Selpercatinib for Thyroid Cancer

(RAISE Trial)

Overseen By James Robinson

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital of Philadelphia

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors, QTc prolongers

Disqualifiers: Pregnancy, Cardiovascular disease, 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

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

13 Participants Needed

Trial Summary

What is the purpose of this trial?

Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer (DTC). The traditional first line treatment for patients with advanced DTC after surgical resection is radioactive iodine (RAI) therapy. However, less than a quarter of patients with lung metastases will achieve a complete response to RAI therapy, and this therapy carries the risk of pulmonary fibrosis and an increasingly recognized risk of secondary malignancies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take strong CYP3A4 inducers or inhibitors starting 14 days before the trial and during the study. Also, you should avoid medications that cause QTc prolongation.

What data supports the effectiveness of the drug Selpercatinib for thyroid cancer?

Selpercatinib has been shown to be effective in treating advanced RET fusion-positive thyroid cancer, as demonstrated in the phase I/II LIBRETTO-001 trial, which led to its approval by the US FDA. It has also shown promising results in other RET fusion-positive cancers, indicating its potential as a targeted therapy. ^{1 2 3 4 5}

Is selpercatinib safe for humans?

Selpercatinib has been shown to have an acceptable safety profile in clinical trials, with common side effects including high blood pressure, liver enzyme changes, and other manageable reactions. Serious warnings include potential liver damage, high blood pressure, heart rhythm changes, bleeding, allergic reactions, and risks to unborn babies. ^{2 3 6 7 8}

What makes the drug Selpercatinib unique for treating thyroid cancer?

Selpercatinib is unique because it is a highly selective RET kinase inhibitor specifically targeting RET alterations, which are genetic changes found in some thyroid cancers. This drug is designed to be more precise in its action compared to other treatments, potentially leading to better outcomes for patients with RET fusion-positive thyroid cancer. ^{1 2 3 4 5}

Research Team

Theodore W. Laetsch

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

This trial is for young patients aged 2-21 with advanced differentiated thyroid cancer post-surgery, who have multiple lung nodules or enlarging ones consistent with metastatic disease. They must have a RET gene alteration and good organ function, including blood counts and liver/kidney performance.

Inclusion Criteria

Agreement to use contraception during treatment

I am between 2 and 21 years old.

I can do most activities but need help with some.

Exclusion Criteria

I have not had any systemic treatment for thyroid cancer.

I am not pregnant or breastfeeding.

I am not taking any strong drugs that affect liver enzyme activity.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Selpercatinib Treatment

Participants receive selpercatinib monotherapy for 6 months at the FDA-approved dose

6 months

131I Therapy

Participants receive 131I therapy after 6 months of selpercatinib treatment

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• 131I Therapy
• Selpercatinib

Trial Overview The study tests Selpercatinib monotherapy before traditional radioactive iodine (RAI) therapy in pediatric thyroid cancer patients. It aims to see if pre-treatment with Selpercatinib can improve responses to RAI, which has limited effectiveness on its own.

Participant Groups

Group I: Experimental: Selpercatinib Monotherapy with 131I Therapy Experimental Treatment 2 Interventions

Patients will receive selpercatinib monotherapy for 6 months at the FDA-approved dose. Patients will receive 131I therapy after 6 months of selpercatinib. Selpercatinib will be continued for 5 days after RAI therapy and then patients will enter a wait and see period off treatment. Patients who experience disease progression at any point while on selpercatinib will proceed to 131I therapy and discontinue selpercatinib.

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?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

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 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]

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 II study involving 77 Chinese patients with advanced RET-altered thyroid cancer, selpercatinib demonstrated a high objective response rate (ORR) of 57.7% in the primary analysis set, indicating its efficacy in this population.

The treatment was generally well tolerated, with 59.7% of patients experiencing grade 3 or higher adverse events, leading to dose reductions in 32.5% of cases, suggesting that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of selpercatinib in Chinese patients with advanced RET-altered thyroid cancers: results from the phase II LIBRETTO-321 study. Zheng, X., Ji, Q., Sun, Y., et al.[2022]

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 received accelerated FDA approval for treating specific cancers associated with RET alterations, showing overall response rates (ORR) of 64% in RET fusion-positive non-small cell lung cancer and 100% in RET fusion-positive thyroid cancer, based on a multicenter clinical trial with significant duration of responses.

While effective, selpercatinib has safety warnings for potential side effects such as hepatotoxicity, hypertension, and embryo-fetal toxicity, highlighting the importance of monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Selpercatinib for the Treatment of Lung and Thyroid Cancers with RET Gene Mutations or Fusions. Bradford, D., Larkins, E., Mushti, SL., et al.[2022]

Selpercatinib, a novel specific RET inhibitor approved by the FDA in May 2020, targets RET alterations in lung and thyroid cancers, offering a more effective treatment option compared to multi-kinase inhibitors that often cause off-target toxicity.

The review discusses selpercatinib's mechanism of action and clinical data, highlighting its potential to improve outcomes for patients with RET-altered malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib for lung and thyroid cancers with RET gene mutations or fusions. Zheng, H., Chen, ZS., Li, J.[2021]

Selpercatinib (Retevmo) received accelerated FDA approval for treating adult patients with advanced solid tumors that have RET gene fusions, showing a 44% overall response rate in a study of 41 patients with various tumor types.

The treatment demonstrated a median duration of response of 24.5 months, indicating its potential long-term efficacy, while common side effects included edema, diarrhea, and fatigue, affecting over 25% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors. Duke, ES., Bradford, D., Marcovitz, M., et al.[2023]

References

1. 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]

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

Selpercatinib: First Approval. [2021]

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

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

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

Efficacy and safety of selpercatinib in Chinese patients with advanced RET-altered thyroid cancers: results from the phase II LIBRETTO-321 study. [2022]

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

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

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

FDA Approval Summary: Selpercatinib for the Treatment of Lung and Thyroid Cancers with RET Gene Mutations or Fusions. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Selpercatinib for lung and thyroid cancers with RET gene mutations or fusions. [2021]

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

FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors. [2023]