AlphaMedix (ORM-2110) / RadioMedix, Orano, Sanofi - LARVOL DELTA

212Pb-DOTAMTATE: Impressive Efficacy in Treatment-Naive and Refractory Cohorts (Targeted Oncology) - "Dr Strosberg noted that the PRRT-refractory cohort, a heavily pretreated population, was smaller (n = 26) and had a shorter follow-up time of about 14.5 months, having been enrolled later in the study. Given heavy pretreatment, this group had a lower ORR (35%) compared with the PRRT-naive cohort, but the level of response activity was still considered strong for this population. The 18-month PFS rate ranged from approximately 75% to 80%."

Interview • Video

Dr Strosberg Highlights Positive 212Pb-DOTAMTATE Data in GEP-NETs (Targeted Oncology) - "Jonathan Strosberg, MD: The phase 2 ALPHAMEDIX-02 trial is exploring 212Pb-DOTAMTATE,a radioligand that targets somatostatin receptor-expressing neuroendocrine tumors, in patients with metastatic GEP-NETs. The study had two cohorts. One was comprised of patients who were PRRT-naive and the other was comprised of patients had received prior lutetium-based PRRT. The primary end points for the study were overall response rate by investigator analysis and adverse events. Secondary end points included progression-free survival (PFS) and overall survival (OS)."

Audio

Efficacy and safety of targeted alpha therapy 212Pb-DOTAMTATE in patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) previously treated with peptide receptor radionuclide therapy (PRRT): Results of a phase II study (ESMO 2025) - P2 | "Conclusions In pts with unresectable or metastatic SSTR+ GEP-NETs previously treated with PRRT, 212 Pb-DOTAMTATE (SAR447873) was associated with an clinically meaningful overall response rate of 30.8%. TEAEs were generally Gr1/2 and manageable."

Clinical • Metastases • P2 data • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Phase 2 Study of Targeted Alpha Therapy 212Pb-DOTAMTATE in Patients with Advanced Gastroenteropancreatic (GEP)-NETs Previously Treated with PRRT (NANETS 2025) - P2 | "CONCLUSIONS In patients with unresectable or metastatic SSTR+ GEP-NETs previously treated with PRRT,212Pb-DOTAMTATE (SAR447873) was associated with a clinically meaningful overall response rate of 30.8%. TEAEs were generally Grade1 or 2 and manageable."

Clinical • Metastases • P2 data • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • SSTR

212Pb-DOTAMTATE Shows Impressive Antitumor Activity in Previously Treated GEP-NETS (Targeted Oncology) - "Accordingly, Strosberg et al explored the next-generation SSTR-targeted RLT 212Pb-DOTAMTATE in this patient population. 212Pb-DOTAMTATE 'utilizes the high-energy and shorter-range alpha emission, which leads to highly effective dsDNA breakage and may result in more targeted oncologic effects,' explained Strosberg."

Media quote

Press Release: AlphaMedix (212Pb-DOTAMTATE) achieved all primary efficacy endpoints in phase 2 study, demonstrating clinically meaningful benefits in patients with gastroenteropancreatic neuroendocrine tumors (GlobeNewswire) - "Benefits in key secondary endpoints, including progression-free survival (PFS) and overall survival (OS), were also observed across both cohorts....The study is ongoing, and the full results will be presented at the 2025 European Society for Medical Oncology (ESMO) Congress."

P2 data • Neuroendocrine Tumor • Pancreatic Cancer

Activity standardization and determination of nuclear decay data of 212Pb at LNE-LNHB and first measurements in the SIR at BIPM. (PubMed, Appl Radiat Isot) - "In this paper, the activity standardization of 212Pb in equilibrium with its progeny was addressed by means of several measurement techniques at LNE-LNHB using a radioactive solution of 212Pb-DOTAMTATE supplied by Orano Med (France)...New γ-photon intensities based on γ-spectrometry were also measured. The present study on the metrological traceability of the radiopharmaceutical 212Pb is an important outcome in the framework of the European project EPM AlphaMet (Metrology for Emerging Targeted Alpha Therapies)."

Journal

ALPHAMEDIX01: Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET (clinicaltrials.gov) - P1 | N=33 | Terminated | Sponsor: Orano Med LLC | Recruiting ➔ Terminated; Terminated for non-safety reasons.

Trial termination • Endocrine Cancer • Neuroendocrine Tumor • Solid Tumor • SSTR

ALPHAMEDIX02: Targeted Alpha-emitter Therapy of PRRT Naïve and Previous PRRT Neuroendocrine Tumor Patients (clinicaltrials.gov) - P2 | N=69 | Active, not recruiting | Sponsor: Orano Med LLC | Trial completion date: Oct 2026 ➔ Oct 2028 | Trial primary completion date: Oct 2026 ➔ Oct 2028

Trial completion date • Trial primary completion date • Endocrine Cancer • Neuroendocrine Tumor • Solid Tumor • SSTR

