177Lu-EBTATE / Molecular Targeting Tech, National Institutes of Health - LARVOL DELTA

177Lu-DOTA-EB-TATE in Adult Patients With Metastatic, Radioactive Iodine Non-Responsive Oncocytic (Hurthle-Cell) Thyroid Cancer (clinicaltrials.gov) - P1/2 | N=18 | Not yet recruiting | Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

New P1/2 trial • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Hurthle Cell Carcinoma

Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study. (PubMed, Acta Pharm Sin B) - "Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials."

Journal • P1 data • Preclinical • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR2

Preclinical safety and effectiveness of a long-acting somatostatin analogue [225Ac]Ac-EBTATE against small cell lung cancer and pancreatic neuroendocrine tumors. (PubMed, Eur J Nucl Med Mol Imaging) - "[225Ac]Ac-EBTATE is safe and effective against SCLC and pan-NET and therefore warrants clinical investigation."

Journal • Preclinical • Endocrine Cancer • Hepatology • Lung Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • SSTR2

Safety, Dosimetry, and Efficacy of an Optimized Long-acting Somatostatin Analog for Peptide Receptor Radionuclide Therapy in Metastatic Neuroendocrine Tumors: from Preclinical Testing to First-in-Humans Study (EANM 2024) - "However, A potential disadvantage of 177Lu-DOTATATE is its rapid blood clearance, resulting in relatively short tumor retention...No significant difference in whole-body mean effective dose was observed between 177Lu-LNC1010 and 177Lu-EB-TATE (0.23±0.06 vs. 0.23±0.08 mSv/MBq, P=1.00), however ,177Lu-LNC1010 exhibited 2.7-, 4.0-, and 3.0-fold higher radiation doses in the metastatic lymph nodes, liver, and other metastases than those of 177Lu-EB-TATE, respectively... The first-in-human trial with 177Lu-LNC1010 is well tolerated in patients with advanced NETs, with high radiation doses delivered to the tumor lesions. In addition, the dose-escalation study identified 3.3 GBq/cycle as the optimal therapeutic dose for future trials. Further investigations through multicenter, prospective, and randomized controlled trials are needed."

Metastases • P1 data • Preclinical • Endocrine Cancer • Hematological Disorders • Hepatology • Neuroendocrine Tumor • Oncology • Solid Tumor • Thrombocytopenia • SSTR2

Development of 177Lu‑LNC1010 for Peptide Receptor Radionuclide Therapy in Patients with Metastatic Neuroendocrine Tumors: from preclinical research to First-in-Human, Dose-escalation Study (SNMMI 2024) - "However, A potential disadvantage of 177Lu-DOTATATE is its rapid blood clearance, resulting in relatively short tumor retention...However, A potential disadvantage of 177Lu-DOTATATE is its rapid blood clearance, resulting in relatively short tumor retention...G3 thrombocytopenia was recorded in one patient in Group D (EB-TATE, 3... The first-in-human trial with 177Lu-LNC1010 is well tolerated in patients with advanced NETs, with high radiation doses delivered to the tumor lesions. Further investigations through multicenter, prospective, and randomized controlled trials are needed."

Metastases • P1 data • Preclinical • Endocrine Cancer • Hematological Disorders • Hepatology • Neuroendocrine Tumor • Oncology • Solid Tumor • Thrombocytopenia • SSTR2

Long acting [225Ac]Ac-EBTATE is highly efficacious against somatostatin receptor-2-positive neuroendocrine tumors (SNMMI 2024) - "[225Ac]Ac-EBTATE shows promise against SCLC and warrants clinical investigation."

Endocrine Cancer • Hematological Disorders • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • SSTR • SSTR2

MTTI Reports on ²²⁵Ac-EBTATE and ¹⁷⁷Lu-EBTATE Radiopharmaceuticals at 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting (Businesswire) - P=NA | N=NA | "Molecular Targeting Technologies, Inc. (MTTI), will update findings on both ¹⁷⁷Lu-EBTATE clinical and ²²5Ac-EBTATE preclinical work during the 2024 SNMMI meeting in Toronto June 8-11 (exhibition booth #1819)....'In our 3-year follow up on 30 patients* with metastatic neuroendocrine tumors (mNETs), ¹⁷⁷Lu-EBTATE demonstrated good safety, with no nephro- or hepatoxicity and 86% disease control rate using 60% less radioactivity than ¹⁷⁷Lu-DOTATATE'....'²²⁵Ac-EBTATE (2x 30 kBq administered 10 days apart) was effective against SCLC with 80% complete remissions and 100% survival. Treatment yielded a 2-fold greater tumor growth inhibition when compared with 225Ac-DOTATATE, at 60% less administered radioactivity."

