A Phase 2 Open Label Study to Evaluate the Safety and Effectiveness of 212Pb-DOTAMTATE in Subjects With Somatostatin Receptor Expressing Neuroendocrine Tumors

Multicenter Phase 2 study of 212Pb-DOTAMTATE enrolling adult subjects with positive somatostatin positive neuroendocrine tumors with either no prior history of peptide receptor radionuclide therapy (PRRT naive) or prior history of peptide receptor radionuclide therapy (Previous PRRT)

Start Date21 Dec 2021

Sponsor / Collaborator

RadioMedix, Inc.

[+1]

NCT03466216

/ Unknown statusPhase 1

A Phase 1, Non-Randomized, Open-Label, Dose Escalation, Single-Center Study to Determine the Safety, Bio-distribution, and Preliminary Effectiveness of AlphaMedix™ in Adult Subjects With SSRT(+) NETs.

AlphaMedix™ (²¹²Pb-DOTAMTATE) is a radiotherapeutic drug indicated in subjects with unresectable, metastatic somatostatin receptor (SSTR) positive neuroendocrine tumors (NETs). Because 212Pb is an in vivo generator of alpha particles, it is particularly suitable for SSTR therapy applications.
This drug addresses an unmet need in the field of peptide receptor radionuclide therapy (PRRT) for NETs. Substitution of an alpha emitter (²¹²Pb) for the beta emitters currently being used (i.e., 177Lu or 90Y) will provide significantly higher Linear Energy Transfer (LET) and a shorter path length. Higher LET particles should cause more tumor cell death. Shorter path length should result in less collateral damage of the normal tissue and therefore less side effects for subjects receiving the drug.

Start Date05 Feb 2018

Sponsor / Collaborator

RadioMedix, Inc.

[+1]

EUCTR2011-002912-10-DE

/ Not yet recruitingNot Applicable

EFFICACY AND SAFETY OF ORAL OCTREOLIN™ IN PATIENTS WITH ACROMEGALY WHO ARE CURRENTLY RECEIVING PARENTERAL SOMATOSTATIN ANALOGS

Start Date21 Dec 2011

Sponsor / Collaborator

Chiasma, Inc.

100 Clinical Results associated with 212Pb-AR-RMX

100 Translational Medicine associated with 212Pb-AR-RMX

100 Patents (Medical) associated with 212Pb-AR-RMX

Literatures (Medical) associated with 212Pb-AR-RMX

01 Sep 2022·JOURNAL OF NUCLEAR MEDICINEQ1 · MEDICINE

Targeted α-Emitter Therapy with ²¹²Pb-DOTAMTATE for the Treatment of Metastatic SSTR-Expressing Neuroendocrine Tumors: First-in-Humans Dose-Escalation Clinical Trial

Q1 · MEDICINE

Article

Author: Tworowska, Izabela ; Torgue, Julien ; Delpassand, Ebrahim S ; Núñez, Rodolfo ; Hurt, Jason ; Esfandiari, Rouzbeh ; Shafie, Afshin

Peptide receptor radiotherapy with somatostatin analogs has been successfully used for years as a treatment for somatostatin-overexpressing tumors. Treatment of neuroendocrine tumors (NETs) with the β-particle emitter ¹⁷⁷Lu-DOTATATE is currently considered the standard of care for subjects with gastroenteropancreatic NETs. Despite the success of ¹⁷⁷Lu-DOTATATE, there remains significant room for improvement in terms of both safety and efficacy. Targeted α-emitter therapy with isotopes such as ²¹²Pb has the potential to improve both. Here, we present the preliminary results of the phase 1 first-in-humans dose-escalation trial evaluating ²¹²Pb-DOTAMTATE (a bifunctional metal chelator [DOTAM] and the SSTR-targeting peptide [TATE]) in patients with somatostatin receptor-positive NETs. Methods: Twenty subjects with histologically confirmed NETs, prior positive somatostatin analog scans, and no prior history of ¹⁷⁷Lu/⁹⁰Y/¹¹¹In peptide receptor radiotherapy, with different primary sites of the disease, were enrolled. Treatment began with single ascending doses of ²¹²Pb-DOTAMTATE, with subsequent cohorts receiving an incremental 30% dose increase, which was continued until a tumor response or a dose-limiting toxicity was observed. This was followed by a multiple ascending dose regimen. The recommended phase 2 dose regimen consisted of 4 cycles of 2.50 MBq/kg (67.6 μCi/kg) of ²¹²Pb-DOTAMTATE administered at 8-wk intervals, intravenously. Results: Ten subjects received the highest dose, 2.50 MBq/kg/cycle (67.6 μCi/kg/cycle). Treatment was well tolerated, with the most common treatment-emergent adverse events being nausea, fatigue, and alopecia. No serious treatment-emergent adverse events were related to the study drug, and no subjects required treatment delay or a dose reduction. An objective radiologic response of 80% was observed for the first 10 subjects treated at the recommended phase 2 dose. Conclusion: Targeted α-therapy with ²¹²Pb-DOTAMTATE has been shown to be well tolerated. Preliminary efficacy results are highly promising. If these results are confirmed in a larger, multicenter clinical trial, ²¹²Pb-DOTAMTATE would provide a substantial benefit over currently Food and Drug Administration-approved therapies for patients with metastatic or inoperable SSTR-expressing NETs regardless of the grade and location of the primary tumor.