Targeted Alpha Therapy with 212Pb-DOTAMTATE in subjects with advanced somatostatin receptor-expressing gastroenteropancreatic neuroendocrine tumors (NANETS 2024) - "BACKGROUND 212Pb-DOTAMTATE is a Targeted Alpha Therapy (TAT) in clinical development for subjects with SSTR+NETS. Three deaths were reported as fatal AEs: underlying progressive disease (N = 2) and multiorgan failure/sepsis (N=1) CONCLUSIONS In PRRT-naïve subjects with SSTR+ unresectable or metastatic GEP-NETs, treatment with ²¹²Pb-DOTAMTATE was well-tolerated, with a safety profile consistent with the underlying disease and expected toxicities of radioligand therapy, similar to 177Lu-DOTATATE. The 54.3% ORR in Cohort 1 (55.8% in pooled dataset) appears to be substantially higher than the ORR previously reported for 177Lu-DOTATATE in the pivotal NETTER-1 study (18% (10--25%))."

Clinical • Metastases • Endocrine Cancer • Hematological Disorders • Infectious Disease • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Septic Shock • Solid Tumor • SSTR

212Pb-DOTAMTATE Appears Safe, Effective in PRRT-Naïve Patients With SSTR+ GEP-NETs (Cancer Therapy Advisor) - "Dr Strosberg presented results with 212Pb-DOTAMTATE in 35 PRRT-naïve patients from the phase 2 ALPHAMEDIX-02 study (NCT05153772) and 8 PRRT-naïve patients from the phase 1 ALPHAMEDIX-01 study (NCT03466216). In the phase 2 study, 212Pb-DOTAMTATE (67.6 µCi/kg/cycle) was given every 8 weeks for a maximum of 4 cycles. Patients could also receive somatostatin analogue therapy for symptom control. In the phase 1 study, patients started with a single ascending dose of 212Pb-DOTAMTATE, and subsequent cohorts received an incremental 30% increase that continued until tumor response or dose-limiting toxicity. Once responses were observed, patients could receive additional doses at 8-week intervals."

P2 data

Press Release: Sanofi, RadioMedix, and Orano Med announce licensing agreement on next-generation radioligand medicine for rare cancers (GlobeNewswire) - "This collaboration between Sanofi, RadioMedix and Orano Med focuses specifically on the late-stage project, AlphaMedix (212Pb-DOTAMTATE), which currently is being evaluated for the treatment of adult patients with unresectable or metastatic, progressive somatostatin-receptor expressing neuroendocrine tumors (NETs), a rare cancer...AlphaMedix is currently completing phase 2 clinical development, and the data is being discussed with the FDA for potential regulatory filing and approval...Under the terms of the agreement, RadioMedix and Orano Med will receive an upfront payment of €100 million and up to €220 million in sales milestones and be eligible for tiered royalties."

Licensing / partnership • Trial status • Neuroendocrine Tumor • Oncology • Solid Tumor

June 2024: Dr. Aman Chauhan Discusses the Alpha PRRT with Pb-212 VMT Study (YouTube) - "Dr. Aman Chauhan Discusses the Alpha PRRT with Pb-212 VMT Study."

Video

Dr Strosberg on 212Pb-DOTAMTATE in Unresectable/Metastatic SSTR+ GEP-NETs (OncLive) - "Jonathan Strosberg, MD, discusses safety data for 212Pb-DOTAMTATE in metastatic somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors."

Video

Dr Strosberg on 212Pb-DOTAMTATE in Unresectable/Metastatic SSTR+ GEP-NETs (OncLive) - P2 | N=69 | ALPHAMEDIX02 (NCT05153772) | Sponsor: Radiomedix, Inc. | "Findings from cohort 1 presented at the 2024 ASCO Annual Meeting showed that evaluable patients not exposed to prior PRRT who received 212Pb-DOTAMTATE in the phase 1 ALPHAMEDIX01 trial (NCT03466216) or ALPHAMEDIX02 (n = 44) achieved an overall response rate (ORR) of 56.8% (95% CI, 42.2%-70.3%), which Strosberg notes is higher than ORRs typically observed in prior clinical trials investigating lutetium Lu 177 dotatate (Lutathera) in this patient population. In the phase 2 portion (n = 36), the ORR was 55.6% (95% CI, 39.6%-70.5%)....One AE that has stood out with 212Pb-DOTAMTATE is dysphagia, Strosberg continues."

P2 data • Gastrointestinal Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

Safety, tolerability and efficacy of 212 Pb-DOTAMTATE as a targeted alpha therapy for subjects with unresectable or metastatic somatostatin receptor-expressing gastroenteropancreatic neuroendocrine tumors (SSTR+ GEP-NETs): A phase 2 study. (ASCO 2024) - P2 | "Research Funding: No funding sources reported. In PRRT-naïve subjects with SSTR+ unresectable or metastatic GEP-NETs treatment with up to 4 cycles of ²¹²Pb-DOTAMTATE (67.6 μCi/kg/cycle) was well-tolerated, with a safety profile consistent with the underlying disease and expected toxicities of radioligand therapy, similar to 177 Lu-DOTATATE. The ORR of 47.2% in cohort 1 (50% in the pooled dataset) appears to be substantially higher than the ORR previously reported for 177 Lu-DOTATATE in the pivotal NETTER-1 study (ORR 18% (10–25%))."