Clinical data • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Efficacy of [67Cu]Cu-EB-TATE Theranostic Against Somatostatin Receptor Subtype-2-Positive Neuroendocrine Tumors. (PubMed, J Nucl Med) - "The antitumor efficacy of [67Cu]Cu-EB-TATE is comparable to that of [177Lu]Lu-EB-TATE, with [67Cu]Cu-EB-TATE being slightly more effective than [177Lu]Lu-EB-TATE for complete remission of small tumors. [67Cu]Cu-EB-TATE therefore warrants clinical development."

Journal • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR • SSTR2

177Lu-DOTA-EB-TATE in Adult Patients With Advanced, Well- Differentiated Neuroendocrine Tumors (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Molecular Targeting Technologies, Inc. | Trial completion date: Mar 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2024

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

Molecular Targeting Technologies, Inc. and Molecular Theranostics Center of Singapore Receive HSA Approval for Clinical Trial Authorization for EBTATE in Nasopharyngeal Cancer (Businesswire) - "Molecular Targeting Technologies, Inc. (MTTI), and its wholly owned subsidiary, Molecular Theranostic Center of Singapore (MTCS), announced the approval of a Clinical Trial Authorization (CTA) application by the Health Sciences Authority (HSA) of Singapore. The CTA enables a Phase IB/II, open-label study of the safety and efficacy of a 3-dose regimen of 177Lu-DOTA-EB-TATE (EBTATE) in patients with nasopharyngeal cancer (NPC) to be conducted at the National University Cancer Institute Singapore (NCIS) and the National University of Singapore (NUS)."

New P1/2 trial • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

MTTI Highlights Promising One-Year Follow-Up on EBTATE Treatment of Neuroendocrine Cancer Patients Without Amino Acid Infusion (Businesswire) - P1 | N=60 | NCT03478358 | "Molecular Targeting Technologies, Inc. (MTTI) announced promising results from a 1-year follow-up on EBTATE (2 cycles, 3.7 GBq/cycle) treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) without amino acid pretreatment. EBTATE’s safety, biodistribution, and dosimetry in a crossover randomized protocol in patients (N=10) with and without amino acids were published in Clinical Nuclear Medicine....'Our results showed that administration of EBTATE without amino acid infusion had acceptable kidney radiation absorbed dose and residence time. One month after EBTATE, there were no significant changes in creatinine, blood urea nitrogen (BUN), and glomerular filtration rate (GFR). None of the patients had nephrotoxicity of any grade'."

P1 data • Gastrointestinal Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

MTTI Announces Favorable Three-Year Follow-Up for EBTATE in Neuroendocrine Tumors (Businesswire) - P1 | N=60 | NCT03478358 | "Molecular Targeting Technologies, Inc. (MTTI) announced favorable findings of a 3-year follow-up of EBTATE (3 cycles, 3.7 GBq/cycle) against metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Results from this study were published in Theranostics....'Low occurrence of short and long-term toxicity proved EBTATE is safe (N=29). None of the patients developed leukemia or bone marrow disease during the 3-year follow-up. We observed low incidence of grade 3 hematoxicity (3.4% vs 15% of reported SOC) and no nephrotoxicity of any grade in long-term safety evaluation. Using EBTATE at lower radioactivity (37%) was as effective as SOC in disease control and achieved higher objective response based on RECIST criteria'."

P1 data • Gastrointestinal Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

Evaluation of Safety, Biodistribution, and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analog 177 Lu-DOTA-EB-TATE With and Without Amino Acid Infusion. (PubMed, Clin Nucl Med) - "177 Lu-DOTA-EB-TATE PRRT with and without amino acid infusion demonstrated a favorable safety profile in neuroendocrine tumor patients. Administration of 177 Lu-DOTA-EB-TATE without amino acid infusion has acceptable slightly increased kidney absorbed dose and residence time of the kidneys, and does not affect kidney function. Further investigation in a larger cohort and long-term follow-up are warranted."

Clinical • Journal • Endocrine Cancer • Hematological Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor • Thrombocytopenia

MTTI Obtains FDA Allowance of Investigational New Drug (IND) for Hürthle Cell Thyroid Cancer (Businesswire) - "Molecular Targeting Technologies, Inc...announced today the allowance of an Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA). It is now waiting for Institutional Review Board (IRB) approval. Once approved by IRB, it will enable a Phase I/II clinical study of the Safety, Dosimetry and Efficacy of EBTATE in adult patients with metastatic, radioactive iodine non-responsive Hürthle cell thyroid cancer."

