Zanzalintinib for Neuroendocrine Tumors

Recruiting at 1 trial location

Overseen By Nikolaos Trikalinos, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Oral anticoagulants, Platelet inhibitors

Disqualifiers: Brain metastases, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

32 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain oral anticoagulants and must stop them at least 3 days or 5 half-lives before starting the trial. If you are on somatostatin analogue therapy for well-differentiated high-grade tumors, you can continue it.

What data supports the effectiveness of the drug Zanzalintinib for neuroendocrine tumors?

Research on a similar drug, Surufatinib, which is also a tyrosine kinase inhibitor, has shown significant effectiveness in treating neuroendocrine tumors in clinical trials. This suggests that Zanzalintinib, if it works similarly, might also be effective for these tumors. ^{1 2 3 4 5}

How does the drug Zanzalintinib differ from other treatments for neuroendocrine tumors?

Zanzalintinib is a multitarget tyrosine kinase inhibitor, similar to other drugs like sunitinib, which are used to treat neuroendocrine tumors by targeting multiple pathways involved in tumor growth. This class of drugs is unique because it can simultaneously inhibit several key proteins that help tumors grow and spread, offering a broader approach compared to treatments that target a single pathway. ^{3 6 7 8 9}

What is the purpose of this trial?

The investigators hypothesize that zanzalintinib maintenance therapy after initial cytotoxic chemotherapy can prolong the progression-free survival (PFS) in patients with high-grade NENs.

Research Team

Nikolaos Trikalinos, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with high-grade neuroendocrine tumors, excluding lung and Merkel cell cancer. Participants must have stable disease or partial response after initial chemo, be able to consent, not pregnant, and agree to use contraception. They should have good organ function and performance status.

Inclusion Criteria

Measurable disease per RECIST 1.1

Ability to understand and willingness to sign an IRB approved written informed consent document

I am not pregnant and can have children.

Exclusion Criteria

Pregnant and/or breastfeeding

History of allergic reactions attributed to compounds of similar composition to zanzalintinib

Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms within 14 days before C1D1

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive initial cytotoxic chemotherapy

Varies

Maintenance Treatment

Participants receive zanzalintinib maintenance therapy in 28-day cycles

Up to 3 years

Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 4 years

Treatment Details

Interventions

• Zanzalintinib

Trial Overview The study tests if Zanzalintinib can extend the time patients live without their cancer getting worse after initial chemotherapy. Patients will receive Zanzalintinib as a maintenance therapy to see if it helps control tumor growth better than current standard care.

Participant Groups

Group I: Zanzalintinib Experimental Treatment 1 Intervention

Zanzalintinib will be taken by mouth once daily in 28-day cycles as maintenance therapy for up to 3 years.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Findings from Research

In the KEYNOTE-028 study, pembrolizumab showed antitumor activity in patients with well-differentiated or moderately-differentiated neuroendocrine tumors (NETs), with objective response rates of 12% for carcinoid tumors and 6.3% for pancreatic NETs after a median follow-up of 20 to 21 months.

The treatment was generally well-tolerated, with 68% to 69% of patients experiencing treatment-related adverse events, the most common being diarrhea and fatigue, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of programmed death-ligand 1-positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE-028 study. Mehnert, JM., Bergsland, E., O'Neil, BH., et al.[2021]

The review highlights the importance of somatostatin analogs and peptide receptor-targeted therapies in the treatment of neuroendocrine tumors, showcasing their efficacy in managing the disease.

It emphasizes the need for improved clinical trial designs and the development of biomarkers to better assess treatment outcomes and guide future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accomplishments in 2008 in the management of gastrointestinal neuroendocrine tumors. Kulke, MH., Scherübl, H.[2021]

Surufatinib, a tyrosine kinase inhibitor, is well-absorbed in both rats and humans, with a median time to peak concentration of 4 hours after oral dosing, and a significantly longer half-life in humans (23.3 hours) compared to rats (3.12-6.48 hours).

The primary route of elimination for surufatinib in both species is fecal excretion, accounting for about 87% of the dose, indicating that the drug is largely eliminated unchanged, with no single metabolite making up more than 10% of the total radioactivity in circulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption, Metabolism and Excretion of Surufatinib in Rats and Humans. Li, K., Ma, S., Miao, L., et al.[2021]

In a study involving 242 patients with advanced neuroendocrine tumors treated with surufatinib, the presence of treatment-related adverse events (TRAEs) like hypertension, proteinuria, and hemorrhage in the first 4 weeks was linked to a longer progression-free survival (PFS) of 11.1 months compared to 9.2 months for those without these events.

The findings suggest that TRAEs could serve as potential biomarkers for predicting the efficacy of surufatinib treatment, indicating that patients experiencing these side effects may have better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events as predictive biomarkers of efficacy in patients with advanced neuroendocrine tumors treated with surufatinib: results from two phase III studies. Li, J., Cheng, Y., Bai, C., et al.[2022]

In a phase II study involving 109 patients with advanced neuroendocrine tumors, sunitinib demonstrated a 16.7% objective response rate in pancreatic endocrine tumor patients and 2.4% in carcinoid patients, with a significant proportion of patients experiencing stable disease.

The treatment resulted in a median time to tumor progression of 7.7 months for pancreatic neuroendocrine tumors and 10.2 months for carcinoid tumors, with one-year survival rates of approximately 81% for pancreatic and 83% for carcinoid patients, indicating potential efficacy and safety for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of sunitinib in patients with advanced neuroendocrine tumors. Kulke, MH., Lenz, HJ., Meropol, NJ., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of programmed death-ligand 1-positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE-028 study. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Accomplishments in 2008 in the management of gastrointestinal neuroendocrine tumors. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Absorption, Metabolism and Excretion of Surufatinib in Rats and Humans. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events as predictive biomarkers of efficacy in patients with advanced neuroendocrine tumors treated with surufatinib: results from two phase III studies. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

CT evaluation of response in advanced gastroenteropancreatic neuroendocrine tumors treated with long-acting-repeatable octreotide: what is the optimal size variation threshold? [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of the tyrosine kinase inhibitor imatinib on neuroendocrine tumor cell growth. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Targeted inhibition of the WEE1 kinase as a novel therapeutic strategy in neuroendocrine neoplasms. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Emerging multitarget tyrosine kinase inhibitors in the treatment of neuroendocrine neoplasms. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Activity of sunitinib in patients with advanced neuroendocrine tumors. [2022]