A Phase 2a, Single-dose, Open-label Study to Evaluate Diagnostic Performance and Safety of Pegsitacianine, an Intraoperative Fluorescence Imaging Agent for the Detection of Cancer, in Patients With Unknown Primary Head and Neck Cancer (ILLUMINATE STUDY)

This is a non-randomized, open-label, single-center, safety and imaging feasibility study of Pegsitacianine, an intraoperative fluorescence imaging agent.

开始日期2024-04-17

申办/合作机构

The University of Texas Southwestern Medical Center

[+1]

NCT05048082

/ Completed临床2期

A Phase 2, Single-Dose, Open-Label Study to Evaluate Diagnostic Performance and Safety of Pegsitacianine, an Intraoperative Fluorescence Imaging Agent for the Detection of Lung Malignancies, in Patients Undergoing Routine Surgery

This Phase 2 study is an open-label, single-arm trial where each patient is his/her own "intrapatient" control. All patients will receive a single dose of pegsitacianine prior to standard of care surgery.

开始日期2022-04-13

申办/合作机构

OncoNano Medicine, Inc.

NCT04950166

/ Completed临床2期

A Phase 2, Open-Label Study to Evaluate the Performance and Safety of ONM100, an Intraoperative Fluor Imaging Agent for the Detection of Peritoneal Mets

Peritoneal carcinomatosis (PC) results from the metastasis of a primary cancer of the peritoneum (e.g., appendiceal, ovarian, uterine, colorectal, and gastric cancers) that then disseminates throughout the abdominal cavity. Historically progression to PC was considered terminal and resulted in survival times on the scale of a few months with palliative care being the best option for patients. More recently, cytoreductive surgery (CS) has emerged as a means to prolong and improve patient lives with a median increase in survival of up to
5 years. It has been reported that for every 10% increase in cytoreduction there is a 5.5% increase in median survival time. In addition to surgical tumor debulking within the peritoneal space, it has also been shown that coupling surgical intervention with hyperthermic intraperitoneal chemotherapy (HIPEC) can have an even greater impact on patient outcomes. Pegsitacianine, a micellar fluorescence agent, exploits the ubiquitous pH differences observed between cancerous and normal tissues. This in turn, provides a highly sensitive and specific fluorescence response after localizing within the tumor microenvironment, thus allowing the detection of primary tumors, their margins, metastatic disease, and tumor-containing lymph nodes.

开始日期2021-11-30

申办/合作机构

OncoNano Medicine, Inc.

100 项与 Pegsitacianine 相关的临床结果

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100 项与 Pegsitacianine 相关的转化医学

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100 项与 Pegsitacianine 相关的专利（医药）

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项与 Pegsitacianine 相关的文献（医药）

2026-01-01·IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING

Single-Operator Cancer Vision Goggles for Quantitative Near-Infrared Fluorescence-Guided Oncologic Surgery

Article

作者: Hite, Henry ; Jovan, Jaden ; Leu, William ; Achilefu, Samuel ; Nussinov, Zohar ; Gautam, Krishna Sharmah ; Sumer, Baran ; Li, Fangchen ; Xu, Xiao ; Zurutuza, Ian ; Trivedi, Varun ; Akers, Walter J. ; Dunn, John ; Buras, William ; Seidel, Alexander ; Blasi, Nicole ; Ta, Christopher ; Shen, Mutian ; Gao, Jinming ; Hongsermeier, Cody ; Zhang, Haini

OBJECTIVE:

Near-infrared fluorescence (NIRF) imaging systems often require multiple operators and lack standardized acquisition constraints, limiting reproducibility across users and sites. We present a single-operator, wearable Cancer Vision Goggles (CVG) platform for hands-free NIRF guidance while preserving a radiometrically faithful reference stream for quantitative analysis.

