Selpercatinib for Cancer in Children

(LIBRETTO-121 Trial)

Recruiting at34 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Eli Lilly and Company

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This is an open-label, multi-center Phase 1/2 study of oral LOXO-292 in pediatric participants with an activating rearranged during transfection (RET) alteration and an advanced solid or primary CNS tumor.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you have uncontrolled thyroid issues that required a change in medication in the last 7 days, you may not be eligible.

What data supports the idea that Selpercatinib for Cancer in Children is an effective drug?

The available research shows that Selpercatinib has been effective in treating certain types of cancer, specifically RET fusion-positive non-small-cell lung cancer and thyroid cancer. In clinical trials, patients treated with Selpercatinib experienced strong and lasting responses, even those who had previously undergone other treatments. The drug was generally well-tolerated, with manageable side effects. Although the studies focus on adults, these results suggest that Selpercatinib could be a promising option for treating similar cancers in children. ^{1 2 3 4 5}

What safety data is available for Selpercatinib in treating cancer?

Selpercatinib, also known as Retevmo, has been evaluated in several clinical trials, including the phase I/II LIBRETTO-001 trial. It has shown a manageable safety profile with common adverse events such as hypertension, elevated liver enzymes, edema, diarrhea, fatigue, and dry mouth. Most adverse events were manageable with dose adjustments, and only a small proportion of patients discontinued due to treatment-related adverse events. The drug has been approved for various RET fusion-positive cancers, indicating its safety and efficacy in these conditions. ^{1 2 3 6 7}

Is the drug Selpercatinib a promising treatment for cancer in children?

Selpercatinib is a promising drug because it has been approved for treating certain types of cancer in adults, showing strong and lasting effects. It targets specific cancer changes, helping to stop cancer growth. This success in adults suggests it could be effective for children with similar cancer types. ^{1 2 5 8 9}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for children with advanced solid tumors or brain tumors that have a specific genetic change called RET alteration. They must be stable, able to take oral medication, and not pregnant. Participants need functioning major organs and haven't had recent surgery or uncontrolled diseases.

Inclusion Criteria

My blood, liver, and kidney functions are all within normal ranges.

I can take medication by mouth or through a tube in my stomach.

My cancer has a RET gene mutation.

Exclusion Criteria

I am not allergic to LOXO-292 or its liquid form ingredients.

I haven't had a heart attack or uncontrolled heart issues in the last 6 months.

I have a severe nutrient absorption problem.

Treatment Details

Interventions

• LOXO-292 (Kinase Inhibitor)

Trial Overview The study tests LOXO-292 (Selpercatinib), an oral medication for pediatric patients with certain types of thyroid cancer, soft tissue sarcoma, and other related conditions. It's designed to see how well it works in those who've tried standard treatments without success.

Participant Groups

Group I: LOXO-292 Experimental Treatment 1 Intervention

Phase 1- Dose Escalation and determination of MTD; multiple dose levels of LOXO-292 to be evaluated; Phase 2 - The MTD/recommended dose from Phase 1

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead 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

Loxo Oncology, Inc.

Industry 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

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]

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 case series of 8 patients with RET-altered advanced non-small-cell lung cancer (NSCLC) and brain metastases, selpercatinib showed a high overall systemic response rate of 75%, with significant intracranial activity where 80% of patients with measurable CNS lesions achieved a confirmed response.

Despite 63% of patients experiencing grade ≥3 treatment-related adverse events, there were no treatment discontinuations due to these adverse effects, indicating that selpercatinib can be administered safely while providing meaningful clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial Activity of Selpercatinib in Chinese Patients With Advanced RET Fusion-Positive Non-Small-Cell Lung Cancer in the Phase II LIBRETTO-321 Trial. Cheng, Y., Huang, D., Zhou, J., 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]

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]

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 is the first FDA-approved selective RET inhibitor that targets oncogenic RET fusion proteins, making it a significant advancement in cancer treatment.

It works by binding to the RET kinase active site, inhibiting the activity of mutated RET proteins that drive tumor growth, thus blocking signals that promote cell proliferation and survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib: First approved selective RET inhibitor. Oliveira, LCB., Mulligan, LM.[2023]

Selpercatinib is a highly effective RET-selective tyrosine kinase inhibitor, showing strong efficacy and safety in treating advanced non-small-cell lung cancer (NSCLC) with RET fusions, which are common genetic alterations in this cancer type.

The drug is currently approved for adult patients with metastatic RET fusion-positive NSCLC, and it demonstrates both systemic and intracranial efficacy, making it a promising treatment option in the evolving landscape of targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib in RET-fusion positive metastatic non-small cell lung cancer: achievements and gray areas. Belluomini, L., Avancini, A., Pasqualin, L., et al.[2022]

References

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

Selpercatinib: First Approval. [2021]

2. France pubmed.ncbi.nlm.nih.gov

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

3. 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]

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

Intracranial Activity of Selpercatinib in Chinese Patients With Advanced RET Fusion-Positive Non-Small-Cell Lung Cancer in the Phase II LIBRETTO-321 Trial. [2023]

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

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

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

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

7. 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]

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

Selpercatinib: First approved selective RET inhibitor. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Selpercatinib in RET-fusion positive metastatic non-small cell lung cancer: achievements and gray areas. [2022]