Inclusion Criteria: 

Double-Blind Arms

• Male or female participants of ≥18 years of age who provide written informed consent.
• Participants with a clinical diagnosis and laboratory confirmation of tHI due to an islet or non-islet cell tumor (ICT [e.g. insulinoma], NICT), with associated hypoglycemia that is considered refractory to surgery (surgically unresectable, as indicated and appropriate) and to usual SOC medical anti-hypoglycemia therapies, per investigator judgement. Participants with NICT who otherwise meet eligibility criteria will be allowed to participate in the double-blind study arms after initial proof-of-concept in an open-label arm.
• Experiencing an average of ≥ 3 hypoglycemia events per week that meet Level 2 (blood glucose < 54 mg/dL [< 3 mmol/L] by SMBG) and/or Level 3 (events characterized by altered mental status and/or physical status requiring assistance for treatment of hypoglycemia, even if a blood glucose is not documented) criteria during the screening evaluation period.
• Must have an estimated minimum life expectancy of ≥ 3 months.
• ECOG performance status ≤ 2.
• Female participants of childbearing potential must not be pregnant or breast feeding, and willing to use effective contraceptive measures to prevent pregnancy for the duration of the study AND including for at least 3 months after receiving the last dose of study drug.
• Male participants with female partner of childbearing potential must be willing to use effective contraceptive measures to prevent pregnancy for the duration of the study AND including for at least 3 months after receiving the last dose of study drug.

Exclusion Criteria:

Double-Blind Arms

• Participants who require and are eligible and appropriate for tumor-directed therapies in lieu of trial enrollment for an investigational anti-hypoglycemia therapy, but who are not currently receiving and/or have not previously received tumor-directed therapy (including at least one course/trial of systemic tumor-directed therapy, as appropriate), as reviewed by and at the discretion of the investigator in conjunction with expert input from an oncologist and/or a multi-disciplinary oncology care team.
• Initiation of, or changes to tumor directed therapies (including surgery) within 4 weeks prior to screening and additionally within 8 weeks prior to initiation of study drug for systemic tumor directed therapies (e.g. Lutathera, radiation therapy, or chemotherapy), or expected initiation or changes to these therapies over the course of the pivotal treatment period.
• Initiation of, or significant changes to SOC medical (e.g. diazoxide, SSAs, continuous glucagon, mTOR-Inhibitors, etc.) or supplemental enteral treatments (e.g. continuous tube feeds) used for the chronic management of hypoglycemia within 4 weeks of screening (per investigator’s discretion) or expected changes to SOC medical therapies over the course of the pivotal treatment period.
• Any out-of-range laboratory value at screening (other than glucose) that is assessed as clinically significant by the investigator. Laboratory or radiographic abnormalities that are considered related to the underlying disease under study or associated therapies and do not pose additional safety risk for study participation per investigator and Medical Monitor may be allowed.
• A history of insulin or other anti-hyperglycemic agent for diabetes mellitus within 4 weeks of screening. 6. Average daily percent time with hyperglycemia ≥ 250 mg/dL (≥ 13.9 mmol/L) ≥ 5% of the monitored screening CGM time.
• Active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ (metastasis to other organs is not exclusionary).
• Seropositivity, indicative of active infection for human immunodeficiency virus, hepatitis B, or hepatitis C (excluding immunization patterns).
• Major surgery within 1 month before screening or anticipated during the study period (gastrostomy or other enteral catheter insertions, central or peripheral catheter insertion, or similar procedures are acceptable). 10. Symptomatic brain metastasis requiring active treatment (stable participants with radiation and/or steroid therapy may be allowed, per investigator).
• Participants with active, uncontrolled seizure disorder (stable participants with antiepileptic medication may be allowed, per investigator).
• Treatment with an investigational drug or device within 30 days or 5 half-lives of the investigational drug (whichever is longer), however, if the treating physician and Medical Monitor consider no significant risk of drug-drug interaction and potential benefit outweigh the risk then the participant may be allowed to participate. Participation in registries and purely diagnostic studies is allowed.
• Known allergy or sensitivity to ersodetug or any component of the drug.
• History of a significant cardio-vascular or cerebrovascular event within last six months (e.g. Class III or IV congestive heart failure, unstable angina, MI, stroke etc.).
• Any organ condition, concomitant disease (e.g., psychiatric illness, severe alcoholism, or drug abuse, cardiac, hepatic, or kidney disease), or other abnormality that itself, or the treatment of which, could interfere with the conduct of the study or that, in the opinion of the investigator and/or Sponsor’s Medical Monitor would pose an unacceptable risk to the participant in the study.

Inclusion Criteria:

Open-Label Arm (including initial/pilot NICT patients)

• Male or female participants of ≥18 years of age who provide written informed consent.
• Clinical diagnosis of neuroendocrine tumor (ICT or NICT) with biochemical evidence of tHI confirmed via laboratory assessment who have failed to achieve adequate control of hypoglycemia with usual SOC anti-hypoglycemic therapies, per investigator judgement.
• Hospitalized for management of uncontrolled hypoglycemia and requiring IV dextrose infusion and/or parenteral nutrition for ≥3 days; OR Initial/pilot OL NICT patients experiencing ≥3 Level 2 or Level 3 hypoglycemia events on an outpatient basis, during a minimum 7-day screening period. Non-hospitalized participants currently on IV glucose or parenteral nutrition may be enrolled in the OLA if considered appropriate by the investigator and Medical Monitor
• Female participants of childbearing potential must not be pregnant or breast feeding, and willing to use effective contraceptive measures to prevent pregnancy for the duration of the study AND including for at least 3 months after receiving the last dose of study drug.
• Male participants with female partner of childbearing potential must be willing to use effective contraceptive measures to prevent pregnancy for the duration of the study AND including for at least 3 months after receiving the last dose of study drug.

Exclusion Criteria:

Open-Label Arm

• Evidence of active infection including human immunodeficiency virus, hepatitis B, or hepatitis C (excluding immunization patterns).
• Treatment with an investigational drug or device within 30 days or 5 half-lives of the investigational drug (whichever is longer), however, if the treating physician and Medical Monitor consider no significant risk of drug-drug interaction and potential benefit outweighs the risk then the participant may be allowed to participate. Participation in registries and purely diagnostic studies is allowed.
• Any out-of-range laboratory value at screening (other than glucose) that is assessed as clinically significant by the investigator. Laboratory or radiographic abnormalities that are considered related to the underlying disease under study or associated therapies and do not pose additional safety risk for study participation per investigator and Medical Monitor may be allowed.
• Known allergy or sensitivity to ersodetug or any component of the drug.
• Any organ condition, concomitant disease (e.g., psychiatric illness, severe alcoholism, or drug abuse, cardiac, hepatic, or kidney disease), or other abnormality that itself, or the treatment of which in the opinion of the investigator and/or Sponsor’s Medical Monitor would pose an unacceptable risk to the participant in the study.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 9/3/2024. Questions regarding updates should be directed to the study team contact.