METHODS:

The head-mounted binocular CVG integrates synchronized visible/NIR cameras, real-time co-registration to an optical see-through display, green alignment lasers converging at a preset 50-cm distance to standardize geometry, and a posture-dependent laser safety interlock. A Bluetooth foot pedal and graphical user interface enable hands-free paired laser-on/laser-off snapshot capture. Performance was characterized using USAF targets and ICG Intralipid phantoms, and validated in vivo in a 4T1 murine tumor model using LS301-HSA and in the operating room by ex vivo imaging of head and neck cancer specimens from patients injected with Pegsitacianine.

RESULTS:

At 50 cm, spatial resolution was 281 μm; the excitation field exhibited peak irradiance of 26.4 ± 2.2 mW/cm2 with 73.8 ± 3.2 mm FWMH. Phantom studies achieved signal-to-background ratio (SBR) >1 at 100 pM (raw Bayer) and 300 pM (Y-luminance), with linear behavior at low-to-moderate concentrations. Murine tumors and human specimens demonstrated consistent tumor-associated NIRF localization. Real-time dynamic thresholding enhanced tumor-background delineation and on-display reporting of fluorescence metrics for data-driven guidance.

CONCLUSION:

This CVG platform offers a wearable, single-operator NIRF imaging system that combines distance-enforced acquisition, integrated safety, a hands-free workflow, and dual-spectral imaging, preserving a radiometrically linear reference for quantitative analysis.

SIGNIFICANCE:

Standardized acquisition supports reproducible fluorescence imaging and analyzable translational datasets.

2024-08-01·MOLECULAR IMAGING AND BIOLOGY

A Phase 2 Multicenter Clinical Trial of Intraoperative Molecular Imaging of Lung Cancer with a pH-Activatable Nanoprobe

Article

作者: Desphande, Charuhas ; Kennedy, Gregory T ; Singhal, Sunil ; Azari, Feredun S ; Chang, Austin ; Predina, Jarrod ; Olson, Madeline ; Delikatny, Edward J ; Bou-Samra, Patrick ; Rice, David C

PURPOSE:

Intraoperative molecular imaging (IMI) uses tumor-targeted optical contrast agents to improve identification and clearance of cancer. Recently, a probe has been developed that only fluoresces when activated in an acidic pH, which is common to many malignancies. We report the first multicenter Phase 2 trial of a pH-activatable nanoprobe (pegsitacianine, ONM-100) for IMI of lung cancer.

METHODS:

Patients with suspected or biopsy-confirmed lung cancer scheduled for sublobar resection were administered a single intravenous infusion of pegsitacianine (1 mg/kg) one to three days prior to surgery. Intraoperatively, the patients underwent a white light thoracoscopic evaluation, and then were imaged with an NIR thoracoscope to detect tumor fluorescence. The primary study endpoint was the proportion of patients with a clinically significant event (CSE) which was defined as an intraoperative discovery during IMI that led to a change in the surgical procedure. Possible CSEs included (i) localizing the index lung nodule that could not be located by white light, (ii) identifying a synchronous malignant lesion, or (iii) recognizing a close surgical margin (< = 10 mm). Secondary endpoints were sensitivity, specificity, NPV, and PPV of pegsitacianine in detecting tumor-containing tissue. The safety evaluation was based on adverse event reporting, clinical laboratory parameters, and physical examinations.

RESULTS:

Twenty patients were confirmed as eligible and administered pegsitacianine. Most of the patients were female (n = 12 [60%]), middle-aged (mean age 63.4 years), and former smokers (n = 13 [65%], 28.6 mean pack years). Mean lesion size was 1.9 cm, and most lesions (n = 17 [85%]) were malignant. The most common histologic subtype was adenocarcinoma (n = 9). By utilizing IMI with pegsitacianine, one patient had a CSE in the detection of a close margin and another had localization of a tumor not detectable by traditional surgical means. Six of 19 (31.6%) malignant lesions fluoresced with mean tumor-to-background ratio (TBR) of 3.00, as compared to TBR of 1.20 for benign lesions (n = 3). Sensitivity and specificity of pegsitacianine-based IMI for detecting malignant tissue was 31.6% and 33.3%, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of pegsitacianine-based IMI was 75% and 7.1%, respectively. Pegsitacianine-based imaging was not effective in differentiating benign and malignant lymph nodes. From a safety perspective, no drug-related serious adverse events occurred. Four patients experienced mild pegsitacianine-related infusion reactions which required discontinuing the study drug with complete resolution of symptoms.

