A Phase 1b, Open-label, Dose-escalation Clinical Study Evaluating the Safety of Camsirubicin With Prophylactic Pegfilgrastim in the Treatment of Advanced Soft Tissue Sarcomas

This is an Interventional Study in Advanced Soft Tissue Sarcomas (ASTS). It is a Phase 1b, open-label, dose-escalation clinical study evaluating the safety of camsirubicin with prophylactic pegfilgrastim in the treatment of advanced soft tissue sarcomas. The objective of the study is to evaluate the safety of camsirubicin with prophylactic pegfilgrastim in the treatment of ASTS and determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of camsirubicin with prophylactic pegfilgrastim. The primary endpoint is the MTD (RP2D).The secondary endpoints are: safety profile of camsirubicin with prophylactic pegfilgrastim, PFS, TTP, ORR, DoR, OS and PK. As exploratory endpoint, Quality of life will be measured by using the Functional Assessment of Cancer Therapy: General (FACT-G).

Start Date22 Sep 2021

Sponsor / Collaborator

Monopar Therapeutics, Inc.

NCT02267083 / CompletedPhase 2

Phase 2 Efficacy and Safety Study of Intravenous GPX-150, an Anthracycline Analog, in Patients With Soft Tissue Sarcoma

This study will assess the safety and efficacy of GPX-150 administered intravenously every 3 weeks in the treatment of patients with soft tissue sarcoma.

Start Date07 Jan 2015

Sponsor / Collaborator

Gem Pharmaceuticals LLC

NCT00710125 / CompletedPhase 1

Phase 1 Study and Dose Seeking Study of an Intravenous Formulation of the Anthracycline Analog GPX-150 in Patients With Solid Tumors

This is a Phase 1 safety and dose escalation study to define the maximum tolerated dose (MTD) and identify the dose limiting toxicities (DLT) following IV administration of GPX-150 once every 3 weeks. Escalating doses starting at the dose of 14 mg/m2 and increasing to the dose of 265 mg/m2 will be administered IV once every 3 weeks for up to 8 cycles of treatment. Patients who have previously received an anthracycline are limited to 4 cycles of treatment.

Start Date01 Jan 2008

Sponsor / Collaborator

Gem Pharmaceuticals LLC

100 Clinical Results associated with Camsirubicin

100 Translational Medicine associated with Camsirubicin

100 Patents (Medical) associated with Camsirubicin

Literatures (Medical) associated with Camsirubicin

01 Dec 2020·Cancer discoveryQ1 · MEDICINE

Pharmacologic Suppression of B7-H4 Glycosylation Restores Antitumor Immunity in Immune-Cold Breast Cancers

Q1 · MEDICINE

Article

Author: Hung, Mien-Chie ; Li, Hongchun ; Xue, Yifan ; Wan, Yong ; Kepp, Oliver ; Bahar, Ivet ; Song, Xinxin ; Zhou, Zhuan ; Kroemer, Guido ; Lu, Xinghua

Abstract:

Despite widespread utilization of immunotherapy, treating immune-cold tumors has proved to be a challenge. Here, we report that expression of the immune checkpoint molecule B7-H4 is prevalent among immune-cold triple-negative breast cancers (TNBC), where its expression inversely correlates with that of PD-L1. Glycosylation of B7-H4 interferes with its interaction/ubiquitination by AMFR, resulting in B7-H4 stabilization. B7-H4 expression inhibits doxorubicin-induced cell death through the suppression of eIF2α phosphorylation required for calreticulin exposure vis-à-vis the cancer cells. NGI-1, which inhibits B7-H4 glycosylation causing its ubiquitination and subsequent degradation, improves the immunogenic properties of cancer cells treated with doxorubicin, enhancing their phagocytosis by dendritic cells and their capacity to elicit CD8+ IFNγ-producing T-cell responses. In preclinical models of TNBC, a triple combination of NGI-1, camsirubicin (a noncardiotoxic doxorubicin analogue) and PD-L1 blockade was effective in reducing tumor growth. Collectively, our findings uncover a strategy for targeting the immunosuppressive molecule B7-H4.

Significance::

This work unravels the regulation of B7-H4 stability by ubiquitination and glycosylation, which affects tumor immunogenicity, particularly regarding immune-cold breast cancers. The inhibition of B7-H4 glycosylation can be favorably combined with immunogenic chemotherapy and PD-L1 blockade to achieve superior immuno-infiltration of cold tumors, as well as improved tumor growth control.See related commentary by Pearce and Läubli, p. 1789.This article is highlighted in the In This Issue feature, p. 1775

01 Jun 2019·Cancer medicine

A phase II clinical study of 13‐deoxy, 5‐iminodoxorubicin (GPX‐150) with metastatic and unresectable soft tissue sarcoma

Article

Author: Olson, Richard D. ; Talley, Todd T. ; Van Tine, Brian A. ; Klausner, Arthur ; Milhem, Mohammed M. ; Agulnik, Mark ; Walsh, Gerald M. ; Frank, Nicole E.