Clinical • Metastases • P2 data • Carcinoid Syndrome • Endocrine Cancer • Hematological Disorders • Infectious Disease • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Septic Shock • Solid Tumor • SSTR

ALPHAMEDIX02: Targeted Alpha-emitter Therapy of PRRT Naïve and Previous PRRT Neuroendocrine Tumor Patients (clinicaltrials.gov) - P2 | N=69 | Active, not recruiting | Sponsor: Radiomedix, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

RadioMedix and Orano Med receive FDA Breakthrough Therapy Designation for AlphaMedix in gastroenteropancreatic neuroendocrine tumors First Targeted Alpha Therapy to receive a Breakthrough Therapy Designation (Businesswire) - "RadioMedix, Inc. and Orano Med...announced that the United States Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to AlphaMedix (212Pb-DOTAMTATE) for the treatment of adult patients with unresectable or metastatic, progressive somatostatin receptor expressing gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who are naïve to peptide receptor radionuclide therapy...The Breakthrough Therapy Designation is based on the results from phase 1 and the ongoing phase 2 clinical trials that assessed the safety and efficacy of AlphaMedix....In the phase 2 trial, the target response rate has already been achieved ahead of top-line data, expected in mid-2024."

Breakthrough therapy designation • P2 data • Neuroendocrine Tumor

ALPHAMEDIX02: Targeted Alpha-emitter Therapy of PRRT Naïve and Previous PRRT Neuroendocrine Tumor Patients (clinicaltrials.gov) - P2 | N=68 | Recruiting | Sponsor: Radiomedix, Inc. | N=34 ➔ 68 | Trial completion date: Dec 2023 ➔ Oct 2026 | Trial primary completion date: Dec 2022 ➔ Oct 2026

Enrollment change • Trial completion date • Trial primary completion date • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

Orano Med and Orbit Discovery Enter Collaboration to Discover Novel Targeted Radioligand Therapies for Cancer (Businesswire) - "Orano Med SAS...developing Lead-212 (212Pb) Targeted Alpha Therapy against cancer, and Orbit Discovery Ltd....announced that they have entered into a collaboration to discover specific Peptide Receptor Radionuclide Therapies against cancer cells and advance the development of novel radiopharmaceuticals. Under the terms of the agreement, Orbit will deploy its bead-based peptide display engine to discover peptide leads specific to targets related to specific tumours."

Licensing / partnership • Neuroendocrine Tumor

RadioMedix and Orano Med Complete Patient Enrolment in Phase II Trial of Targeted Alpha-Emitter AlphaMedix in Neuroendocrine Cancers (Businesswire) - "RadioMedix and Orano Med, two clinical stage radiopharmaceutical companies, today announced that the last patient has been dosed in the Phase II trial of the targeted alpha emitter therapy, 212Pb-DOTAMTATE (AlphaMedix™). This trial is being conducted to evaluate the safety and effectiveness of AlphaMedix™ in peptide receptor radionuclide therapy (PRRT) of naive patients with somatostatin receptor-expressing neuroendocrine tumors (NET), regardless of the location of the primary tumor. Top-line data from the trial is expected in mid-2024. Remarkably, based on data already collected, the objective response rate (ORR) endpoint has already been achieved and is more than twice as high as the current standard of care."

Enrollment closed • P2 data • Neuroendocrine Tumor • Oncology • Solid Tumor

Orano Med Starts Phase I Trial With Alpha Radioligand Therapy 212Pb-GRPR in Patients With Solid Tumors (Businesswire) - "Orano Med, a clinical stage radiopharmaceutical company, today announced that the first patient has been dosed in a Phase 1 trial of the alpha radioligand therapy with lead-212, 212Pb-GRPR, in patients with advanced solid tumors that express gastrin-releasing peptide receptor (GRPR). 212Pb-GRPR is the first targeted alpha therapy (TAT) targeting GRPR, a protein located on the surface of cells that is highly expressed in prostate cancer, lung cancer, breast cancer and other solid tumors."

Trial status • Oncology • Solid Tumor

Early data on 212Pb-DOTAMTATE (NANETS 2022) - No abstract available

Targeted alpha-emitter therapy with 212Pb-DOTAMTATE in neuroendocrine tumor subjects who progressed following prior 177Lu/90Y-PRRT. (ASCO 2022) - P1 | "Response to treatment was measured per RECIST 1.1 criteria and by 68Ga/64Cu-DOTATATE PET/CT. This is the first clinical trial of 212Pb-targeted alpha-emitter therapy in subjects with NETs who progressed following prior PRRT. The use of 212Pb-DOTAMTATE in the recurrent setting is highly effective with manageable toxicity and warrants further investigation."

Clinical • Alopecia • Anemia • Asthma • Endocrine Cancer • Fatigue • Gastrointestinal Disorder • Hematological Disorders • Immunology • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Septic Shock • Solid Tumor • SSTR

ALPHAMEDIX02: Targeted Alpha-emitter Therapy of PRRT Naive Neuroendocrine Tumor Patients (clinicaltrials.gov) - P2; N=34; Recruiting; Sponsor: Radiomedix, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • MRI • SSTR