01 May 2019·MOLECULAR CANCER THERAPEUTICS

Preclinical Investigation of 212Pb-DOTAMTATE for Peptide Receptor Radionuclide Therapy in a Neuroendocrine Tumor Model

Article

Author: Tworowska, Izabela ; Torgue, Julien J. ; Stallons, Tania A. Rozgaja ; Saidi, Amal ; Delpassand, Ebrahim S.

Abstract:

Somatostatin analogues have been examined as a treatment for somatostatin receptor overexpressing tumors for years; specifically, octreotate (TATE) and octreotide (TOC). Several versions of these analogues coupled to beta or gamma nuclides are currently used as imaging agents, as treatments with peptide receptor radionuclide therapy (PRRT) for patients with neuroendocrine tumors or are being explored in preclinical and clinical settings. Our study describes the use of 212Pb-DOTAMTATE, the octreotate analogue, in combination with 212Pb, the parent of an alpha emitter. Preclinical studies demonstrated tumor targeting of 212Pb-DOTAMTATE of >20% ID/g up to 24 hours post drug injection. The addition of kidney protection agents, including l-lysine and l-arginine decreases drug accumulation in the kidneys and the addition of ascorbic acid to the chelation mixture reduces oxidation of the drug product. 212Pb-DOTAMTATE displays a favorable toxicity profile with single-dose injections of 20 μCi showing 100% survival and with nontoxic cumulative doses up to 45 μCi, when fractionated into three smaller doses of 15 μCi. In an initial efficacy study, a single 10 μCi injection of 212Pb-DOTAMTATE extended the mean survival 2.4-fold. Efficacy was enhanced by giving three treatment cycles of 212Pb-DOTAMTATE and reducing the time between injections to two weeks. Efficacy was optimized further by the addition of a chemo-sensitizing agent, 5-fluorouracil, given in combination with three cycles of 10 μCi 212Pb-DOTAMTATE. These conditions led to 79% of the animals being tumor free at the end of the 31-week study suggesting that 212Pb-DOTAMTATE alone or in combination with a chemotherapeutic may have positive clinical implications.

