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.

Start Date17 Apr 2024

Sponsor / Collaborator

The University of Texas Southwestern Medical Center

[+1]

NCT05048082 / CompletedPhase 2

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.

Start Date13 Apr 2022

Sponsor / Collaborator

OncoNano Medicine, Inc.Startup

NCT04950166 / CompletedPhase 2

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

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.

Start Date30 Nov 2021

Sponsor / Collaborator

OncoNano Medicine, Inc.Startup

100 Clinical Results associated with Pegsitacianine

100 Translational Medicine associated with Pegsitacianine

100 Patents (Medical) associated with Pegsitacianine

Literatures (Medical) associated with Pegsitacianine

01 Aug 2024·Molecular Imaging and Biology

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

Article

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

PURPOSEIntraoperative 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.METHODSPatients 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.RESULTSTwenty 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.CONCLUSIONSPegsitacianine-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.

01 Jul 2024·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

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

BACKGROUNDFor 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 METHODSNCT04950166 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.RESULTSA 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.CONCLUSIONSPegsitacianine 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.

01 Jul 2024·Annals of Surgical Oncology

ASO Visual Abstract: Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using Pegsitacianine, a pH-Sensitive Imaging Agent—Final Results from a Phase 2 Study

Article

News (Medical) associated with Pegsitacianine

10 Apr 2024

·www.biospace.com

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 .

Phase 1AACRClinical ResultImmunotherapy

06 Mar 2024

·www.biospace.com

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 .

Phase 1AACRImmunotherapy

03 Nov 2023

·www.biospace.com

OncoNano Medicine Announces Positive Preclinical Data for ON-BOARD™ IL-12 Program at SITC 2023 Annual Meeting

SOUTHLAKE, Texas--(BUSINESS WIRE)-- OncoNano Medicine, Inc. today presented positive preclinical data describing the effective delivery of interleukin-12 (IL-12) with the ON-BOARD™ platform technology at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). The study findings show that encapsulation of a therapeutic IL-12 fusion protein (IL-12Fc) for tumor specific delivery and pH-dependent activation was achieved using the ON-BOARD™ polymeric micelle technology. The study also found that ON-BOARD™ significantly improved the tolerability of IL-12Fc, as compared to unencapsulated IL-12. The encapsulated IL-12Fc demonstrated potent anti-tumor efficacy and durable anti-tumor memory in the MC38 colorectal cancer model. ONM-412, the development product candidate with the IL-12 encapsulated in the ON-BOARD™ polymeric micelle system, is advancing through IND-enabling activities. “These findings underscore the potential application of the ON-BOARD™ polymeric micelle system for the delivery of IL-12 as an anti-tumor agent,” said Tian Zhao, PhD, Vice President of Research and Development at OncoNano. “We look forward to the continued development of ONM-412 and the ON-BOARD™ platform as a potential technology for the targeted delivery of therapeutics to benefit cancer patients.” The data presented demonstrated that: - ON-BOARD™ enables murine and human IL-12Fc encapsulation with favorable stability and pH-responsive IL-12 bioactivity in vitro in a HEK reporter assay and in primary cell IFNγ induction. Compared to a protease cleavable masked IL-12, the ON-BOARD™ formulation shows rapid and complete activation over a short period of time. - ON-BOARD™ encapsulated IL-12Fc exhibited potent anti-tumor efficacy and prolonged survival in MC38 tumor-bearing animals with long-term memory effect. - ON-BOARD™ formulation demonstrated effective IL-12 signaling in the tumor as evidenced by activation of CD8 T cells and NK cells; increased levels of IFNγ were seen in the tumor but not systemic circulation. - Reduced systemic exposure was observed with ON-BOARD™ encapsulated IL-12Fc with a significant improvement in the tolerability as evidenced by reduced body weight loss, normal plasma transaminase levels for liver function, reduced splenomegaly, and reduced systemic free IL-12 levels and IL-12 related cytokines when compared to unencapsulated IL-12Fc. Presentation Details Title: Encapsulation of IL-12 with an ultra pH-sensitive tumor delivery platform improves tolerability and promotes antitumor response in a preclinical model Presenter: Jason Miller, Ph.D., Associate Director, Research Pipeline Development, OncoNano Medicine Poster Number: 1147-B About OncoNano Medicine OncoNano Medicine is developing a new class of cancer products that utilize principles of molecular cooperativity in their design to exploit pH as a biomarker 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. ONM-501, OncoNano’s first therapeutic program, is a next generation dual-activating STING (STimulator of INterferon Genes) agonist that is advancing towards a first in human trial in the fourth quarter of 2023. OncoNano’s second therapeutic development program is ONM-412, the highly potent pro-inflammatory cytokine, interleukin-12 (IL-12), encapsulated in the ON-BOARD™ polymeric micelle system. 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. Pegsitacianine and ONM-501 have been supported by grants received from the Cancer Prevention Research Institute of Texas (CPRIT). Learn more at .

ImmunotherapyAACRClinical ResultClinical Study

100 Deals associated with Pegsitacianine

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Indication	Highest Phase	Country/Location	Organization	Date
Secondary malignant neoplasm of peritoneum	Phase 2	US	OncoNano Medicine, Inc.Startup	30 Nov 2021
Breast Cancer	Phase 2	US	OncoNano Medicine, Inc.Startup	09 Aug 2019
Colorectal Cancer	Phase 2	US	OncoNano Medicine, Inc.Startup	09 Aug 2019
Non-Small Cell Lung Cancer	Phase 2	US	OncoNano Medicine, Inc.Startup	09 Aug 2019
Ovarian Cancer	Phase 2	US	OncoNano Medicine, Inc.Startup	09 Aug 2019
Prostatic Cancer	Phase 2	US	OncoNano Medicine, Inc.Startup	09 Aug 2019
Squamous Cell Carcinoma of Head and Neck	Phase 2	US	OncoNano Medicine, Inc.Startup	09 Aug 2019
Transitional Cell Carcinoma	Phase 2	US	OncoNano Medicine, Inc.Startup	09 Aug 2019

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04950166 (ASCO2023) Manual	Phase 2	Secondary malignant neoplasm of peritoneum	20	Pegsitacianine	zazjrycgzo(uwasqoaxkv) = ywypgarwyv qaxfxqwryo (onklvrlhby ) View more	Positive	31 May 2023

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