CONCLUSIONS:

Pegsitacianine-based IMI, though well tolerated from a safety perspective, does not consistently label lung tumors during resection and does not provide significant clinical benefit over existing standards of surgical care. The biology of lung tumors may not be as acidic as other solid tumors in the body thereby not activating the probe as predicted.

2024-07-01·Annals of surgical oncology

Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using Pegsitacianine, a pH-Sensitive Imaging Agent: Final Results from a Phase II Study

Article

作者: Fleming, Nicole D ; Madajewski, Brian ; Kim, Alex C ; Levine, Edward A ; Shen, Perry ; Karakousis, Giorgos C ; Westin, Shannon N ; Berry, Laurel K ; Bartlett, David L ; Krishnan, Kartik ; Tanyi, Janos L ; Olson, Madeline T ; Balch, Charles M ; Ostrander, Brian ; Wagner, Patrick

BACKGROUND:

For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such as tumors, resulting in localized fluorescence unmasking. We assessed the utility of pegsitacianine in detecting residual disease following CRS.

PATIENTS AND METHODS:

NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24-72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance.

RESULTS:

A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients.

CONCLUSIONS:

Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS.

项与 Pegsitacianine 相关的新闻（医药）

2024-04-10

·BioSpace

OncoNano Medicine Presents Preclinical Data for ON-BOARD™ IL-12 Program at AACR Annual Meeting 2024

- muONM-412 significantly improved tolerability over unencapsulated IL-12Fc and showed potent anti-tumor efficacy in mice - ONM-412 demonstrates the potential for clinical translation of the ON-BOARD™ platform SOUTHLAKE, Texas--(BUSINESS WIRE)-- OncoNano Medicine, Inc. presented a late-breaking poster detailing the preclinical efficacy and safety of muONM-412, an ON-BOARD™ nanoparticle-encapsulated murine interleukin-12 fusion protein (IL-12Fc), and in vitro characterization of ONM-412, encapsulating human IL-12Fc, at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego, California. Despite its potent pleiotropic and well-established anti-cancer effects, the clinical application of IL-12 has been hindered by significant adverse toxicities. OncoNano developed ON-BOARD™, an ultra-pH sensitive nanoparticle platform, to shield payloads from systemic exposure and target solid tumors by responding to the highly acidic tumor microenvironment. Encapsulation of payloads like IL-12 by ON-BOARD™ may provide the opportunity to improve the therapeutic index of a variety of anti-cancer therapies. “As part of the study presented at AACR, the preclinical safety and activity of muONM-412 were evaluated with the data demonstrating it significantly improved tolerability over unencapsulated IL-12Fc while showing potent antitumor efficacy in mice. Findings also reveal that ONM-412 illustrates favorable stability and pH-responsive IL-12 bioactivity in vitro,” said Tian Zhao, Ph.D., Vice President of Research and Development for OncoNano Medicine. “We believe our ON-BOARD™ ultra-pH sensitive micelle technology can transform the targeted delivery of oncology therapeutics and look forward to continuing the development of new treatments for patients with cancer.” muONM-412 key findings: Exhibited improved tolerability in vivo compared to unencapsulated IL-12Fc through the observation of reduced body weight loss, absence of liver toxicity and lower plasma IFNy levels. Induced tumor immune remodeling, with increased infiltration by IFNγ+ and GzmB+ CD8 T and NK cells. Strong dose-responsive anti-tumor efficacy shown in MC38 tumor-bearing animals. ONM-412 key findings: Demonstrated high encapsulation efficiency (>85%) in uniformly distributed particles (Dh<50nm) with 12-month on-going shelf-life stability. Rapid and complete recovery of IL-12 bioactivity shown <10 minutes after acid-activation. Confirmed pH-specific release in vitro with a >100-fold activation window between the acid-activated and intact formulations by a HEK reporter assay and an IFNγ induction assay. Presentation Overview: TITLE: Preclinical characterization of ONM-412, an ultra-pH sensitive nanoparticle encapsulated IL-12 fusion protein PRESENTER: Jason Miller, Ph.D., Associate Director, Research Pipeline Development, OncoNano Medicine Link to the poster may be found on the OncoNano Medicine website at: News - OncoNano Medicine. About OncoNano Medicine OncoNano Medicine is developing a new class of cancer therapeutics that exploit pH to diagnose and treat solid tumors with high specificity. OncoNano’s ON-BOARD™ platform is generating a robust oncology pipeline to support novel therapeutic development for patients with high unmet medical needs. Our polymeric micelles are designed to efficiently deliver oncology payloads to the tumor microenvironment for an enhanced therapeutic index. Our product candidates and interventions are designed to help patients across the continuum of cancer care including a platform of immuno-oncology therapeutics that activate and guide the body’s immune system to target cancer and agents for real-time image guided surgery. ONM-501, OncoNano’s first therapeutic program is a next generation dual-activating STING (STimulator of INterferon Genes) agonist currently in phase 1 studies. ONM-412, the highly potent pro-inflammatory cytokine, interleukin-12 (IL-12), encapsulated in the ON-BOARD™ ultra-pH sensitive micelle system is currently in preclinical development along with other novel targets. Additionally, the ON-BOARD™ platform has been used for pegsitacianine, a fluorescent nanoprobe that is being studied as a real-time surgical imaging agent for use in multiple cancer surgeries and is advancing towards a pivotal clinical trial to aid in tumor detection of peritoneal carcinomatosis. The work of OncoNano is supported through grants from the Cancer Prevention & Research Institute of Texas. Learn more about OncoNano’s platform and pipeline at .