01 Feb 2005·Annales d'endocrinologie

Article

Author: Schlienger, J-L

News (Medical) associated with 212Pb-AR-RMX

06 Mar 2025

·firstwordpharma.com

ITM fleshes out data for Phase III radiopharma success in neuroendocrine tumours

A radiopharmaceutical from ITM Isotope Technologies Munich reduced the risk of disease progression or death by 33% versus Novartis' targeted molecular therapy Afinitor (everolimus) in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). The outcome of the Phase III COMPETE study was first top-lined in January, with the announcement marking one of only a handful of wins for a radiopharmaceutical in a head-to-head trial. Detailed results were presented Thursday at the European Neuroendocrine Tumor Society (ENETS) annual meeting.The trial compared ITM-11 (177Lu-edotreotide) with Afinitor in 309 patients with inoperable, progressive Grade 1 or 2 somatostatin receptor (SSTR)-positive GEP-NETs. According to ITM, approximately 15% of people in each trial arm were treatment naïve, with the remaining 85% or so having received one prior therapy.Results showed that median progression-free survival (PFS) for ITM's therapeutic was 23.9 months, which was significantly and clinically better than the 14.1 months for Afinitor. In comparison, in the Phase III NETTER-2 trial, Novartis' peptide receptor radionuclide therapy Lutathera (lutetium Lu 177 dotatate) reduced the risk of disease progression or death by 72% as a first-line therapy for patients with SSTR-positive well-differentiated Grade 2/3 advanced GEP-NETs versus high-dose octreotide LAR alone, with median PFS in the two arms of 22.8 months and 8.5 months, respectively.ITM told FirstWord that the choice of Afinitor as a comparator in COMPETE was "backed by scientific evidence of efficacy and high clinical acceptance after market authorisation." The company suggested that this decision set "a higher standard for meeting the primary endpoint in more advanced grade tumours," adding that it hopes "physicians will recognise the higher threshold of our study design."FDA filing this year"These successful results validate our decision to design a pivotal Phase III trial directly comparing a targeted radiopharmaceutical against a targeted molecular therapy," CEO Andrew Carey said. Based on the findings, ITM plans to seek approval of ITM-11 in the US this year; however, the company told FirstWord that it is "currently prohibited" from filing in Europe until 2029 due to orphan drug designation on Lutathera.Top-line results also showed that interim median overall survival (OS) was 63.4 months for ITM-11. That was numerically higher than the 58.7 months seen with Afinitor, but not statistically significant at the current analysis. ITM noted that patients were allowed to start an alternative therapy after disease progression, "potentially confounding" the OS data."These data show unequivocal support for [ITM-11's] potential benefit in extending PFS," remarked study investigator Jaume Capdevila, adding that the radiopharmaceutical's "convenient dosing schedule and favourable safety results reinforce its potential as a compelling new treatment option."In COMPETE, patients were treated with ITM-11 every three months for up to four cycles, or with Afinitor daily for up to 30 months, or until disease progression. Meanwhile, ITM's therapy was well tolerated, with treatment-emergent adverse events occurring at a rate of 82.5%, compared with 97% for Afinitor. However, there was one Grade 2 event of myelodysplastic syndrome in the ITM-11 arm.Growing optionsNeuroendocrine tumours are one of the few cancers that have so far benefited from the approval of radiopharmaceuticals. Novartis currently markets Lutathera as a treatment for SSTR-positive GEP-NETs, while Sanofi also has skin in the game, having reached a deal last year to join forces with RadioMedix and Orano Med on the radioligand medicine AlphaMedix (212Pb-DOTAMTATE).Something that differentiates ITM from other players, however, is that it has worked in the radiopharma space for over 20 years and has manufacturing in-house. "Together, with our global isotopes manufacturing business, robust supply chain and experienced clinical and commercial team, we believe we are uniquely positioned as a standout leader in the fast-growing radiopharmaceutical industry," Carey said.ITM-11 — which combines the therapeutic β-emitting radioisotope lutetium-177 with the synthetic SSTR agonist edotreotide — is also being investigated in the Phase III COMPOSE trial in patients with well-differentiated, aggressive Grade 2 or 3 SSTR-positive GEP-NETs.

