SBIR-STTR Award

Direct to Phase II

A peptide receptor radionuclide therapy (PRRT) using beta-emitter-labeled somatostatin analogs has showedincrease in the progression-free-survival (PFS) of 177Lu-dotatate treated subjects, however the objectiveresponse rate of this group is rather low only 18% compare to control group. In addition, the number of completeresponses and partial responses seen in the daily clinical practice in Lutathera treated patients is also low. Thisis due to the heterogeneity of neuroendocrine tumors; advanced stage of disease at the time of diagnosis; andmore importantly tumor resistance to beta-emitter PRRT developed during the therapy. The targeted alpha-emitter therapy (TAT) of neuroendocrine tumors can overcome these limitations and our Phase I dose escalationstudies of 212Pb-DOTAMTATE (AlphaMedix) provide clinical evidence supporting this statement. Our dosePhase I study determined SAFE and HIGHLY EFFECTIVE DOSE of AlphaMedixTM in PRRT naïve patients withmetastatic neuroendocrine tumors regardless of the location of the primary tumor. All patients treated with thiseffective dose have shown the Objective Radiologic Response (ORR 83%) by RECIST criteria and almostcomplete response by NETSPOT PET/CT imaging. The main objective of proposed study is determination ofthe safety, PK, and efficacy of Alphamedix in PRRT refractory patients who failed and progressed after Lutathera.This will be accomplished during Phase I clinical study (amended IND 135150), followed by Phase II study(Protocol Number: RMX-Alpha-R020).OBJECTIVE 1. Phase I safety, efficacy and PK studies of the effective dose of Alphamedix in PRRT-refractorypatients regardless the primary origin the tumor. With successful completion of this objective, we will confirmthe efficacy and safety of recommended doses of Alphamedix, compile all modules for Phase II clinical studiesand request type B meeting and submit Phase II clinical protocol to IRB and FDA.OBJECTIVE 2. Phase II non-randomized, open-label, multi-center clinical studies of AlphaMedix in PRRTrefractory patients. With successful completion of the objective, we will determine the median Progression freesurvival (mPFS) and the Overall Survival (OS) of NETs patients, as well as their Time to Tumor Progression(TTP), and safety of the recommended doses of AlphaMedix.

Public Health Relevance Statement:
PROJECT NARRATIVE The proposal will assess the safety and efficacy of 212Pb-DOTAMTATE (AlphaMedix) in patients with SSTR(+) neuroendocrine tumors who progressed after Lutathera (177Lu-DOTATATE) treatment. Our Phase I dose escalation study determined the safe and highly effective dose of AlphaMedixTM in PRRT naïve patients with metastatic neuroendocrine tumors regardless of the location of the primary tumor. The hypothesis is that AlphaMedix treatment can induce significant increase in the objective response rate in PRRT refractory patients as it was seen in PRRT naïve patients. If successful, targeted alpha-emitter therapy using 212Pb-DOMTATATE can provide treatment options for neuroendocrine patients who cannot undergo surgery, chemotherapy or progressed after beta-emitter-PRRT.

Project Terms:
Affect ; Clinical Protocols ; Clinical Research ; Clinical Study ; Control Groups ; Diagnosis ; Disease ; Disorder ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Investigational Drugs ; Investigational New Drugs ; Grant ; Heterogeneity ; Investments ; Neoplasms ; neoplasia ; neoplastic growth ; Neuroblastoma ; Neurosecretory Systems ; Neuroendocrine ; Neuroendocrine System ; Octreotide ; Patients ; Production ; Radiology Specialty ; General Radiology ; Radiology ; Research ; Safety ; Somatostatin ; Cyclic Somatostatin ; Growth Hormone Inhibiting Factors ; Growth Hormone-Inhibiting Hormone ; SRIH ; SRIH-14 ; Somatostatin-14 ; Somatotropin Release Inhibiting Factors ; Somatotropin Release-Inhibiting Hormone ; growth hormone release inhibiting factor ; Testing ; Time ; X-Ray Computed Tomography ; CAT scan ; CT X Ray ; CT Xray ; CT imaging ; CT scan ; Computed Tomography ; Tomodensitometry ; X-Ray CAT Scan ; X-Ray Computerized Tomography ; Xray CAT scan ; Xray Computed Tomography ; Xray computerized tomography ; catscan ; computed axial tomography ; computer tomography ; computerized axial tomography ; computerized tomography ; Somatostatin Receptor ; SRIH Receptors ; Somatotropin Release Inhibiting Hormone Receptors ; Measures ; Organ ; tumor progression ; cancer progression ; neoplasm progression ; neoplastic progression ; Label ; improved ; Radionuclide therapy ; therapeutic radionuclide ; Clinical ; Refractory ; Phase ; Targeted Radiotherapy ; Peptide Receptor ; Neuroendocrine Tumors ; Neuroendocrine Neoplasm ; Progression-Free Survivals ; Funding ; Agonist ; SRIF2 receptor ; SSTR-2 ; somatostatin receptor type 2 ; somatostatin receptor 2 ; Double-Stranded DNA ; dsDNA ; ds-DNA ; Normal Tissue ; Normal tissue morphology ; Contracting Opportunities ; Contracts ; Malignant Cell ; cancer cell ; Neuroendocrine Therapy ; Protocol ; Protocols documentation ; Location ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; interest ; meetings ; physical property ; cohort ; dosimetry ; complete response ; In complete remission ; Primary Tumor ; Primary Neoplasm ; somatostatin analog ; Property ; response ; Address ; Length ; Dose ; Symptoms ; High Linear Energy Transfer Radiation ; High-LET Radiation ; Enrollment ; enroll ; Neuroendocrine Cell ; Patient-Focused Outcomes ; Patient outcome ; Patient-Centered Outcomes ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; partial response ; Development ; developmental ; PET/CT scan ; PET/CT ; open label ; open label study ; next generation ; clinical efficacy ; efficacy evaluation ; efficacy analysis ; efficacy assessment ; efficacy examination ; evaluate efficacy ; examine efficacy ; manufacturing facility ; innovation ; innovate ; innovative ; Resistance ; resistant ; chemotherapy ; therapy development ; develop therapy ; intervention development ; treatment development ; commercialization ; tumor ; overexpression ; overexpress ; effective therapy ; effective treatment ; Biological Markers ; bio-markers ; biologic marker ; biomarker ; clinical practice ; phase 1 study ; Phase I Study ; phase 2 study ; phase II study ; Institutional Review Boards ; IRB ; IRBs ; Drug Targeting ; treatment choice ; objective response rate ; liquid biopsy ; side effect ; Multi-site clinical study ; Multi-center clinical study ; Multicenter clinical study ; Multisite clinical study ; efficacy outcomes ;