What side effects are associated with this type of intervention?

The most common treatments for neuroendocrine tumor disease, particularly targeted radioligand therapies like Lutetium-177 labeled somatostatin analogues (177Lu-DOTATATE/TOC), have several known side effects. These include hematologic toxicities such as myelosuppression, which can lead to conditions like anemia, leukopenia, and thrombocytopenia. Patients may also experience nephrotoxicity, resulting in impaired kidney function. Other side effects can include nausea, vomiting, fatigue, and, in some cases, long-term risks such as myelodysplastic syndrome and acute myeloid leukemia, especially in those heavily pretreated with alkylating agents.

What prior FDA approvals exist?

The FDA has approved Lutetium Lu 177 dotatate (177Lu-DOTATATE) for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This targeted radioligand therapy has shown efficacy in controlling tumor growth and improving progression-free survival in patients with these types of tumors. Other systemic therapies for neuroendocrine tumors include everolimus, which has been approved for pancreatic neuroendocrine tumors, demonstrating significant improvement in progression-free survival.

What other types of research exist?

Promising novel alternatives to RYZ101 for NET patients in 2024 include 64Cu-DOTATATE, which offers diagnostic and logistical benefits, and 177Lu-DOTA-JR11, which has shown enhanced therapeutic efficacy in preclinical models. Additionally, tyrosine kinase inhibitors such as cabozantinib and vandetanib are also viable options for targeted therapy.

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Virus Therapy

RYZ101 for Neuroendocrine Tumors (ACTION-1 Trial)

Phase 3

Recruiting

Research Sponsored by RayzeBio, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Adequate renal function (CrCl ≥60 mL/min)

Histologically proven, Grade 1-2 well differentiated, inoperable, advanced GEP-NETs (Ki67 ≤20%)

Must not have

Any condition requiring systemic treatment with high-dose glucocorticoids within 14 days prior to first dose of study treatment and/or which cannot be stopped while on study. Inhaled or topical steroids are permitted

Significant cardiovascular disease, resistant hypertension, uncontrolled diabetes mellitus

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 80 months or until a total of 130 deaths have occurred, whichever occurs first

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests RYZ101, a new drug, in patients with advanced GEP-NETs that haven't responded to previous treatments. The drug aims to target specific receptors on the tumor cells to stop their growth.

Who is the study for?

This trial is for adults with advanced, inoperable GEP-NETs that express somatostatin receptors and have progressed after treatment with 177Lu-SSA therapy. Participants must have a life expectancy of at least 12 weeks, stable symptoms controlled by SSAs, adequate kidney and blood function, and agree to use effective contraception.

What is being tested?

The study tests RYZ101's safety and dosage compared to standard care therapies like Everolimus or Sunitinib in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). It has two parts: determining the safe dose of RYZ101 and comparing its effectiveness against other treatments.

What are the potential side effects?

Potential side effects include typical reactions related to cancer medications such as nausea, fatigue, changes in blood counts leading to increased infection risk or bleeding tendencies. Specific side effects of RYZ101 are not detailed but may be similar to those observed with comparable therapies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidneys are working well.

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My tumor is a low to intermediate grade and cannot be removed by surgery.

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I can take care of myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't taken high-dose steroids for my condition in the last 14 days.

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I do not have serious heart disease, uncontrollable high blood pressure, or diabetes.

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I have received PRRT treatment, but not with Lu-177 SSA.

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I have a history of liver cirrhosis.

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I am allergic to specific imaging agents or their components.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 80 months or until a total of 130 deaths have occurred, whichever occurs first

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 80 months or until a total of 130 deaths have occurred, whichever occurs first

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 80 months or until a total of 130 deaths have occurred, whichever occurs first for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1b: RP3D

Phase 3: PFS as determined by BICR

Secondary study objectives

Phase 1b: AUC

Phase 1b: Absorbed radiation doses of RYZ101 to critical organs and tumors

Phase 1b: Clearance

+12 more

Other study objectives

Electrocardiogram

Phase 3: AUC

Phase 3: Average Concentration

+7 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Phase 1b - RYZ101Experimental Treatment1 Intervention

Part 1 is an uncontrolled dose de-escalation study to confirm the safety and determine the RP3D of RYZ101 based on Bayesian optimal interval design.

Group II: Phase 3 - Standard of CareActive Control4 Interventions

Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.

Group III: Phase 3 - RYZ101Active Control1 Intervention

Actinium 225 radiolabeled somatostatin analog (SSA) for injection

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Targeted radioligand therapy, such as Lutetium-177 DOTATATE, works by binding to somatostatin receptors on the surface of neuroendocrine tumor cells. Once bound, the radioligand delivers localized radiation to the tumor cells, causing DNA damage and cell death while sparing surrounding healthy tissue. This targeted approach is crucial for NET patients as it offers a more precise treatment option with potentially fewer side effects compared to traditional chemotherapy. Other common treatments include somatostatin analogs, which inhibit hormone secretion and tumor growth, and molecularly targeted therapies like everolimus, which disrupts cancer cell proliferation by inhibiting the mTOR pathway. These therapies are important as they provide multiple avenues to control tumor growth and manage symptoms, improving the quality of life for NET patients.