Phase 3Clinical ResultOligonucleotideOrphan Drug

06 Mar 2025

·www.pharmaceutical-technology.com

ITM targets US approval for radiopharmaceutical after Phase III readout

ITM-11 combines beta-emitting radioisotope lutetium-177 with somatostatin receptor (SSTR) agonist edotreotide. Credit: Love Employee via Getty Images. ITM Isotope Technologies Munich SE is gearing up to enter the US market with its radiopharmaceutical therapy, ITM-11 (177Lu-edotreotide), after promising Phase III trial results showed a significant advantage over Novartis’s targeted therapy Afinitor (everolimus) in treating gastroenteropancreatic neuroendocrine tumours (GEP-NETs). The company plans to seek regulatory approval later in 2025 following data from the Phase III COMPETE trial (NCT03049189). The full results were presented at the European Neuroendocrine Tumor Society (ENETS) annual meeting on 6 March in Krakow, Poland. An initial topline announcement on the trial meeting its primary endpoint was made in January 2025. The COMPETE trial evaluated ITM-11 in direct comparison with Afinitor in 309 patients with inoperable, progressive Grade 1 or 2 somatostatin receptor (SSTR)-positive GEP-NETs. Patients treated with ITM-11 had a median PFS of 23.9 months, compared to 14.1 months for Afinitor. While the interim median overall survival (OS) was numerically higher for ITM-11 at 63.4 months versus 58.7 months for Afinitor, the difference was not statistically significant, with ITM noting that OS data may have been affected by patients switching to alternative therapies after disease progression. The German company also reported new safety data. In the ITM-11 group, 82.5% of patients experienced treatment-emergent adverse events (TEAEs) compared to 97% of patients taking Afinitor. Radiopharmaceuticals have gained traction in oncology, particularly for neuroendocrine tumours. Novartis currently markets Lutathera (lutetium Lu 177 dotatate), an approved peptide receptor radionuclide therapy (PRRT) for SSTR-positive GEP-NETs. Sanofi has also entered the space, having partnered with RadioMedix and Qrane Med to develop AlRhaMedix (212Pb-DOTAMTATE), a radioligand therapy for neuroendocrine tumours. If approved, ITM-11 would compete with Lutathera. Novartis reported Lutathera sales of $724m in 2024, with forecasts projecting revenue growth to $910m by 2030, according to GlobalData’s Pharma Intelligence Center. GlobalData is the parent company of Pharmaceutical Technology. The rising interest in radiopharmaceuticals has led to increased investment from major pharmaceutical companies. Sanofi signed a $100m licensing agreement with RadioMedix and Qrane Med in September 2024, following Eli Lilly’s $1.1bn deal with Aktis Oncology in May 2024. AstraZeneca also expanded its radiopharmaceutical portfolio with a $2bn acquisition of Fusion Pharmaceuticals in June 2024. Despite growing demand, radiopharmaceutical supply chains have faced challenges. There have been shortages of the isotope actinium-225, used in the development of radiopharmaceuticals for treating metastatic castration-resistant prostate cancer (mCRPC), as companies like Novartis, Eli Lilly, and Johnson & Johnson pursue candidates utilising the isotope. ITM differentiates itself in the competitive landscape by maintaining in-house manufacturing capabilities. “Together, with our global isotopes manufacturing business, robust supply chain, and experienced clinical and commercial team, we believe we are uniquely positioned as a standout leader in the fast-growing radiopharmaceutical industry,” stated ITM’s CEO Andrew Cavey. In the announcement accompanying the data, Cavey said that the company plans to initiate another pivotal Phase III trial to further compare radiopharmaceuticals with targeted molecular therapies in Grade 1/2 GEP-NETs. “With this successful readout, 177Lu-edotreotide becomes the first drug candidate in ITM’s broad portfolio of early-to late-stage radiopharmaceuticals to deliver positive Phase III results and progress towards NDA submission and commercial launch preparations,” added Cavey.

Phase 3License out/inClinical ResultAcquisitionOligonucleotide

29 Oct 2024

·synapse.patsnap.com

Sanofi Joins Forces with RadioMedix and Orano Med to Pioneer Radioligand Therapies for Rare Cancers

On September 12th, Sanofi announced its entry into the nuclear medicine field through an exclusive licensing agreement with RadioMedix and Orano Med to jointly develop next-generation radioligand therapies (RLT) for rare cancers. According to the terms of the agreement, RadioMedix and Orano Med will receive a €100 million upfront payment and up to €220 million in sales milestone payments, along with eligibility for tiered royalties. This move marks Sanofi's official venture into the nuclear medicine sector, joining the ranks of global giants such as Novartis, Eli Lilly, and BMS. Focus on Nuclear MedicineBelow is an overview of the global clinical development pipeline for nuclear medicine. The radioligand therapy sector has attracted significant transaction activity in recent years, driven by promising market growth expectations. In 2023, venture capital transactions in this field increased by approximately 550%, surpassing $400 million. With more than 60 players already participating, this number is expected to rise as these therapies achieve greater clinical and commercial success. About AlphaMedix™RadioMedix is a US-based clinical-stage biotechnology company specializing in developing radiopharmaceuticals for PET imaging and targeted alpha therapy (TAT) to address unmet medical needs in cancer treatment. Orano Med, a French clinical-stage biotech company, focuses on developing lead-212 (212-Pb) radioligand therapies for cancer. The core project of this collaboration is AlphaMedix™ (212Pb-DOTAMTATE), an original targeted alpha therapy by Orano Med. It consists of a peptide complex targeting somatostatin receptors and is labeled with lead-212 (212Pb) as an in vivo alpha particle generator. AlphaMedix™ is currently being evaluated for treating adult patients with inoperable or metastatic, progressive neuroendocrine tumors (NETs) that express somatostatin receptors. The US FDA has granted AlphaMedix™ Breakthrough Therapy Designation for treating patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who have not undergone peptide receptor radionuclide therapy (PRRT). This designation is based on Phase I and II clinical trial results showing AlphaMedix's favorable tolerability and an overall response rate of 62.5%, assessed by RECIST 1.1 criteria. Neuroendocrine tumors (NETs) are a heterogeneous group of rare cancers originating from neuroendocrine cells. These cancers primarily occur in the gastrointestinal tract and pancreas but can also arise in other tissues, including the thymus, lung, and less commonly in the ovaries, heart, and prostate. Most NETs strongly express somatostatin receptors. In the United States, approximately 12,000 patients are diagnosed with neuroendocrine tumors annually, with an average five-year survival rate of 60% at the metastatic stage. Despite a rising global prevalence of NETs each year, it is considered a rare cancer, affecting an estimated 35 per 100,000 people. A key feature of nuclear medicine is its one-stop approach to diagnosis and treatment, as demonstrated by early 212-Pb development data. Dietmar Berger, Global Head of Development and Chief Medical Officer at Sanofi, said, "We are excited to develop pioneering projects in the rapidly evolving field of radioligand therapy for rare cancers. The early results of 212-Pb have already showcased its unique biophysical and clinical properties, reinforcing its potential as a transformative radioligand therapy for patients with challenging-to-treat rare cancers. This agreement underscores our commitment to exploring innovative technologies to address the needs of cancer patients." Understanding SanofiSanofi is a global leader in immunology, dedicated to reshaping and prioritizing its immunology pipeline through focused strategic decisions, leveraging its expertise to advance areas such as neuroinflammation and rare diseases. With a strong foundation in immunology, the company concentrates its expansion efforts on challenging-to-treat cancers like select hematological malignancies and solid tumors, and cancers with significant unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphoma, as well as gastrointestinal and lung cancers. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!

