CLINICAL TRIALS PROFILE FOR RETEVMO

All Clinical Trials for RETEVMO

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03155620 ↗	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)	Recruiting	National Cancer Institute (NCI)	Phase 2	2017-07-24	This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
NCT04320888 ↗	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial	Recruiting	Children's Oncology Group	Phase 2	2020-09-14	This phase II pediatric MATCH trial studies how well selpercatinib works in treating patients with solid tumors that have spread to other places in 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.
NCT04320888 ↗	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial	Recruiting	National Cancer Institute (NCI)	Phase 2	2020-09-14	This phase II pediatric MATCH trial studies how well selpercatinib works in treating patients with solid tumors that have spread to other places in 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.
NCT04759911 ↗	Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer	Recruiting	M.D. Anderson Cancer Center	Phase 2	2021-02-26	This phase II trial studies the effect of selpercatinib given before surgery in treating patients with thyroid cancer whose tumors have RET alterations (changes in the genetic material [deoxyribonucleic acid (DNA)]). Selpercatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving selpercatinib before surgery may help shrink the tumors and help control the disease.
NCT05364645 ↗	A Randomized Phase II Study of Carboplatin and Pemetrexed With or Without Selpercatinib in Patients With Non-squamous RET Positive Stage IV Non-small Cell Lung Cancer and Progression of Disease on Prior RET Directed Therapy, A Lung-MAP Treatment Tri	Not yet recruiting	National Cancer Institute (NCI)	Phase 2	2022-12-09	This phase II Lung-MAP treatment trial tests whether carboplatin and pemetrexed with or without selpercatinib works to shrink tumors in patients with RET fusion-positive non-small cell lung cancer that is stage IV or has not responded to previous RET directed therapy. Chemotherapy drugs, such as carboplatin and pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Selpercatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving selpercatinib in combination with carboplatin and pemetrexed may help lower the chance of the cancer growing and spreading.
NCT05364645 ↗	A Randomized Phase II Study of Carboplatin and Pemetrexed With or Without Selpercatinib in Patients With Non-squamous RET Positive Stage IV Non-small Cell Lung Cancer and Progression of Disease on Prior RET Directed Therapy, A Lung-MAP Treatment Tri	Not yet recruiting	Southwest Oncology Group	Phase 2	2022-12-09	This phase II Lung-MAP treatment trial tests whether carboplatin and pemetrexed with or without selpercatinib works to shrink tumors in patients with RET fusion-positive non-small cell lung cancer that is stage IV or has not responded to previous RET directed therapy. Chemotherapy drugs, such as carboplatin and pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Selpercatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving selpercatinib in combination with carboplatin and pemetrexed may help lower the chance of the cancer growing and spreading.
NCT05668962 ↗	Restor. I-131 Upt. + Selpercatinib in RET F-P RAI-R TC	Not yet recruiting	Eli Lilly and Company	Phase 2	2023-01-01	This research is being done to determine the efficacy of selpercatinib to restore radioactive iodine (I-131) uptake and allow for I-131 treatment in people with RET fusion-positive radioiodine-refractory thyroid cancer. This research study involves the study drug selpercatinib in combination with standard of care treatments, I-131 and thyrotropin alfa (rhTSH).

Clinical Trial Conditions for RETEVMO

Condition Name

Condition Name for RETEVMO
Intervention	Trials
Recurrent Malignant Solid Neoplasm	2
Refractory Malignant Solid Neoplasm	2
Recurrent Ependymoma	2
Recurrent Medulloblastoma	2

Condition MeSH

Condition MeSH for RETEVMO
Intervention	Trials
Carcinoma	3
Medulloblastoma	2
Neuroectodermal Tumors, Primitive	2
Glioma	2

Clinical Trial Locations for RETEVMO

Trials by Country

Trials by Country for RETEVMO
Location	Trials
United States	95
Puerto Rico	2

Trials by US State

Trials by US State for RETEVMO
Location	Trials
Texas	3
Massachusetts	3
Illinois	2
Wisconsin	2
Idaho	2