Abstract:

Background:

13‐Deoxy, 5‐iminodoxorubicin (GPX‐150) is a doxorubicin (DOX) analog synthesized to reduce the formation of reactive oxygen species and the cardiotoxic metabolite, doxorubiciniol, the two pathways that are linked to the irreversible, cumulative dose‐dependent cardiotoxicity of DOX. In a preclinical chronic models and a phase I clinical study of GPX‐150, no irreversible, cumulative dose‐dependent cardiotoxicity was demonstrated. Recent studies suggest that DOX cardiotoxicity may be mediated, at least in part, by the poisoning of topoisomerase IIβ.

Patients and Methods:

An open‐label, single‐arm phase II clinical study in metastatic and unresectable soft tissue sarcoma (STS) patients was initiated to further evaluate the efficacy and safety of GPX‐150, including cardiac function, specifically left ventricular ejection fraction (LVEF).

Results:

GPX‐150 was administered at 265 mg/m2 every 3 weeks for up to 16 doses with prophylactic G‐CSF until progression, death, or patient withdrawal from the study. GPX‐150 exhibited efficacy assessed as progression‐free survival (PFS) rates of 38% and 12% at 6 and 12 months and an overall survival rate of 74% and 45% at 6 and 12 months. GPX‐150–treated patients did not develop any evidence of irreversible, cumulative dose‐dependent chronic cardiotoxicity. Toxicities included grade 3 anemia, neutropenia, and one grade 4 leukopenia. Correlative analysis demonstrated that GPX‐150 was more selective than DOX for the inhibition of topoisomerase IIα over IIβ in vitro.

Conclusion:

These results suggest future studies are warranted to further evaluate the clinical efficacy of GPX‐150 in STS, perhaps at doses higher than 265 mg/m2.

01 Jun 2015·Investigational new drugsQ3 · MEDICINE

Phase I and pharmacokinetic study of the novel anthracycline derivative 5-imino-13-deoxydoxorubicin (GPX-150) in patients with advanced solid tumors

Q3 · MEDICINE

Article

Author: Sarah A. Holstein ; Raymond J. Hohl ; Gerald M. Walsh ; James C. Bigelow ; Richard D. Olson ; Robert E. Vestal

PURPOSE:

5-imino-13-deoxydoxorubicin (DIDOX; GPX-150) is a doxorubicin analog modified in two locations to prevent formation of cardiotoxic metabolites and reactive oxygen species. Preclinical studies have demonstrated anti-cancer activity without cardiotoxicity. A phase I study was performed in order to determine the maximum-tolerated dose (MTD) of GPX-150 in patients with metastatic solid tumors.

METHODS:

GPX-150 was administered as an intravenous infusion every 21 days for up to 8 cycles. An accelerated dose escalation was used for the first three treatment groups. The dosing groups were (A) 14 mg/m(2), (B) 28 mg/m(2), (C), 56 mg/m(2), (D) 84 mg/m(2), (E) 112 mg/m(2), (F) 150 mg/m(2), (G) 200 mg/m(2), and (H) 265 mg/m(2). Pharmacokinetic samples were drawn during the first 72 h of cycle 1.

RESULTS:

The MTD was considered to be reached at the highest dosing level of 265 mg/m(2) since dose reduction was required in 5 of 6 patients for neutropenia. The most frequent adverse events were neutropenia, anemia, fatigue, and nausea. No patients experienced cardiotoxicity while on the study. The best overall response was stable disease in four (20 %) patients. Pharmacokinetic analysis revealed an AUC of 8.0 (±2.6) μg · h/mL, a clearance of 607 (±210) mL/min/m(2) and a t1/2β of 13.8 (±4.6) hours.

CONCLUSIONS:

GPX-150 administered every 21 days has an acceptable side effect profile and no cardiotoxicity was observed. Further investigation is needed to determine the efficacy of GPX-150 in anthracycline-sensitive malignancies.

