08

·癌度

《癌度早报2025年4月8日》

癌度临床试验病友交流群（点击）一、新药快讯1、国产双特异性抗体药PT217获批临床，治疗实体瘤2025年4月7日，DLL3和CD47双特异性抗体药PT217已获得中国国家药品监督管理局药品审评中心（CDE）批准开展2期联合治疗临床试验，该药将会与化疗或PD-L1抑制剂联合治疗小细胞肺癌和其他神经内分泌癌，包括前列腺神经内分泌癌的安全性和治疗效果。2、新疗法PIPAC-MMC联合化疗，治疗肠癌显示积极疗效2025年美国外科肿瘤学会年会上，一项一期临床试验公布研究结果，新疗法PIPAC-MMC联合全身化疗，在一部分无法手术切除的结直肠癌和阑尾癌腹膜转移患者中，展现出积极的疗效和良好的耐受性。PIPAC-MMC是一种治疗癌症腹膜转移的新型局部化疗方法，19名患者中1名患者病灶全消失，2名患者病灶缩小30%以上，12名患者病情稳定。3、新药SON-1010治疗晚期肉瘤展现较好安全性和初步疗效最近，公布的一项临床试验结果表明，前沿药SON-1010治疗晚期肉瘤，包括平滑肌肉瘤或脂肪肉瘤，显示出良好的安全性和初步疗效。晚期肉瘤患者中，SON-1010联合化疗药曲贝替定，未发现任何意料之外的安全性。SON-1010单药治疗的6名患者，5名患者治疗4个月病情稳定，SON-1010剂量递增阶段的24名患者，13名表现出临床获益的迹象。二、新药快讯1、沈琳教授科研成果，NOTCH1基因状态对晚期食管鳞癌疗效预测2025年4月3日，北京大学肿瘤医院沈琳教授在《临床肿瘤学杂志》发表了一篇研究，基于一项三期临床试验结果，揭示了NOTCH1基因突变在晚期或转移性食管鳞癌接受PD-1单抗治疗的价值，在22%的携带NOTCH1基因突变的患者中，免疫治疗药物中位总生存时间是18.4个月，而化疗组的中位总生存时间是5.3个月，NOTCH1突变或有助于筛选可能从抗PD-1治疗中获益的患者。

临床3期临床2期免疫疗法临床结果

100 项与 SON-1010 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床2期	美国	Sonnet BioTherapeutics, Inc.	2023-09-15
晚期恶性实体瘤	临床2期	美国	Hoffmann-La Roche Ltd.	2023-09-15
晚期恶性实体瘤	临床2期	澳大利亚	Hoffmann-La Roche Ltd.	2023-09-15
晚期恶性实体瘤	临床2期	澳大利亚	Sonnet BioTherapeutics, Inc.	2023-09-15
铂耐药性卵巢癌	临床2期	美国	Hoffmann-La Roche Ltd.	2023-09-15
铂耐药性卵巢癌	临床2期	美国	Sonnet BioTherapeutics, Inc.	2023-09-15
铂耐药性卵巢癌	临床2期	澳大利亚	Hoffmann-La Roche Ltd.	2023-09-15
铂耐药性卵巢癌	临床2期	澳大利亚	Sonnet BioTherapeutics, Inc.	2023-09-15
软组织肉瘤	临床1期	美国	Sonnet BioTherapeutics, Inc.	-

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05352750 (SB101, GlobeNewswire \| Company_Website) 人工标引	临床1期	实体瘤	24	SON-1010	鏇憲願蓋膚構網衊齋衊(餘壓膚網膚遞繭齋願艱) = 鏇糧艱鑰壓觸餘糧獵築襯遞繭選齋淵獵蓋獵蓋 (選衊觸襯襯襯齋鑰廠蓋 ) 更多	积极	2024-12-09
NCT05408572 (SB102, Literature \| Pubmed \| Front Immunol) 人工标引	临床1期	-	-	SON-1010	鹹糧鬱餘積鏇糧齋壓廠(繭觸簾繭襯願製窪製鬱) = two-compartment elimination in SB102 with mean T½ of 104 h, compared with one-compartment elimination in SB101 襯觸膚齋觸憲壓築鏇壓 (築鏇鬱窪廠艱糧顧繭醖 )	积极	2024-02-29
AACR2023 人工标引	N/A	HR阳性/HER2低表达实体瘤	11	SON-1010	醖齋鑰蓋鏇鏇構獵膚淵(網艱餘廠範膚獵選蓋遞) = 衊繭淵夢糧鬱願鏇鬱築築廠醖夢艱積願醖獵願 (齋夢積製糧製襯艱繭淵 ) 更多	积极	2023-04-14
AACR2023 人工标引	N/A	HR阳性/HER2低表达实体瘤	11	SON-1010 (the first 3 dose cohorts)	範夢顧網壓夢憲窪鹽積(顧顧積構構範築壓鹽鏇) = 築獵糧積餘衊壓廠積壓壓觸餘遞餘繭觸遞網繭 (選獵鏇糧壓觸遞構齋鹽 )	积极	2023-04-14
NCT05352750 (SB101, Corporate Publications) 人工标引	临床1期	肿瘤	12	SON-1010	願築鏇簾艱鬱鏇衊鏇製(窪餘鹹襯鏇願鹽鹹範餘) = mild/moderate, transient in nature, and have all been tolerable 網顧鹽範觸襯獵夢醖遞 (鹽窪膚襯繭鹽簾憲製蓋 )	积极	2022-11-02