Selpercatinib for Solid Tumors and Lymphomas

Not currently recruiting at 192 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of selpercatinib (RETEVMO) for individuals with advanced solid tumors, lymphomas, or specific disorders with certain genetic changes. The main goal is to determine if selpercatinib can shrink tumors by blocking cancer cell growth. Suitable participants have tumors with specific genetic alterations affecting the RET pathway and have not previously received selpercatinib or similar drugs. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that selpercatinib is likely to be safe for humans?

Research has shown that selpercatinib, the treatment in this trial, has a well-known safety record. In earlier studies, side effects were manageable, allowing most patients to continue treatment with some dose adjustments if needed. Importantly, the FDA has already approved selpercatinib for treating certain thyroid cancers in adults and teenagers, indicating a recognized level of safety for similar conditions. Overall, selpercatinib is a targeted therapy designed to stop cancer cells from growing by focusing on specific genetic changes. This targeted approach often helps control side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about selpercatinib because it offers a novel approach to treating solid tumors and lymphomas. Unlike standard treatments, which often rely on chemotherapy or radiation, selpercatinib specifically targets and inhibits the RET (rearranged during transfection) kinase, a protein that can drive cancer growth in some patients. This targeted mechanism means selpercatinib has the potential to be more effective and less toxic than traditional therapies. Additionally, its oral administration makes it more convenient for patients compared to some existing treatments that require intravenous delivery.

What evidence suggests that selpercatinib might be an effective treatment for solid tumors and lymphomas?

Research has shown that selpercatinib may help treat certain cancers with changes in the RET gene. One study found that 44% of patients with RET fusion-positive solid tumors experienced tumor shrinkage, with some tumors disappearing completely. The treatment also demonstrated long-lasting effects, indicating that benefits can persist over time. Selpercatinib has already received approval for some uses, proving its effectiveness for certain cancer types. These findings suggest that selpercatinib could be a valuable option for patients with specific genetic changes in their tumors. Participants in this trial will receive selpercatinib as part of the study treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Andrea T Franson

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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™) 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 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]

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 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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10524590/

FDA Approval Summary: Selpercatinib for the treatment of ...

Table 2: Efficacy Results in Patients with RET Fusion-Positive Solid Tumors in Study LIBRETTO-001. ; Complete response, 4.9% ; Partial response, 39% ; Duration of ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38201566/

An Exploratory Interpatient Analysis of LIBRETTO-001

15.2%; and TC: 81.8% vs. 31.8%). First-line selpercatinib use is associated with improved outcomes compared to first-line comparator therapies ...

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.746

Durable efficacy of selpercatinib in patients with RET ...

Conclusions: Selpercatinib continued to demonstrate durable antitumor activity and tolerable safety in pts with RET fusion+ cancers across ...

4.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-selpercatinib-pediatric-patients-two-years-and-older-ret-altered

FDA grants accelerated approval to selpercatinib

The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR). The confirmed ORR (RECIST 1.1), ...

5.

retevmo.lilly.com

retevmo.lilly.com/hcp/efficacy/libretto-001

Efficacy | LIBRETTO-001 Trial | Retevmo® (selpercatinib)

Retevmo was studied in 14 additional advanced or metastatic RET fusion-positive solid tumors · ORR was 44% (95% CI: 28, 60); 4.9% CR + 39% PR · Median DoR was ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39471424/

Long-term safety of selpercatinib for Rearranged during ...

Long-term treatment with selpercatinib is feasible. AEs are manageable with dose modifications, allowing most patients to continue safely on therapy.

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.10022

Safety and efficacy of selpercatinib in pediatric patients ...

Selpercatinib is a highly selective and potent CNS-penetrant oral RET inhibitor, approved for treatment of RET-driven thyroid cancer in adult and adolescent ...

8.

academic.oup.com

academic.oup.com/oncolo/article/29/12/1068/7849621

Long-term safety of selpercatinib for Rearranged during ...

Long-term treatment with selpercatinib is feasible. AEs are manageable with dose modifications, allowing most patients to continue safely on therapy.

9.

research.chop.edu

research.chop.edu/cornerstone-blog/is-selpercatinib-safe-effective-for-children-with-ret-altered-solid-tumors

Is Selpercatinib Safe, Effective for Children With RET ...

Selpercatinib is the first targeted cancer therapy for pediatric patients 2 years of age and older with RET gene alterations.

10.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)01422-4/fulltext

O14-2 Updated tumor agnostic efficacy of selpercatinib in ...

Safety profile was consistent as previously reported. Conclusions. Selpercatinib continued to demonstrate durable antitumor activity in pts with RET fusion+ ...