News (Medical) associated with Camsirubicin

09 May 2024

·www.fiercebiotech.com

Rallybio reins in preclinical R&D, while Monopar pivots to radiopharma to eke out cash

Monopar ended March with just shy of $9 million. The need to stretch strained bank balances has hit pipelines once again. Rallybio and Monopar are the latest biotechs to rethink their spending, respectively stopping preclinical investment and pivoting to radiopharmaceuticals to stretch limited resources. Rallybio shifted gears around 14 months ago, dropping its lead candidate for a second-generation asset in the same indication. The new lead candidate may be easier to deliver and manufacture but the switch delayed the biotech’s journey to a registrational trial. Since then, Rallybio has been shedding weight to free up financial fuel for its lead program. Having laid off 45% of its workforce in February, the biotech revealed in its first-quarter earnings results that it has now decided to stop pumping cash into its preclinical pipeline. Rallybio said it continues to believe in the promise of the prospects but will look for external sources of funding such as partnerships to take the candidates forward. The preclinical pipeline includes RLYB332, a long-acting version of RLYB331, an anti-Matriptase-2 antibody. Rallybio plans to present nonclinical data on a candidate it sees as a potentially best-in-class therapeutic for treating diseases of iron overload in the second half of the year. Over at Monopar, management has completed the pivot to radiopharma. The modality wasn’t on the biotech’s roadmap when it went public in 2019. But a preclinical anti-uPAR antibody that sat at the back of its pipeline at the time of the IPO later emerged as an enabler of a strategic shift. By conjugating the antibody to radioisotopes, Monopar has created a radiopharmaceutical program. With imaging and therapeutic opportunities on its plate, the biotech is dropping non-radiopharma assets including the phase 1b cancer candidate camsirubicin. Monopar ended March with just shy of $9 million, according to its own earnings release, a sum it forecasts will keep it going into at least next summer. Over that time, the biotech will continue to study its imaging asset in humans and move its first therapeutic radiopharmaceutical into the clinic. Monopar’s share price has rarely topped $1 over the past year, but the company used its radiopharma pivot to remind investors of the flurry of recent $1 billion-plus acquisitions by AstraZeneca, Bristol Myers Squibb, Eli Lilly and Novartis in the space. Elsewhere, RAPT Therapeutics is winding down two phase 2 trials recently placed on FDA clinical hold. The biotech reported in its first quarter earnings Thursday that it would close and unblind a phase 2a study testing zelnecirnon in patients with asthma and a phase 2b study in patients with atopic dermatitis. The hold was placed after a patient in the atopic dermatitis trial experienced liver failure, ultimately leading to organ replacement. The company first announced the holds in February, saying then that the cause was "characterized as potentially related to zelnecirnon." CEO Brian Wong, M.D., Ph.D., said in a release that the company still expects to have enough data to chart the drug’s path forward, even if they aren’t statistically significant. RAPT expects to finish its analysis of the data by the third quarter of the year, while continuing to investigate the adverse event. Editor's note: This story was updated to include details from RAPT Therapeutics' first quarter earnings.

Phase 2AcquisitionPhase 1IPOFinancial Statement

09 May 2024

·www.globenewswire.com

Monopar Therapeutics Reports First Quarter 2024 Financial Results and Strategic Focus on its Radiopharma Pipeline

