A Phase 1 Study to Evaluate the Dose, Safety and Tolerability of an Intraperitoneal α-emitting Radionuclide Therapy (Radspherin®) in Patients With Platinum Sensitive Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma With Peritoneal Carcinomatosis Following CRS

RAD-18-001 is a First-In-Man, Dose Escalation study conducted at 2 sites. The dose escalation will be performed based on a 3 + 3 design. Increasing dose levels starting at 1 MBq will be followed by 2, 4 and 7 MBq. If the highest dose level of 7 MBq is reached without Dose Limiting Toxicicities (which will stop the dose escalation), this will be the recommended dose for further exploration. Each subject will be followed until disease progression (in the abdominal cavity), or for 24 months after the administration of Radspherin® (whichever comes first).
In the expansion cohort the subject will receive the recommended dose. The expansion cohort will be conducted at 4 sites. Each subject will be followed until disease progression (in the abdominal cavity), or for 24 months after the administration of Radspherin® (whichever comes first).

开始日期2020-06-08

申办/合作机构

Oncoinvent AS

NCT03732781 / Active, not recruiting临床1/2期

A Phase 1/2a Study to Evaluate the Dose, Safety and Tolerability and Efficacy of an Intraperitoneal α-emitting Radionuclide Therapy (Radspherin®) in Subjects With Peritoneal Carcinomatosis From Colorectal Carcinoma Following Hyperthermic Intraperitoneal Chemotherapy

This is a phase 1/2a open label study to evaluate the dose, safety, tolerability and efficacy of an IP α-emitting radionuclide therapy (Radspherin®) in subjects with peritoneal carcinomatosis (PC) from colorectal carcinoma following complete CRS (cytoreduction score CC-0) and HIPEC.
The study consists of three different cohorts:
Dose escalation cohorts
Repeated injection cohorts
Expansion cohort

开始日期2020-05-27

申办/合作机构

Oncoinvent AS

100 项与 Radspherin 相关的临床结果

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100 项与 Radspherin 相关的转化医学

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100 项与 Radspherin 相关的专利（医药）

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项与 Radspherin 相关的文献（医药）

2023-01-01·Frontiers in medicine

First experience with ²²⁴Radium-labeled microparticles (Radspherin®) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study).

Article

作者: Goscinski, Mariusz Adam ; Larsen, Stein Gunnar ; Lundstrøm, Nadja ; Sørensen, Olaf ; Bruland, Øyvind Sverre ; Mariathasan, Anthony Burton ; Holtermann, Anne ; Revheim, Mona-Elisabeth ; Spasojevic, Milan ; Graf, Wilhelm ; Selboe, Silje

Background:

Peritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). With a median time to recurrence of 11-12 months, there is a need for novel therapies. Radspherin® consists of the α-emitting radionuclide radium-224 (²²⁴Ra), which has a half-life of 3.6 days and is adsorbed to a suspension of biodegradable calcium carbonate microparticles that are designed to give short-range radiation to the serosal peritoneal surface linings, killing free-floating and/or tumor cell clusters that remain after CRS-HIPEC.

Methods:

A first-in-human phase 1 study (EudraCT 2018-002803-33) was conducted at two specialized CRS-HIPEC centers. Radspherin® was administered intraperitoneally 2 days after CRS-HIPEC. Dose escalation at increasing activity dose levels of 1-2-4-7-MBq, a split-dose repeated injection, and expansion cohorts were used to evaluate the safety and tolerability of Radspherin®. The aim was to explore the recommended dose and biodistribution using gamma-camera imaging. The results from the planned safety interim analysis after the completion of the dose-limiting toxicity (DLT) period of 30 days are presented.

Results:

Twenty-three patients were enrolled: 14 in the dose escalation cohort, three in the repeated cohort, and six in the expansion cohort. Of the 23 enrolled patients, seven were men and 16 were women with a median age of 64 years (28-78). Twelve patients had synchronous PM stage IV and 11 patients had metachronous PM [primary stage II; (6) and stage III; (5)], with a disease-free interval of 15 months (3-30). The peritoneal cancer index was median 7 (3-19), operation time was 395 min (194-515), and hospital stay was 12 days (7-37). A total of 68 grade 2 adverse events were reported for 17 patients during the first 30 days; most were considered related to CRS and/or HIPEC. Only six of the TEAEs were evaluated as related to Radspherin®. One TEAE, anastomotic leakage, was reported as grade 3. Accordion ≥3 grade events occurred in a total of four of the 23 patients: reoperation due to anastomotic leaks (two) and drained abscesses (two). No DLT was documented at the 7 MBq dose level that was then defined as the recommended dose. The biodistribution of Radspherin® showed a relatively even peritoneal distribution.