临床1期AACR会议临床结果免疫疗法

2024-04-09

·生物谷

Nat Biomed Eng｜癌细胞或能形成保护性“酸壁”从而抵御机体免疫细胞的狙杀

细胞外环境pH值会深刻影响着无数分子相互作用、细胞功能以及生理过程的精密平衡，因此成为生命体系中严密调控的对象。然而在肿瘤中，癌细胞代谢失调和血管供应不足会引起肿瘤微环境呈现酸性。近日，一篇发表在国际杂志Nature Biomedical Engineering上题为“Severely polarized extracellular acidity around tumour cells”的研究报告中，来自德克萨斯大学西南医学中心等机构的科学家们通过研究发现，癌细胞释放的酸要比以往认知的浓度高得多，进而构建起一道“酸壁”（acid wall），有效阻碍免疫细胞对肿瘤的攻击。这一开创性发现为研发旨在调节肿瘤周边酸性环境的新型抗癌疗法奠定了坚实基础。研究者Jinming Gao说道，本文研究揭示了癌细胞周围普遍存在的一种此前并未被认识到的极端细胞外酸性现象。近一个世纪以前，科学家们已经知道，肿瘤是酸性的，也就是说，肿瘤内部的pH值低于7，但仅比体内大多数健康组织略低，比如，人体肌肉在静息状态下的平均pH值大约为7.4，但人类恶性肿瘤的平均pH大约为6.8。几年前，研究人员设计出了一组纳米颗粒，其能在特定的酸度水平下发光，他们发现了一种名为pegsitacianine的纳米颗粒，其能在肿瘤中发出明亮的荧光（在pH为5.3时发光），这种纳米颗粒如今已经通过了第二阶段的临床试验，作为图像引导癌症手术的有效工具。2023年，pegsitacianine获得了FDA的突破性疗法认证，进一步加快了有前景的药物的研发和审查，然而研究者Gao认为，目前我们还并不清楚为何pegsitacianine会发出荧光，因为肿瘤的酸性被认为太过于温和而不足以诱发其激活。癌细胞或能形成保护性“酸壁”从而抵御机体免疫细胞的狙杀图片来源：Nature Biomedical Engineering (2024). DOI:10.1038/s41551-024-01178-7为了回答这一问题，研究人员利用pegsitacianine探针对来自多种人类和小鼠癌症类型的单一细胞样本进行成像，包括肺癌、乳腺癌、黑色素瘤和胶质母细胞瘤。出人意料的是，探针在癌细胞一侧显现出荧光，而在另一侧则无明显信号，揭示了癌细胞内部酸性分布可能存在显著极化现象。这种局部酸性主要来源于癌细胞摄取葡萄糖后产生的乳酸代谢废物。当在肿瘤组织中进行类似的实验时，成像研究结果表明，癌细胞会优先将酸从邻近的癌细胞中抽走并泵入细胞外环境，从而就会在肿瘤边缘形成一种更高酸度的区域。对来自人类肿瘤的样本进行分析后，研究者发现，在肿瘤中这种酸壁几乎没有CD8+ T细胞（一种能抵御癌症的已知免疫细胞类型），当研究人员在酸化至5.3的培养皿中培养癌细胞和CD8+ T细胞时，癌细胞依然生机勃勃，而CD8+ T细胞则会在3小时内死亡，这有力证明，极度酸性环境不仅能够有效阻挡免疫细胞对肿瘤的进攻，而且对癌细胞自身并无显著损害。此前研究结果表明，乳酸能增强免疫细胞的抗癌活性，由于乳酸似乎会发挥相反的作用，因此未来的治疗性策略或许会重点关注将乳酸转化为乳酸盐从而促进免疫攻击。研究者还补充道，目前有研究人员正积极探索利用肿瘤酸度差异的其他潜在疗法，如研发能依据本文所揭示的较高酸度特性释放化疗药物的pH敏感载体，以便适时调整。总结而言，此项研究不仅揭示了癌细胞酸性极化的全新现象，更为科研人员指明了多个亟待深入探索的研究方向：如何解析癌细胞精确调控酸分泌极化的机制，这些细胞如何适应并耐受足以杀伤CD8+ T细胞的酸性条件，以及如何针对性地抑制酸分泌，从而助力T细胞更有效地清除癌细胞。这一系列前沿发现无疑将为人类抗击癌症的征程开启了崭新篇章。参考文献：Feng, Q., Bennett, Z., Grichuk, A. et al. Severely polarized extracellular acidity around tumour cells. Nat. Biomed. Eng (2024). doi：10.1038/s41551-024-01178-7本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

突破性疗法

2024-03-06

·BioSpace

OncoNano Medicine to Present Late-Breaking Poster at the American Association for Cancer Research (AACR) Annual Meeting 2024

