Selpercatinib for Cancer in Children

(LIBRETTO-121 Trial)

Not currently recruiting at 36 trial locations

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

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eli Lilly and Company

Must not be taking: Selective RET inhibitors

Disqualifiers: Cardiac disease, Infections, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment called LOXO-292 (Selpercatinib) for children with difficult-to-treat tumors. It targets those with a specific change in the RET gene, which can make the cancer hard to control. The trial aims to determine the best dose and evaluate the treatment's effectiveness. Eligible participants have solid or brain tumors that have not improved with other treatments and have a confirmed RET alteration. Participants must be able to take the treatment orally or through a feeding tube. As a Phase 1, Phase 2 trial, it focuses on understanding the treatment's mechanism and measuring its effectiveness in an initial group, offering participants a chance to be among the first to benefit from this promising therapy.

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.

Will I have to stop taking my current medications?

The trial information 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 recently, you may not be eligible.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that selpercatinib, also known as LOXO-292, has been tested in children with specific gene changes linked to tumors. In one study, 27 children aged 2 to 20 received this treatment. The study found that selpercatinib was generally well-tolerated by these young patients. While side effects occurred, they were mostly mild.

Additionally, the FDA has already approved selpercatinib for children 12 and older with a type of thyroid cancer, indicating its safety for that age group.

Overall, while some side effects can occur, previous research has demonstrated positive safety results for selpercatinib. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Selpercatinib is unique because it specifically targets RET gene alterations, which are common in certain types of cancers. Unlike traditional chemotherapy that attacks all rapidly dividing cells, Selpercatinib focuses on cancer cells with these specific genetic changes, potentially resulting in fewer side effects. Researchers are excited about this treatment because it represents a more personalized approach to cancer therapy, aiming to improve outcomes by precisely hitting the genetic drivers of the disease.

What evidence suggests that LOXO-292 might be an effective treatment for cancer in children?

Research has shown that selpercatinib, the investigational treatment in this trial, holds promise for treating certain tumors in children. In one study, 92% of children who responded to the treatment continued to do well after 12 months. Another report found that 52.8% of young patients with these specific tumors responded positively to the treatment. Additionally, selpercatinib demonstrated lasting effects and is generally well-tolerated. These findings suggest that selpercatinib could effectively manage these types of cancers in children. ^{1 3 4 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Participants are enrolled using a rolling 6 dose escalation scheme to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of LOXO-292

28 days per cycle

Days 1 and 8 of Cycle 1, Day 1 of Cycle 3, and Day 8 after intra-participant dose escalation

Phase 2: Dose Expansion

Participants are enrolled into one of four dose expansion cohorts based on tumor histology and genotype, receiving the MTD/recommended dose from Phase 1

Up to 24 months

Approximately every 8 weeks for one year, then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after the last dose

What Are the Treatments Tested in This Trial?

Interventions

• LOXO-292

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.

How Is the Trial Designed?

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

LOXO-292 is already approved in United States for the following indications:

Approved in United States as Retevmo for:

• Non-small cell lung cancer (NSCLC) with RET fusion
• Medullary thyroid cancer (MTC) with RET mutation
• Thyroid cancer with RET fusion

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

Published Research Related to This Trial

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 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 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) 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]

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 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 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]

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]

Citations

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

Safety and efficacy of selpercatinib in pediatric patients ... Results: At the data cut-off (January 13, 2023), 27 pts aged 2-20 yrs were treated with selpercatinib. Tumor types included RET-mutant ...

2. 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-altered ... The median duration of response was not reached, with 92% of responders remaining in response at 12 months. Durable responses were observed in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7450975/

Activity of the Highly Specific RET Inhibitor Selpercatinib ... Selpercatinib has demonstrated durable tumor responses and high tolerability in adolescents and adults with RET-altered cancers, with response rates of 68% ...

4. healio.com healio.com/news/endocrinology/20250728/oral-therapy-confers-durable-response-for-retaltered-pediatric-thyroid-cancer

Oral drug effective for RET-altered pediatric thyroid cancer Selpercatinib conferred an overall response rate of 52.8% among children and adolescents with a RET-altered tumor. · Progression-free survival ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03899792

NCT03899792 | A Study of Oral LOXO-292 (Selpercatinib ... 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) ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/213246s008lbl.pdf

Retevmo - accessdata.fda.gov The safety and effectiveness of RETEVMO have been established in pediatric patients aged 12 years and older for medullary thyroid cancer (MTC) who require ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12543762/

OR28-05 Selpercatinib in Pediatric and Adolescent ... Here we report on the safety and efficacy of selpercatinib in pediatric and adolescent pts with RET-altered solid tumors from the LIBRETTO-121 ...