Conclusion:

All dose levels of Radspherin® were well tolerated, and DLT was not reached. No deaths occurred, and no serious adverse events were considered related to Radspherin®.Clinical Trial Registration: Clinicaltrials.gov, NCT03732781.

2020-03-01·International journal of radiation oncology, biology, physics2区 · 医学

Initial Safety and Tumor Control Results From a “First-in-Human” Multicenter Prospective Trial Evaluating a Novel Alpha-Emitting Radionuclide for the Treatment of Locally Advanced Recurrent Squamous Cell Carcinomas of the Skin and Head and Neck

2区 · 医学

Article

作者: E. Rosenfeld ; R. Ben-Hur ; S.R. Bellia ; A. Mizrachi ; I. Kelson ; L. Deutsch ; A. Sarnelli ; L. Arazi ; Y. Keisari ; G. Feliciani ; A. Popovtzer

PURPOSE:

Our purpose was to report the feasibility and safety of diffusing alpha-emitter radiation therapy (DaRT), which entails the interstitial implantation of a novel alpha-emitting brachytherapy source, for the treatment of locally advanced and recurrent squamous cancers of the skin and head and neck.

METHODS AND MATERIALS:

This prospective first-in-human, multicenter clinical study evaluated 31 lesions in 28 patients. The primary objective was to determine the feasibility and safety of this approach, and the secondary objectives were to evaluate the initial tumor response and local progression-free survival. Eligibility criteria included all patients with biopsy-proven squamous cancers of the skin and head and neck with either primary tumors or recurrent/previously treated disease by either surgery or prior external beam radiation therapy; 13 of 31 lesions (42%) had received prior radiation therapy. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. Tumor response was assessed at 30 to 45 days at a follow-up visit using the Response Evaluation Criteria in Solid Tumors, version 1.1. Median follow-up time was 6.7 months.

RESULTS:

Acute toxicity included mostly local pain and erythema at the implantation site followed by swelling and mild skin ulceration. For pain and grade 2 skin ulcerations, 90% of patients had resolution within 3 to 5 weeks. Complete response to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 78.6%); 6 lesions (6/28, 21.4%) manifested a partial response (>30% tumor reduction). Among the 22 lesions with a complete response, 5 (22%) developed a subsequent local relapse at the site of DaRT implantation at a median time of 4.9 months (range, 2.43-5.52 months). The 1-year local progression-free survival probability at the implanted site was 44% overall (confidence interval [CI], 20.3%-64.3%) and 60% (95% CI, 28.61%-81.35%) for complete responders. Overall survival rates at 12 months post-DaRT implantation were 75% (95% CI, 46.14%-89.99%) among all patients and 93% (95% CI, 59.08%-98.96%) among complete responders.

CONCLUSIONS:

Alpha-emitter brachytherapy using DaRT achieved significant tumor responses without grade 3 or higher toxicities observed. Longer follow-up observations and larger studies are underway to validate these findings.

2018-12-01·EJNMMI research

Correlation of the absorbed dose to the blood and DNA damage in leukocytes after internal ex-vivo irradiation of blood samples with Ra-224

Article

作者: Schumann, Sarah ; Scherthan, Harry ; Lassmann, Michael ; Müller, Jessica ; Eberlein, Uta

BACKGROUND:

Irradiation with α-particles creates densely packed damage tracks along particle trajectories in exposed cells, including complex DNA damage and closely spaced double-strand breaks (DSBs) in hit nuclei. Here, we investigated the correlation of the absorbed dose to the blood and the number of α-induced DNA damage tracks elicited in human blood leukocytes after ex-vivo in-solution exposure with Ra-224. The aim was to compare the data to previously published data on Ra-223 and to investigate differences in DNA damage induction between the two radium isotopes.

RESULTS:

Blood samples from three healthy volunteers were exposed ex-vivo to six different concentrations of Ra-224 dichloride. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the Ra-224 decay chain, ranging from 0 to 127 mGy. γ-H2AX + 53BP1 DNA damage co-staining and analysis was performed on ethanol-fixed leukocytes isolated from the irradiated blood samples. For damage quantification, α-induced DNA damage tracks and small γ-H2AX + 53BP1 DSB foci were enumerated in the exposed leukocytes. This revealed a linear relationship between the frequency of α-induced γ-H2AX damage tracks and the absorbed dose to the blood, while the frequency of small γ-H2AX + 53BP1 DSB foci indicative of β-irradiation was similar to baseline values.