SOUTHLAKE, Texas--(BUSINESS WIRE)-- OncoNano Medicine, Inc. today announced a late-breaking research poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place April 5-10, 2024 in San Diego, California. Presentation Overview: TITLE: Preclinical characterization of ONM-412, an ultra-pH sensitive nanoparticle encapsulated IL-12 fusion protein PRESENTER: Jason Miller, Ph.D., Associate Director, Research Pipeline Development, OncoNano Medicine DATE: April 10, 2024 TIME: 9:00 – 12:30 PM PT SECTION and PRESENTATION NUMBER: Poster Section 54, No. LB438 About OncoNano Medicine OncoNano Medicine is developing a new class of cancer therapeutics that utilize principles of molecular cooperativity in their design to exploit pH to diagnose and treat solid tumors with high specificity. Our polymeric micelles are designed to efficiently deliver oncology payloads to the tumor microenvironment for an enhanced therapeutic index. Our product candidates and interventions are designed to help patients across the continuum of cancer care and include solid tumor therapeutics, a platform of immuno-oncology therapeutics that activate and guide the body’s immune system to target cancer, and agents for real-time image guided surgery. OncoNano’s ON-BOARD™ platform is generating a robust oncology pipeline to support novel therapeutic development for patients with high unmet medical need. ONM-501, OncoNano’s first therapeutic program is a next generation dual-activating STING (STimulator of INterferon Genes) agonist currently in phase 1 studies. ONM-412, the highly potent pro-inflammatory cytokine, interleukin-12 (IL-12), encapsulated in the ON-BOARD™ polymeric micelle system is currently advancing in preclinical development. Additionally, the ON-BOARD™ platform has been used for pegsitacianine, a novel fluorescent nanoprobe that is being studied as a real-time surgical imaging agent for use in multiple cancer surgeries and is advancing towards a pivotal clinical trial to aid in tumor detection of peritoneal carcinomatosis. OncoNano is the top recipient of grants from CPRIT, which has supported the pegsitacianine and ONM-501 programs. Learn more about OncoNano’s platform and pipeline at .

