Selpercatinib for Solid Tumors and Lymphomas

Recruiting at 182 trial locations

Overseen By Theodore W. Laetsch

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inducers/inhibitors, Anticancer agents

Disqualifiers: Pregnancy, 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

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 2 years

Trial Summary

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications before joining. You cannot be on other anti-cancer agents, investigational drugs, or medications that affect the CYP3A4 enzyme. If you are on corticosteroids, you need to be on a stable or decreasing dose for at least 7 days before enrolling.

Is selpercatinib safe for humans?

Selpercatinib has been shown to have an acceptable safety profile in clinical trials, with most side effects being manageable through dose adjustments. Common side effects include high blood pressure, elevated liver enzymes, swelling, diarrhea, fatigue, and dry mouth. ^{1 2 3 4 5}

What makes the drug Selpercatinib unique for treating solid tumors and lymphomas?

Selpercatinib is unique because it is a highly selective inhibitor that targets RET kinase, which is involved in certain genetic alterations found in some cancers. It is taken orally and has shown effectiveness in treating cancers with RET alterations, such as non-small cell lung cancer and thyroid cancer, offering a targeted approach compared to traditional chemotherapy. ^{1 2 5 6 7}

What is the purpose of this trial?

This phase II pediatric MATCH treatment trial studies how well selpercatinib works in treating patients with solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), lymphomas, or histiocytic disorders that have activating RET gene alterations. Selpercatinib may block the growth of cancer cells that have specific genetic changes in an important signaling pathway (called the RET pathway) and may reduce tumor size.

Research Team

Andrea T Franson

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for children and young adults up to 21 years old with advanced solid tumors, lymphomas, or histiocytic disorders that have specific RET gene changes. They must be in good physical condition with adequate organ function and not have been treated with selpercatinib before. Pregnant or breastfeeding individuals, those who've had major surgery recently, or are on certain medications affecting the immune system can't participate.

Inclusion Criteria

I have recovered from side effects of my previous cancer treatments.

I was assigned a treatment in the APEC1621SC study due to a specific mutation.

You have enough infection-fighting white blood cells in your body.

Exclusion Criteria

I do not have any infections that are currently uncontrolled.

I have been on a stable or decreasing dose of corticosteroids for at least 7 days.

I am not taking drugs that strongly affect liver enzyme CYP3A4.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selpercatinib orally twice daily on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Regular imaging and assessments throughout treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up for 30 days and periodically thereafter.

30 days initially, then periodic

Treatment Details

Interventions

• Selpercatinib

Trial Overview The trial is testing selpercatinib's effectiveness on patients whose cancer has spread and have alterations in the RET gene—a key driver of tumor growth. It involves imaging tests like CT scans, MRIs, PET scans, and X-rays to monitor response to treatment.

Participant Groups

Group I: Treatment (selpercatinib) Experimental Treatment 6 Interventions

Patients receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Children's Oncology Group

Collaborator

Trials

467

Recruited

241,000+

Findings from Research

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]

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]

In a study of 329 patients with RET fusion-positive NSCLC, 7% experienced hypersensitivity reactions to selpercatinib, with a higher incidence in patients previously treated with immune checkpoint inhibitors (ICIs) (77% of cases).

Hypersensitivity reactions to selpercatinib were manageable with supportive care, and many patients were able to continue treatment after dose modifications, indicating that while there is a risk, it is generally low and reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001. McCoach, CE., Rolfo, C., Drilon, A., et al.[2022]

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]

Selpercatinib showed a high objective response rate (ORR) of 84% in treatment-naive patients and 61% in those previously treated with platinum-based chemotherapy, indicating its efficacy in RET fusion-positive non-small-cell lung cancer (NSCLC).

The treatment demonstrated durable responses, with a median duration of response (DoR) of 20.2 months for treatment-naive patients and 28.6 months for those pretreated, along with a significant intracranial ORR of 85% in patients with CNS metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib in Patients With RET Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial. Drilon, A., Subbiah, V., Gautschi, O., et al.[2023]

In a randomized phase 3 trial involving 212 patients, selpercatinib demonstrated a significantly longer median progression-free survival of 24.8 months compared to 11.2 months for platinum-based chemotherapy, indicating its superior efficacy in treating advanced RET fusion-positive non-small-cell lung cancer (NSCLC).

Selpercatinib also showed a higher objective response rate of 84% compared to 65% for the control treatment, and it was particularly effective in delaying disease progression in the central nervous system, with a hazard ratio of 0.28.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. Zhou, C., Solomon, B., Loong, HH., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

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

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

Selpercatinib: First Approval. [2021]

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

Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001. [2022]

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

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

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

Selpercatinib in Patients With RET Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial. [2023]

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

First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety Analysis of Selpercatinib in Patients with RET Fusion-Positive Non-Small Cell Lung Cancer-Results from the Japanese Subset of a Global Phase 1/2 Study]. [2022]