Initiated MNPR-101-Zr First-in-Human Phase 1 Radiopharma Clinical Trial MNPR-101-RIT Phase 1 Clinical Trial Targeted for Launch as Early as Q4 2024 or Q1 2025 WILMETTE, Ill., May 09, 2024 (GLOBE NEWSWIRE) -- Monopar Therapeutics Inc. (Monopar or the Company) (Nasdaq: MNPR), a clinical-stage radiopharmaceutical company focused on developing innovative treatments for cancer patients, today announced first quarter 2024 financial results and summarized recent developments. Recent Developments The radiopharma space has had numerous positive recent developments and announcements, from acquisitions to clinical data to reimbursement rates to commercial demand. Since this past December alone, four significant acquisitions have been publicly announced or completed which have had upfront payments ranging from approximately $1 billion to over $4 billion (BMS/RayzeBio, AstraZeneca/Fusion Pharma, Eli Lilly/POINT BioPharma, and Novartis/ Mariana Oncology). Monopar has been generating promising preclinical data, and recently entered the clinic with its novel, proprietary MNPR-101 radiopharma program targeting the urokinase plasminogen activator receptor (uPAR). Based on these advances, Monopar has made the strategic decision to focus its resources on the assets and capabilities it has been building up in the radiopharma space. As such, the Company is winding down its non-radiopharma programs, including camsirubicin (and its Phase 1b clinical trial) as well as MNPR-202. The Company is targeting launching its second radiopharma clinical trial as early as the end of this year or the first quarter of 2025. MNPR-101 for Radiopharmaceutical Use – First-in-Human Study with MNPR-101-Zr is Now Active Received clearance and recently initiated a first-in-human Phase 1 imaging and dosimetry clinical trial with novel radiopharmaceutical MNPR-101-Zr in advanced cancer patients. Further information about the MNPR-101-Zr trial is available at www.ClinicalTrials.gov under study identifier NCT06337084. This study is being led by internationally recognized radiopharmaceutical physician Prof. Rodney Hicks, founder of the Melbourne Theranostic Innovation Centre (MTIC). Optimized imaging and therapeutic MNPR-101 radiopharma programs, significantly increasing tumor uptake while minimizing uptake in healthy tissue (link). This work led to in vivo efficacy studies demonstrating near complete elimination of the tumor after a single injection of the MNPR-101 radiopharmaceutical agent. Imaged the biodistribution of a therapeutic radioisotope bound to MNPR-101, and demonstrated highly preferential tumor uptake in the tumor consistent with what is seen with the Zr-89 imaging radioisotope (link). Filed a provisional patent application to protect the recent advancements and optimizations Monopar has achieved with its MNPR-101 radiopharma programs. Announced that Monopar’s abstract on MNPR-101-Zr radiopharma program was selected for presentation at the Society of Nuclear Medicine and Molecular Imaging’s Annual Meeting on June 8-11, 2024. Monopar is targeting initiating a Phase 1 clinical study in advanced cancers with its therapeutic radiopharmaceutical MNPR-101-RIT as soon as the end of this year or early next year. Results for the First Quarter Ended March 31, 2024, Compared to the First Quarter Ended March 31, 2023 Cash and Net Loss Cash, cash equivalents and short-term investments as of March 31, 2024, were $8.8 million. Monopar projects that its current funds will be sufficient to continue operations at least through June 30, 2025, to continue to conduct and conclude its first-in-human imaging and dosimetry clinical trial with MNPR-101-Zr, and to advance the preclinical MNPR-101-RIT therapeutic program into the clinic. Monopar will require additional funding to advance its preclinical and clinical programs beyond that, and anticipates seeking to raise additional capital within the next 12 months to fund its future operations. Net loss for the first quarter of 2024 was $1.6 million or $0.10 per share compared to net loss of $2.4 million or $0.19 per share for the first quarter of 2023. Research and Development (R&D) Expenses R&D expenses for the first quarter of 2024 were $966,000 compared to $1,653,000 for the first quarter of 2023. This decrease of $687,000 was primarily due to a decrease of $716,000 in Validive clinical trial-related expenses due to the closure of the trial in March 2023, partially offset by a net increase of $29,000 in other R&D expenses. General and Administrative (G&A) Expenses G&A expenses for the first quarter of 2024 were $757,000, compared to $872,000 for the first quarter of 2023. This represents a decrease of $115,000 primarily attributed to (1) a decrease in stock-based compensation to the non-employee directors of $70,000 as no equity awards were issued in the first quarter of 2024 compared to the first quarter of 2023, (2) a reduction of $62,000 in patent expenses related to the closure of the Validive trial, and (3) a reduction of stock-based compensation expenses to employees of $16,000 due to the full vesting of the 2020 grants in the fourth quarter of 2023, partially offset by a net increase in consulting, tax services and other G&A expenses of $33,000. About Monopar Therapeutics Monopar Therapeutics is a clinical-stage radiopharmaceutical company focused on developing innovative treatments for cancer patients, including Phase 1-stage MNPR-101-Zr for imaging advanced cancers and late preclinical-stage MNPR-101 radio-immuno-therapeutic (RIT) for the treatment of advanced cancers. For more information, and links to SEC filings that contain detailed financial information, visit: https://ir.monopartx.com/quarterly-reports. Forward-Looking StatementsStatements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Examples of these forward-looking statements include and are not limited to: that Monopar is targeting initiating a Phase 1 clinical study in advanced cancers with its therapeutic radiopharmaceutical MNPR-101-RIT as soon as the end of this year or early next year; and that current funds will be sufficient for Monopar to continue operations at least through June 30, 2025, to continue to conduct and conclude its first-in-human clinical trial with Monopar’s MNPR-101-Zr radiopharmaceutical program, and to advance the preclinical MNPR-101-RIT therapeutic program into the clinic. The forward-looking statements involve risks and uncertainties including, but not limited to: that we may expend available funds sooner than anticipated or require additional funding due to change in circumstances or unanticipated events; that future preclinical or clinical data will not be as promising as the data to date; not enrolling sufficient patients in the MNPR-101-Zr Phase 1 clinical trial or at all; that MNPR-101-Zr and/or MNPR-101 conjugated to a therapeutic radioisotope may cause unexpected serious adverse effects or fail to image or be effective against the cancer tumors in humans; and the significant general risks and uncertainties surrounding the research, development, regulatory approval, and commercialization of imaging agents and therapeutics. Actual results may differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in Monopar's filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Monopar undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Any forward-looking statements contained in this press release represent Monopar’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. CONTACT: Monopar Therapeutics Inc.Investor RelationsKim R. TsuchimotoChief Financial Officerkimtsu@monopartx.com Follow Monopar on social media for updates: Twitter: @MonoparTx LinkedIn: Monopar Therapeutics