CONCLUSIONS:

Our data provide a first estimation of the DNA damage induced by Ra-224 in peripheral blood mononuclear cells. A comparison with our previously published Ra-223 data suggests that there is no difference in the induction of radiation-induced DNA damage between the two radium isotopes due to their similar decay properties.

项与 Radspherin 相关的新闻（医药）

2024-06-25

·Pharmaceutical Technology

Oncoinvent’s Radspherin has FDA fast-track status for ovarian cancer

A Phase IIb trial is assessing the safety and efficacy of the asset in patients with ovarian cancer-derived peritoneal metastases. Credit: Tattoboo/ Shutterstock. Oncoinvent has received fast-track designation from the US Food and Drug Administration (FDA) for its therapy, Radspherin, to treat peritoneal metastases from ovarian cancer. The process expedites the development and review of products targeting serious conditions with unmet medical needs, potentially enabling earlier patient access to new medicines. Fast-track status will offer Oncoinvent the advantage of more frequent interactions with the FDA throughout the clinical development of Radspherin. The designation makes it a candidate for accelerated approval and priority review. A lead candidate of the company, Radspherin is currently being evaluated in two active clinical studies for the treatment of peritoneal carcinomatosis resulting from both ovarian and colorectal cancer. See Also: Pharma M&A: The top high value deals in 2023 Medical packaging companies in pharmaceutical contract manufacturing An ongoing controlled, randomised Phase IIb clinical trial is assessing the safety and efficacy of Radspherin in patients with ovarian cancer-derived peritoneal metastases. The trial’s primary goal is to compare progression-free survival rates between patients receiving Radspherin post-surgical resection after pre-operative chemotherapy and those who receive the chemotherapy and surgery alone. Interim analysis from the Phase I/IIa safety study demonstrated promising results, with Radspherin offering a good tolerability profile. No dose-limiting toxicity was seen at the recommended 7MBq dose. Oncoinvent CEO Anders Månsson stated: “Fast track designation for Radspherin is a key milestone for Oncoinvent, particularly as we are on the verge of initiating a Phase IIb trial to evaluate Radspherin in peritoneal metastases from ovarian cancer, and later also in peritoneal metastases stemming from colorectal cancer patients. “We believe we are well positioned to execute the clinical development of Radspherin in our upcoming trial and look forward to advancing this innovative product candidate to benefit patients battling this type of cancer, for whom there are limited treatment options.”

临床2期快速通道临床结果

2024-06-24

·BioSpace

Oncoinvent Receives FDA Fast Track Designation for Radspherin® as Treatment for Peritoneal Carcinomatosis from Ovarian Cancer

Phase 2b trial of Radspherin® to treat ovarian cancer patients expected to initiate imminently OSLO, Norway--(BUSINESS WIRE)-- Oncoinvent AS, a clinical stage radiopharmaceutical company advancing alpha emitter therapy across a variety of peritoneal metastases, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to Radspherin® for the treatment of patients with peritoneal metastases from ovarian cancer. “Fast Track designation for Radspherin® is a key milestone for Oncoinvent, particularly as we are on the verge of initiating a Phase 2b trial to evaluate Radspherin® in peritoneal metastases from ovarian cancer, and later also in peritoneal metastases stemming from colorectal cancer patients,” said Anders Månsson, Chief Executive Officer of Oncoinvent. “Importantly, this designation reinforces the urgent need for safe and effective therapies for patients suffering from peritoneal metastases. These metastases have a particularly negative impact on life expectancy and effective treatment therefore has a significant chance of affecting overall survival in these patients. We believe we are well positioned to execute the clinical development of Radspherin® in our upcoming trial and look forward to advancing this innovative product candidate to benefit patients battling this type of cancer, for whom there are limited treatment options.” The randomized, controlled Phase 2b trial will assess the efficacy and safety of Radspherin® in patients with peritoneal metastases from ovarian cancer. The primary objective is to compare progression free survival (PFS) between patients who receive Radspherin® after complete surgical resection following pre-operative chemotherapy and patients who only undergo pre-operative chemotherapy and surgery. Positive data from the Phase 1/2a safety interim analysis demonstrated that Radspherin® was well tolerated with no dose-limiting toxicity observed with the administration of the recommended dose of 7MBq. Fast Track designation is a process that is designed to facilitate the development and expedite the review of therapies intended to treat serious conditions and address unmet medical needs to potentially bring important new medicines to patients earlier. Companies whose programs are granted Fast Track designation are eligible for more frequent interactions with the FDA during clinical development. Provided relevant criteria are met, programs with Fast Track designation are eligible for accelerated approval and priority review as well. About Oncoinvent Oncoinvent AS is a clinical stage company developing innovative radiopharmaceutical technology that delivers precise, alpha-emitting particles across solid cancers. By leveraging internal manufacturing and supply chain capabilities to enable a clinical supply of radioisotopes, the company is advancing a pipeline of novel products that use alpha particles, a higher Linear Energy Transfer (LET) form of radiation, that have been shown to eliminate cancer cells. Oncoinvent’s lead candidate, Radspherin®, is designed for treatment of metastatic cancers in body cavities, and its versatility allows it to be deployed for the treatment of a variety of cancer indications. Radspherin® is in two ongoing clinical studies to treat peritoneal carcinomatosis from both ovarian cancer and colorectal cancer. Forward-Looking Statements All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Oncoinvent’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Oncoinvent’s expectations as of the date of this press release, and Oncoinvent disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers.