IND • New P1/2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Hurthle Cell Carcinoma

Safety and efficacy of peptide receptor radionuclide therapy with Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors. (PubMed, Theranostics) - " Our results suggest that PRRT with approximately 3.7 GBq Lu-DOTA-EB-TATE has acceptable toxicity profile and is effective in treating metastatic NET with high disease control rate. In addition, Lu-DOTA-EB-TATE achieved a favorable survival outcome with encouraging PFS."

Journal • Endocrine Cancer • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Myelodysplastic Syndrome • Neuroendocrine Tumor • Oncology • Solid Tumor • Thrombocytopenia

Treatment Using 177Lu-DOTA-EB-TATE in Patients With Advanced Neuroendocrine Tumors (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Peking Union Medical College Hospital | Unknown status ➔ Recruiting | N=20 ➔ 60 | Trial completion date: Dec 2019 ➔ May 2023 | Trial primary completion date: Dec 2019 ➔ Dec 2022

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

177Lu-DOTA-EB-TATE in Untreated (Naïve) Adult Patients With Advanced, Well- Differentiated Neuroendocrine Tumors (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Molecular Targeting Technologies, Inc.

New P1 trial • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

"#MolecularTargetingTechnologies Features #EBTATE Advances at The #SNMMI22 Meeting In Vancouver, BC https://t.co/vLJRyLGchh" (@1stOncology)

MTTI and ITM Sign Clinical Supply Agreement for n.c.a. Lutetium-177 (Businesswire) - "Molecular Targeting Technologies Inc...announced the signing of a global clinical supply agreement that provides MTTI with ITM’s medical radioisotope no-carrier-added lutetium-177 (n.c.a. 177Lu / EndolucinBeta®) for the preclinical and clinical development as well as potential commercial production of MTTI’s radiopharmaceutical candidate n.c.a. 177Lu-EBTATE to treat a range of cancers...'This agreement underscores the potential of our n.c.a. lutetium-177 to provide therapeutic value to patients with hard-to-treat tumors and we are pleased to contribute to MTTI’s exciting program'."

Licensing / partnership • Oncology

MTTI partners with Evergreen to manufacture EvaThera platform of radiopharmaceuticals (PRNewswire) - "Molecular Targeting Technologies, Inc. (MTTI) and Evergreen Theragnostics, Inc...announced an agreement in which Evergreen will manufacture MTTI's EvaThera™ platform of radiopharmaceuticals....The EvaThera™ platform is a new generation of Evans blue-based molecules with strong affinity for albumin, which extends the blood half-life of the radiopharmaceutical, potentially leading to improved outcomes. MTTI's leading pipeline candidates are both Lu-177 based radiotherapeutics: EBTATE, targeting neuroendocrine and other SSTR2 expressing tumors, and EBRGD, targeting integrin expressing cancers like glioblastoma multiforme."

Licensing / partnership • Neuroendocrine Tumor • Oncology

Molecular Targeting Technologies, Inc. Says New Radiotherapeutic is Effective and Less Toxic for Neuroendocrine Tumor Patients (Businesswire) - "Molecular Targeting Technologies, Inc...announced...an article entitled 'Peptide Receptor Radionuclide Therapy (PRRT) of Late-Stage Neuroendocrine Tumor (NETs) Patients with Multiple Cycles of 177Lu-DOTA-EB-TATE' just published in the March issue of The Journal of Nuclear Medicine...Study participants were divided into three groups. Each group was given a different dose of EBTATE. All the groups tolerated the therapy well, with almost no side effects regardless of the dose. Ultimately, researchers found that an EBTATE dose of 1.89 GBq/cycle (GBq – gigabequerel measure of radioactivity) was the most effective for tumor control. They also noted that with careful patient selection and monitoring, a 3.97 GBq/cycle dose could achieve an even better response."

Clinical data • Neuroendocrine Tumor • Oncology

FDA Approves Investigational New Drug (IND) for Neuroendocrine Tumors from Molecular Targeting Technologies, Inc. (Businesswire) - "Molecular Targeting... announced today the approval of an Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA). It enables a Phase I clinical study of the Safety and Dosimetry of its lead product, EBTATE (177Lu-DOTA-EB-TATE), in patients with neuroendocrine tumors (NET)...The upcoming trial is an open-label, dose-escalation study planned for patients with neuroendocrine tumors (NET).'...MTTI expects to orchestrate multiple clinical trials in 2021."

IND • New trial • Neuroendocrine Tumor • Oncology