临床1期AACR会议免疫疗法

100 项与 Pegsitacianine 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
原发性腹膜腺癌	临床2期	美国	OncoNano Medicine, Inc.	2021-11-30
腹膜继发性恶性肿瘤	临床2期	美国	OncoNano Medicine, Inc.	2021-11-30
乳腺癌	临床2期	美国	OncoNano Medicine, Inc.	2019-08-09
结直肠癌	临床2期	美国	OncoNano Medicine, Inc.	2019-08-09
非小细胞肺癌	临床2期	美国	OncoNano Medicine, Inc.	2019-08-09
卵巢癌	临床2期	美国	OncoNano Medicine, Inc.	2019-08-09
前列腺癌	临床2期	美国	OncoNano Medicine, Inc.	2019-08-09
头颈部鳞状细胞癌	临床2期	美国	OncoNano Medicine, Inc.	2019-08-09
尿路上皮癌	临床2期	美国	OncoNano Medicine, Inc.	2019-08-09

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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


NCT05576974 (ILLUMINATE, AHNS2025)	临床2期	原发灶不明的颈部鳞状细胞癌	15	Pegsitacianine (head and neck squamous cell carcinoma)	獵範網鹹餘窪範構積齋(糧範範簾鑰觸窪築蓋鹹) = two Grade 1 adverse events, including a transient elevation in ALT (alanine aminotransferase) and AST (aspartate aminotransferase) values 襯窪顧網齋夢製艱鹹鹹 (繭築齋鬱製醖憲築積簾 ) 更多	积极	2025-05-14
NCT05048082 (CTgov)	临床2期	肺癌	24	Tumor resection surgery+pegsitacianine	糧艱獵艱艱鬱鏇艱鑰餘 = 糧夢廠簾廠窪糧構顧壓憲積願夢願獵廠構襯鹽 (蓋齋鑰築廠構製觸衊襯, 製淵憲淵齋構鑰糧範積 ~ 顧壓範構衊壓鹹鬱醖壓) 更多	-	2024-11-08
NCT04950166 (CTgov)	临床2期	原发性腹膜腺癌 \| 腹膜继发性恶性肿瘤	51	pegsitacianine	願網顧鹹鑰構網顧範選 = 繭憲鏇膚糧餘網壓觸衊觸鬱網糧鏇願獵淵觸鹽 (醖廠簾選壓觸鬱選製範, 夢鏇獵鬱獵艱壓觸積廠 ~ 艱廠願艱積築壓齋糧鹹) 更多	-	2024-11-08
NCT04950166 (ASCO2023) 人工标引	临床2期	腹膜继发性恶性肿瘤	20	Pegsitacianine	艱鑰選壓築鏇築憲鑰獵(鑰膚觸壓夢簾鏇艱鏇鏇) = 蓋獵遞鬱築窪觸鬱積選積觸餘齋糧夢築顧願衊 (觸範餘願糧願齋簾壓鑰 ) 更多	积极	2023-05-31