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 Oct 2023·Molecular imaging and biology

A pH-Activatable Nanoprobe Labels Diverse Histologic Subtypes of Human Lung Cancer During Resection.

Article

Author: Bou-Samra, Patrick ; Desphande, Charuhas ; Rice, David C ; Kucharczuk, John C ; Kennedy, Gregory Thomas ; Chang, Austin ; Singhal, Sunil ; Azari, Feredun S ; Eruslanov, Evgeniy ; Delikatny, Edward J ; Chang, Ashley

BACKGROUND:

Intraoperative molecular imaging (IMI) uses tumor-targeted optical contrast agents to improve identification and clearance of cancer during surgery. Recently, pH-activatable contrast agents have been developed but none has been tested in lung cancer. Here, we report the successful clinical translation of pegsitacianine (ONM-100), a pH-activatable nanoprobe, for fluorescence-guided lung cancer resection.

METHODS:

We first characterized the pH setpoint for pegsitacianine fluorescence activation in vitro. We then optimized the specificity, dosing, and timing of pegsitacianine in murine flank xenograft models of lung adenocarcinoma and squamous cell carcinoma. Finally, we tested pegsitacianine in humans undergoing lung cancer surgery as part of an ongoing phase 2 trial.

RESULTS:

We found that the fluorescence activation of pegsitacianine occurred below physiologic pH in vitro. Using preclinical models of lung cancer, we found that the probe selectively labeled both adenocarcinoma and squamous cell carcinoma xenografts (mean tumor-to-background ratio [TBR] > 2.0 for all cell lines). In the human pilot study, we report cases in which pegsitacianine localized pulmonary adenocarcinoma and pulmonary squamous cell carcinoma (TBRs= 2.7 and 2.4) in real time to illustrate its successful clinical translation and potential to improve surgical management.

CONCLUSIONS:

This translational study demonstrates the feasibility of pegsitacianine as an IMI probe to label the two most common histologic subtypes of human lung cancer.

01 Dec 2021·Molecular imaging and biologyQ3 · MEDICINE

A Standardized Framework for Fluorescence-Guided Margin Assessment for Head and Neck Cancer Using a Tumor Acidosis Sensitive Optical Imaging Agent

Q3 · MEDICINE

Article

Author: Schepman, Kees-Pieter ; Witjes, Max Johannes Hendrikus ; Sumer, Baran Devrim ; Steinkamp, Pieter Jan ; Gao, Jinming ; de Visscher, Sebastiaan Antonius Hendrik Johannes ; van der Vegt, Bert ; van Dam, Gooitzen Michell ; Jayalakshmi, Yalia ; Doff, Jan Johannes ; Kelder, Wendy ; Voskuil, Floris Jan

Abstract:

Purpose:

Intra-operative management of the surgical margin in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) remains challenging as surgeons still have to rely on visual and tactile information. Fluorescence-guided surgery using tumor-specific imaging agents can assist in clinical decision-making. However, a standardized imaging methodology is lacking. In this study, we determined whether a standardized, specimen-driven, fluorescence imaging framework using ONM-100 could assist in clinical decision-making during surgery.

Procedures:

Thirteen patients with histologically proven HNSCC were included in this clinical study and received ONM-100 24 ± 8 h before surgery. Fluorescence images of the excised surgical specimen and of the surgical cavity were analyzed. A fluorescent lesion with a tumor-to-background ratio (TBR) > 1.5 was considered fluorescence-positive and correlated to standard of care (SOC) histopathology.

Results:

All six tumor-positive surgical margins were detected immediately after excision using fluorescence-guided intra-operative imaging. Postoperative analysis showed a median TBR (±IQR) of the fluorescent lesions on the resection margin of 3.36 ± 1.62. Three fluorescence-positive lesions in the surgical cavity were biopsied and showed occult carcinoma and severe dysplasia, and a false-positive fluorescence lesion.

Conclusion:

Our specimen-driven fluorescence framework using a novel, pH-activatable, fluorescent imaging agent could assist in reliable and real-time adequate clinical decision-making showing that a fluorescent lesion on the surgical specimen with a TBR of 1.5 is correlated to a tumor-positive resection margin. The binary mechanism of ONM-100 allows for a sharp tumor delineation in all patients, giving the surgeon a clinical tool for real-time margin assessment, with a high sensitivity.

Nature communicationsQ1 · CROSS-FIELD

Exploiting metabolic acidosis in solid cancers using a tumor-agnostic pH-activatable nanoprobe for fluorescence-guided surgery

Q1 · CROSS-FIELD

ArticleOA

Author: Schepman, K. P. ; Koller, M. ; Zhao, T. ; Been, L. B. ; Roodenburg, J. L. N. ; van Dam, G. M. ; Hall, K. ; Kruijff, S. ; Hartung, J. P. ; Witjes, M. J. H. ; van der Vegt, B. ; de Jongh, S. J. ; Doff, J. J. ; Jansen, L. ; van Ginkel, R. J. ; Kelder, W. ; van Loo, E. ; Voskuil, F. J. ; Steinkamp, P. J. ; Albaroodi, Y. ; Kruithof, I. ; Gao, J. ; Feng, Q. ; Jayalakshmi, Y. ; van Etten, B. ; de Visscher, S. A. H. J. ; Haveman, J. W. ; Shenoy, N. ; Hemmer, P. H. J. ; Havenga, K. ; Dijkstra, F. ; Sumer, B. D. ; Kats-Ugurlu, G.

Abstract:

Cancer cell metabolism leads to a uniquely acidic microenvironment in solid tumors, but exploiting the labile extracellular pH differences between cancer and normal tissues for clinical use has been challenging. Here we describe the clinical translation of ONM-100, a nanoparticle-based fluorescent imaging agent. This is comprised of an ultra-pH sensitive amphiphilic polymer, conjugated with indocyanine green, which rapidly and irreversibly dissociates to fluoresce in the acidic extracellular tumor microenvironment due to the mechanism of nanoscale macromolecular cooperativity. Primary outcomes were safety, pharmacokinetics and imaging feasilibity of ONM-100. Secondary outcomes were to determine a range of safe doses of ONM-100 for intra-operative imaging using commonly used fluorescence camera systems. In this study (Netherlands National Trial Register #7085), we report that ONM-100 was well tolerated, and four solid tumor types could be visualized both in- and ex vivo in thirty subjects. ONM-100 enables detection of tumor-positive resection margins in 9/9 subjects and four additional otherwise missed occult lesions. Consequently, this pH-activatable optical imaging agent may be clinically beneficial in differentiating previously unexploitable narrow physiologic differences.

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)	Phase 2	Secondary malignant neoplasm of peritoneum	40	Pegsitacianine	rfbfctrbwq(skztcwrrfj) = Treatment-related, non-anaphylactic infusion reactions occurred in 26% of patients and were transient, with a median duration of 9 minutes. gdrwcjnakl (mqmhuzvimk )	Positive	31 May 2023

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