Phase 1Financial StatementAcquisition

18 Apr 2024

·www.globenewswire.com

Monopar Announces Radiopharma Presentation Selected for Society of Nuclear Medicine and Molecular Imaging 2024 Annual Meeting

WILMETTE, Ill., April 18, 2024 (GLOBE NEWSWIRE) -- Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing innovative treatments for cancer patients, today announced that its abstract on the preclinical data for its radiopharmaceutical program MNPR-101-Zr (MNPR-101 conjugated to zirconium-89) submitted to the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2024 Annual Meeting has been selected for a presentation. SNMMI 2024, held in Toronto, Canada, is recognized as the premier educational, scientific, and research event in the radiopharma space. Meeting Details: Event: Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2024 Annual Meeting Date: June 8 – June 11, 2024 Location: Metro Toronto Convention Centre, Toronto, ON, Canada About Monopar Therapeutics Inc. Monopar Therapeutics is a clinical-stage biopharmaceutical company focused on developing innovative treatments for cancer patients. Monopar's pipeline consists of Phase 1-stage MNPR-101 for radiopharmaceutical use in various advanced cancers; Phase 1b-stage camsirubicin for the treatment of advanced soft tissue sarcoma; and an early-stage camsirubicin analog, MNPR-202. For more information, visit: www.monopartx.com and ir.monopartx.com/presentations. CONTACT: Monopar Therapeutics Inc.Investor RelationsKim R. TsuchimotoChief Financial Officerkimtsu@monopartx.com Follow Monopar on social media for updates: Twitter: @MonoparTx LinkedIn: Monopar Therapeutics

Phase 1

100 Deals associated with Camsirubicin

External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Soft Tissue Sarcoma	Phase 2	US	Gem Pharmaceuticals LLC	07 Jan 2015
Locally Advanced Soft Tissue Sarcoma	Phase 1	US	Monopar Therapeutics, Inc.	22 Sep 2021

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05043649 (Biospace \| NEWS) Manual	Phase 1	Soft Tissue Sarcoma	-	Camsirubicin (520 mg/m2)	zokhlohioo(ufhpxtemjj) = uegpdlehan dazmesgshu (pfkfkckvov ) View more	Positive	08 Aug 2023
NCT05043649 (Biospace \| NEWS) Manual	Phase 1	Soft Tissue Sarcoma	-	Camsirubicin	gugyqketxf(exdbgiuhxb) = ixydhaqflb hdczylswll (ouzxvtsfun ) View more	Positive	08 Aug 2023
NCT05043649 (MNPR-201-001, Corporate Publications) Manual	Phase 1	Soft Tissue Sarcoma	11	Camsirubicin	yjvbgjxjfa(xdfiasulos) = cpcylltavs ikoiakvqtx (luyknmojnm ) View more	Positive	16 Nov 2022
NCT02267083 (Pubmed) Manual	Phase 2	Soft Tissue Sarcoma	-	G-CSF+GPX-150	ehgvqfmshk(kqeanoaiby) = yhvdwosgah griibvhutf (szcnkcqyyb ) View more	Positive	01 Jun 2019
NCT02267083 (CTgov)	Phase 2	Soft Tissue Sarcoma	22	GPX-150 for Injection	lpdvenlurg(lzeksokbbl) = wxjfithmjl denlryiero (eaaxwmebbf, mwyskcnwoj - lkubnorrvc) View more	-	10 Jan 2018
NCT02267083 (ASCO2016)	Phase 2	Metastatic Soft Tissue Sarcoma	22	GPX-150	tfwhbvrlne(madpnhyflr) = 3 patients (14%) had grade 3 anemia ahylgkvbqv (ysapsubhvy ) View more	Positive	20 May 2016
NCT00710125 (ASCO2013)	Phase 1	Neoplasms	30	DIDOX	zftpiajdpi(rjfzbbqkap) = No cardiotoxicity was observed in any patient mvjjfpzkyo (xhxsyfxgin )	-	20 May 2013

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