A Phase 3 Study of Ersodetug in Patients With Tumor-Associated Hyperinsulinism

The objectives of this study are to evaluate the glycemic efficacy, safety, and tolerability of ersodetug for treatment of hypoglycemia in patients with Tumor-Associated Hyperinsulinism (tHI).

This study will include participants who are suffering from low blood sugar (hypoglycemia) related symptoms due to over-production (too much) of hormones (e.g. insulin or similar substances) by certain tumors that cannot be treated satisfactorily with available treatment.

The study is divided into 3 periods: Screening (up to 4 weeks), Treatment (8 weeks) and either Follow-up (4 weeks) or optional Open Label Extension (OLE) phase (up to 3 years).

Overall, the study will enroll about 48 participants. Participants will be assigned to the appropriate treatment group depending on the type of tumor and whether they are hospitalized or not. For those not hospitalized, participants will be assigned in random order to either receive ersodetug or placebo (substance that looks like the study drug but does not contain active study drug) for the 8-week treatment period. All patients will receive ersodetug in the optional OLE period. The study will be comprised of the following treatment groups:

* Not hospitalized (referred to as ambulatory) insulin secreting tumor participants who receive usual treatment/standard of care therapies (SOC) and 9 mg/kg of ersodetug
* Ambulatory insulin secreting tumor participants who receive SOC and placebo
* Hospitalized (receiving IV dextrose or TPN ≥3 days) insulin or IGF secreting tumor participants who receive SOC and 9 mg/kg of ersodetug
* Ambulatory IGF secreting tumor participants who receive SOC and 9 mg/kg of ersodetug Participants should continue to use pre-existing anti-hypoglycemic medications and anti-tumor therapies throughout the study.

Eligibility Criteria:
Double-Blind Arm: (Ambulatory ICT and Ambulatory NICT participants)

Inclusion Criteria:

* The eligibility criteria of all participants must be evaluated by a multidisciplinary team led by the PI which must include an oncologist
* Male or female participants of ≥18 years of age who provide written informed consent
* Participants with a clinical diagnosis and laboratory confirmation of ICT or NICT, with associated hypoglycemia that is considered refractory to surgery and to usual SOC anti-hypoglycemia therapies, per investigator judgement.
* Experiencing an average of ≥ 3 hypoglycemia events per week that meet Level 2 criteria and/or Level 3 criteria during the two weeks before randomization

Exclusion Criteria:

* Participants who have not previously received tumor-directed therapy (including at least one course/trial of systemic tumor-directed therapy, as appropriate) but are considered appropriate for tumor-directed therapies by the investigator and/or a multi-disciplinary oncology care team.
* Initiation of, or changes to tumor directed therapies within 8 weeks prior to initiation of study drug, or expected initiation or significant 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.

Open-Label Arm: (Hospitalized ICT and NICT participants)

Inclusion Criteria:

* The eligibility criteria of all participants must be evaluated by a multidisciplinary team led by the PI which must include an oncologist
* Male or female participants of ≥18 years of age who provide written informed consent.
* Clinical diagnosis of neuroendocrine tumor (NET) (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.
* Requiring IV glucose infusion and/or parenteral nutrition for ≥3 days for management of uncontrolled hypoglycemia

Exclusion Criteria:

* Evidence of active infection including human immunodeficiency virus, hepatitis B, or hepatitis C (excluding immunization patterns).
* Any out-of-range laboratory value at screening (other than glucose) that is assessed as clinically significant by the investigator.
* 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.