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

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

Radiomedix and Orano Med Announce the Initiation of the Phase II Multi-Center Clinical Trial of Alphamedix for Targeted Alpha-Emitter Therapy of Neuroendocrine Cancers (GlobeNewswire) - "RadioMedix and Orano Med are pleased to announce the initiation of the Phase II clinical trial of AlphaMedix™ with the treatment of the first patient on December 21st, 2021. This trial will evaluate the safety and effectiveness of 212Pb-DOTAMTATE (AlphaMedix™) in Peptide Receptor Radionuclide Therapy (PRRT) of naive patients with somatostatin receptor-expressing neuroendocrine tumors (NET)."

Trial status • Neuroendocrine Tumor • Oncology • Solid Tumor

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

Clinical • New P2 trial • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • MRI • SSTR

RADIOMEDIX AWARDED $2.0 M NCI SBIR DIRECT-TO-PHASE II GRANT TO DEVELOP DRUG FOR TARGETED ALPHA-EMITTER THERAPY (GlobeNewswire) - "RadioMedix...announced that it has been awarded a $2.0M Direct to Phase II Small Business Innovation Research (SBIR) grant from the National Cancer Institute at the US National Institutes of Health. The grant supports Phase I/II clinical development of innovative alpha-emitter labeled peptide, AlphaMedixTM, for therapy of somatostatin receptor-positive neuroendocrine tumors."

Financing • Neuroendocrine Tumor • Oncology

[VIRTUAL] First-in-human dose escalation of AlphaMedixTM for targeted alpha-emitter therapy of neuroendocrine tumors (AACR-I 2020) - "Dramatic decreases in tumor burden and a positive impact on quality of life were seen in all of the subjects who received three cycles of AlphaMedixTM at the highest dose tested. In addition, AlphaMedixTM was extremely well tolerated with only mild adverse events, most of which were attributable to the AA solution used for renal protection. This FIH study of AlphaMedixTM illustrates that PRRT with 212Pb is feasible, well-tolerated, and provides substantial reduction in tumor burden to patients with unresectable, metastatic SSTR expressing NETs"

P1 data • NFKBIA

[VIRTUAL] Phase I dose-escalation study of AlphaMedix for targeted-alpha-emitter therapy of PRRT-naive neuroendocrine patients. (ASCO 2021) - P1 | "This F-I-H clinical study of AlphaMedix shows that PRRT with 212Pb is feasible, well tolerated, and provides substantial reduction in tumor burden to patients with unresectable, metastatic SSTR-expressing NETs . Dramatic improvement in tumor burden and a positive impact on quality of life were seen in all of the PRRT naïve subjects who AlphaMedix at the highest dose tested."

Clinical • P1 data • Acute Kidney Injury • Alopecia • Back Pain • Diabetes • Fatigue • Musculoskeletal Pain • Nephrology • Oncology • Pain • Renal Disease • SSTR

ALPHAMEDIX01: Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET (clinicaltrials.gov) - P1; N=33; Recruiting; Sponsor: Radiomedix, Inc.; Completed ➔ Recruiting; Trial completion date: Jul 2021 ➔ Jul 2022; Trial primary completion date: Jul 2021 ➔ Jul 2022

Clinical • Enrollment open • Trial completion date • Trial primary completion date • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • MRI • SSTR

ALPHAMEDIX01: Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET (clinicaltrials.gov) - P1; N=33; Completed; Sponsor: Radiomedix, Inc.; Recruiting ➔ Completed; N=50 ➔ 33; Trial completion date: Nov 2021 ➔ Jul 2021

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

Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Radiomedix, Inc.; Trial primary completion date: Jul 2020 ➔ Jun 2021

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

[VIRTUAL] 212Pb-AlphaMedixTM Targeted Alpha Therapy (TAT): A potential breakthrough in treatment of metastatic SSTR expressing NET (NANETS 2020) - No abstract available