快速通道临床2期

2024-05-15

·BioSpace

Oncoinvent to Present at Cantor Fitzgerald Frontiers in Radiopharma Virtual Summit

OSLO, Norway--(BUSINESS WIRE)-- Oncoinvent AS, a clinical stage company advancing alpha emitter therapy across a variety of solid cancers, today announced that members of management will participate in a virtual fireside chat at the Cantor Fitzgerald Frontiers in Radiopharma Virtual Summit on Monday, May 20, 2024 at 9:00 a.m. ET. About Oncoinvent Oncoinvent AS is a clinical stage company developing innovative radiopharmaceutical technology that delivers precise, alpha-emitting particles across solid cancers. By leveraging internal manufacturing and supply chain capabilities to enable a clinical supply of radioisotopes, the company is advancing a pipeline of novel products that use alpha particles, a higher Linear Energy Transfer (LET) form of radiation, that can potentially eradicate cancer cells. Oncoinvent’s lead candidate, Radspherin®, is designed for treatment of metastatic cancers in body cavities, and its versatility allows it to be deployed for the treatment of a variety of cancer indications. Radspherin® is in two ongoing clinical studies to treat peritoneal carcinomatosis from both ovarian cancer and colorectal cancer. Forward-Looking Statements All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Oncoinvent’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Oncoinvent’s expectations as of the date of this press release, and Oncoinvent disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers.

放射疗法临床研究

100 项与 Radspherin 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
结直肠癌	临床2期	挪威	Oncoinvent AS	2020-05-27
结直肠癌	临床2期	瑞典	Oncoinvent AS	2020-05-27
腹膜癌	临床2期	挪威	Oncoinvent AS	2020-05-27
腹膜癌	临床2期	瑞典	Oncoinvent AS	2020-05-27
卵巢癌	临床2期	挪威	Oncoinvent AS	-
铂敏感性原发性腹膜癌	临床1期	比利时	Oncoinvent AS	2020-06-08
铂敏感性原发性腹膜癌	临床1期	挪威	Oncoinvent AS	2020-06-08
铂敏感性原发性腹膜癌	临床1期	西班牙	Oncoinvent AS	2020-06-08
复发性卵巢癌	临床1期	比利时	Oncoinvent AS	2020-06-08
复发性卵巢癌	临床1期	挪威	Oncoinvent AS	2020-06-08

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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


NCT03732781 (ASCO2023) 人工标引	临床1/2期	肿瘤转移	23	Radspherin	顧顧鬱選築簾簾範顧餘(鬱願襯衊窪鑰顧衊鏇鏇) = 觸窪鹽夢積選簾蓋蓋獵範簾糧鏇餘顧艱壓遞艱 (襯憲築鹽鑰繭夢製糧願 ) 更多	积极	2023-05-31
2018-002803-33 (ASCO2022) 人工标引	临床1期	结直肠癌	23	radspherin	積選鑰築構鑰構願願選(築窪顧衊積願獵夢選鹹) = 觸淵獵構夢鏇淵獵廠淵淵夢夢觸襯簾艱製壓蓋 (壓窪壓構獵醖遞構蓋顧 ) 更多	积极	2022-06-02