100 Deals associated with 212Pb-AR-RMX

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neuroendocrine Tumors	Phase 3	United States	Orano Med SAS	01 Dec 2021
Somatostatin Receptor-Positive Neuroendocrine Tumor	Phase 2	United States	Orano Med LLC	21 Dec 2021
Somatostatin Receptor-Positive Neuroendocrine Tumor	Phase 2	United States	RadioMedix, Inc.	21 Dec 2021

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05153772 (ALPHAMEDIX 02, ASCO2024)	Phase 2	Gastro-Enteropancreatic Neuroendocrine Tumor SSTR+	-	212Pb-DOTAMTATE	yzbfazwnfo(filajggrie) = bplxjbuzrb jkmxvjhibd (oauxsiyvov, 32.0 - 63.0)	Positive	24 May 2024
NCT05153772 (ALPHAMEDIX 02, ASCO2024)	Phase 2	Gastro-Enteropancreatic Neuroendocrine Tumor SSTR+	-	177Lu-DOTATATE	yzbfazwnfo(filajggrie) = oszvzdwqgs jkmxvjhibd (oauxsiyvov, 10 - 25)	Positive	24 May 2024
212Pb-DOTAMTATE (SNMMI2022)	Not Applicable	Neuroendocrine Tumors SSTR expressing	11	212Pb-DOTAMTATE at 67.6 µCi/kg/cycle	rkhxmzrwzw(xhvwqrkfbw) = vjjhbzvnfn ombfqhfjlz (atdueleume )	Positive	08 Aug 2022
NCT03466216 (ASCO2022) Manual	Phase 1	Neuroendocrine Tumors	10	212Pb-DOTAMTATE	qhdoqallxi(yjxunwhhwa) = oocugkmagm srmzzhtjwv (dlnxscixbt ) View more	Positive	02 Jun 2022
NCT03466216 (ASCO 12021 \| ASCO 22021) Manual	Phase 1	Neuroendocrine Tumors First line SSTR Expression	20	AlphaMedix	uyhbtiqexw(cfmaqpjyrg) = jshjerqval yfkfruessa (gkuykxxphv ) View more	Positive	20 May 2021
AlphaMedix (EANM2020)	Not Applicable	Neuroendocrine Tumors SSTR-	16	AlphaMedix 30.7 ÂµCi/kg	vslzyjeina(npzuuzcesv) = 7/16 (43%) ujjmentoog (qehxyglufs ) View more	Positive	18 Sep 2020
AlphaMedix (EANM2020)	Not Applicable	Neuroendocrine Tumors SSTR-	16	AlphaMedix 40.0 ÂµCi/kg		Positive	18 Sep 2020
FDA IND 135150 (AACR2020)	Not Applicable	Neuroendocrine Tumors	13	AlphaMedixTM	axiosvoniu(phtmgmiedu) = No clinically significant investigational drug-related hematological and renal toxicity was noted. kqtstfvmsa (qrkflnxrpx ) View more	Positive	15 Aug 2020
ESMO2019	Not Applicable	Apudoma	170	High doses analogs of somatostatin (SSA)	iooyjhajvu(taixnyblxy) = 12% rjmbkcyusa (hyuykszoyz ) View more	-	29 Sep 2019
ASCO2015	Not Applicable	Thymic Epithelial Tumor	-	Octreotide/lanreotide plus prednisone	nfobhiqnep(inpwncrhuk) = jlflioebkp gbmaxabewp (catrstpppy ) View more	Positive	20 May 2015

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