Selpercatinib for Medullary Thyroid Cancer

(LIBRETTO-531 Trial)

Recruiting at 268 trial locations

Overseen By There will be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Loxo Oncology, Inc.

Disqualifiers: CNS metastases, Cardiovascular disease, Active infection, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 39 months

291 Participants Needed

Trial Summary

What is the purpose of this trial?

The reason for this study is to see if the study drug selpercatinib is safe and more effective compared to a standard treatment in participants with rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety profile of Selpercatinib for Medullary Thyroid Cancer?

Selpercatinib has been shown to have a manageable safety profile, with some patients experiencing gastrointestinal issues and other side effects like high blood pressure and elevated liver enzymes. Most side effects can be managed by adjusting the dose, and only a few patients stopped treatment due to these effects. ^{1 2 3 4 5}

How is the drug Selpercatinib unique for treating medullary thyroid cancer?

Selpercatinib is unique because it is a highly selective RET inhibitor, specifically targeting the RET mutations found in medullary thyroid cancer, unlike standard treatments that are multikinase inhibitors and can cause more side effects like diarrhea. This selectivity makes it a promising option for patients with RET-mutant medullary thyroid cancer. ^{1 3 4 5 6}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for adults and some minors (12+ if allowed) with advanced, inoperable or metastatic Medullary Thyroid Cancer that has a specific RET gene change. They shouldn't have had kinase inhibitor treatment before. Participants need to show disease progression, be reasonably healthy overall, able to swallow capsules, and willing to use effective contraception.

Inclusion Criteria

My tumor sample is large enough for further genetic testing.

My cancer has a specific change in the RET gene.

My cancer has grown according to recent scans, not just in bones.

Exclusion Criteria

I am currently experiencing significant bleeding or at high risk for serious bleeding.

I don't have serious heart issues or recent heart attacks, and my ECG results are within safe limits.

I do not have any uncontrolled infections or serious ongoing illnesses.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Selpercatinib or physician's choice of Cabozantinib or Vandetanib

Up to 39 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Crossover

Participants on standard treatment may crossover to Selpercatinib upon disease progression

Treatment Details

Interventions

• Cabozantinib
• Selpercatinib
• Vandetanib

Trial Overview The study tests if Selpercatinib is safer and more effective than standard treatments (Cabozantinib or Vandetanib) for RET-mutant MTC. If the standard treatment fails, participants may switch to Selpercatinib. The goal is to compare outcomes between the new drug and existing options.

Participant Groups

Group I: Selpercatinib - Treatment A (TRT A) Experimental Treatment 1 Intervention

160 milligrams Selpercatinib administered orally (PO) twice daily (BID). Adolescent Dose: 92 milligrams per square meter (mg/m2) BID (not to exceed 160 mg BID).

Group II: Cabozantinib or Vandetanib - Treatment B (TRT B) Active Control 2 Interventions

140 mg Cabozantinib administered orally daily (QD) or 300 mg Vandetanib administered orally QD per physician choice. Cabozantinib Adolescent Dose: 40 mg/m2. Vandetanib Adolescent Dose: * 0.7 - \<0.9 - 100 mg every other day (QOD) * 0.9 - \<1.2 - 100 mg QD * 1.2 - \<1.6 - 7-day schedule 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - 200 mg - 100 mg * ≥1.6 - 200 QD

Selpercatinib is already approved in United States, European Union for the following indications:

Approved in United States as RETEVMO for:

• RET fusion-positive or RET mutant thyroid cancers
• non-small cell lung cancer
• advanced or metastatic medullary thyroid cancer
• advanced or metastatic thyroid cancer with RET gene fusion
• locally advanced or metastatic solid tumors with RET gene fusion

Approved in European Union as RETEVMO for:

• RET-driven non-small cell lung cancer
• medullary thyroid cancer
• thyroid cancer

Who Is Running the Clinical Trial?

Loxo Oncology, Inc.

Lead Sponsor

Trials

72

Recruited

11,600+

Jacob Van Naarden

Loxo Oncology, Inc.

Chief Executive Officer since 2019

A.B. in Molecular Biology from Princeton University

Dr. Jennifer Low

Loxo Oncology, Inc.

Chief Medical Officer since 2014

MD and PhD from Georgetown University; Undergraduate degree from California Institute of Technology

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Selpercatinib (RETEVMO™) is a targeted therapy that inhibits the RET receptor tyrosine kinase, specifically designed for cancers with RET alterations.

It received FDA approval based on the promising results from the phase I/II LIBRETTO-001 trial for treating RET fusion-positive non-small-cell lung cancer, RET fusion-positive thyroid cancer, and RET-mutant medullary thyroid cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib: First Approval. Markham, A.[2021]

Selpercatinib is an effective oral treatment for advanced RET fusion-positive non-small cell lung cancer (NSCLC), showing strong and lasting responses in both previously treated and treatment-naïve patients during a pivotal phase 1/2 clinical trial.

The drug has a manageable safety profile, with most adverse events being manageable through dose adjustments, and only a small number of patients discontinuing treatment due to side effects, which primarily included hypertension and elevated liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib: A Review in Advanced RET Fusion-Positive NSCLC. Nie, T., Syed, YY.[2023]

In a phase 3 trial with 291 patients, selpercatinib demonstrated significantly better progression-free survival compared to cabozantinib or vandetanib, with a hazard ratio of 0.28, indicating a 72% reduction in the risk of disease progression or death.

Selpercatinib also showed a higher overall response rate of 69.4% compared to 38.8% in the control group, and it resulted in fewer treatment-related adverse events leading to dose reductions or discontinuations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. Hadoux, J., Elisei, R., Brose, MS., et al.[2023]

Selpercatinib demonstrated a clinically meaningful objective response rate of 43.9% in patients with RET fusion-positive advanced solid tumors, indicating its efficacy in a diverse, tumor-agnostic population of 45 patients enrolled in the LIBRETTO-001 trial.

The safety profile of selpercatinib was consistent with previous studies, with common grade 3 or worse adverse events including hypertension and liver enzyme increases, but no treatment-related deaths were reported, highlighting its relative safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. Subbiah, V., Wolf, J., Konda, B., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Selpercatinib: First Approval. [2021]

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

Selpercatinib Treatment of RET-Mutated Thyroid Cancers Is Associated With Gastrointestinal Adverse Effects. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Selpercatinib: A Review in Advanced RET Fusion-Positive NSCLC. [2023]

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

Patient-Reported Outcomes with Selpercatinib Treatment Among Patients with RET-Mutant Medullary Thyroid Cancer in the Phase I/II LIBRETTO-001 Trial. [2022]

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

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. [2022]