Clinical Trial Progress for RETEVMO

Clinical Trial Phase

Clinical Trial Phase for RETEVMO
Clinical Trial Phase	Trials
Phase 2	5

Clinical Trial Status

Clinical Trial Status for RETEVMO
Clinical Trial Phase	Trials
Recruiting	3
Not yet recruiting	2

Clinical Trial Sponsors for RETEVMO

Sponsor Name

Sponsor Name for RETEVMO
Sponsor	Trials
National Cancer Institute (NCI)	3
Children's Oncology Group	1
M.D. Anderson Cancer Center	1

Sponsor Type

Sponsor Type for RETEVMO
Sponsor	Trials
Other	4
NIH	3
Industry	1

Clinical Trials Update, Market Analysis, and Projection for RETEVMO (Retevmo, Selpercatinib)

Last updated: October 30, 2025

Introduction

RETEVMO (selpercatinib) is a targeted therapy developed by Eli Lilly and Company, approved by the FDA in May 2020 for the treatment of specific cancers harboring RET gene alterations, including non-small cell lung cancer (NSCLC), thyroid cancers, and other RET fusion-positive tumors. The drug's mechanism of action involves selectively inhibiting RET proto-oncogene mutations and fusions, crucial drivers in various malignancies. As precision oncology advances, RETEVMO's market trajectory hinges on ongoing clinical development, regulatory reviews, and evolving therapeutic landscapes.

This comprehensive analysis provides an update on RETEVMO’s clinical trial pipeline, evaluates its current market status, projects future growth, and assesses competitive and regulatory considerations shaping its commercial outlook.

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Clinical Trials Update

Clinical Development Overview

Since its FDA approval, RETEVMO has demonstrated considerable efficacy in Phase 1/2 trials, notably the LIBRETTO-001 study, which remains pivotal in understanding its safety and efficacy profile. The drug has received additional approvals outside the U.S., fueling extension of its clinical evaluation globally.

Current and Ongoing Trials

• Regulatory Approvals & Extensions:
  Beyond the initial indications for RET fusion-positive NSCLC and thyroid cancers, Eli Lilly has sought expanded indications. The drug received accelerated approval for RET fusion-positive NSCLC, with full approvals pending based on confirmatory studies.

• Phase 3 Trials:
  The key ongoing Phase 3 trials include LIBRETTO-431, evaluating RETEVMO in larger, randomized cohorts versus standard therapies. For RET fusion-positive NSCLC, the LIBRETTO-431 trial compares RETEVMO with standard chemotherapies and immunotherapies, aiming to establish durable superiority and refine patient selection.

• Additional Indications in Development:
  Trials are underway exploring RETEVMO’s efficacy in medullary thyroid carcinoma (MTC), additional RET fusion-positive tumors, and pediatric tumors. Notably, LIBRETTO-531, a phase 2 trial, assesses efficacy in RET-altered solid tumors, expanding indications beyond current approvals.

• Adverse Events & Safety Profiles:
  Ongoing data primarily reinforce the manageable safety profile noted in earlier studies, with common adverse events including dry mouth, diarrhea, hypertension, and transaminase elevations. Trials continue to monitor for rare but severe adverse effects such as hypertension and myocarditis.

Emerging Data & Future Perspectives

Preliminary data from ongoing trials suggest that RETEVMO retains high response rates (>70%) in RET fusion-positive NSCLC and thyroid cancers. The compound demonstrates promising intracranial activity, an increasingly important factor considering CNS metastases prevalent in lung cancer.

In addition, resistance mechanisms, such as RET kinase domain mutations, are under active investigation. Eli Lilly is developing next-generation RET inhibitors to address acquired resistance, with clinical trials planned or underway, including LY3358028.

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Market Analysis

Current Market Landscape

The global RET inhibitor market is currently niche but rapidly evolving, driven by the growing adoption of molecular diagnostics and expanding indications for RET-targeted therapy.

• Market Size & Revenue:
  As of 2022, the RET-targeted therapy segment is estimated at approximately $250 million, with RETEVMO accounting for the majority of sales, owing to its first-mover advantage and regulatory approvals. Worldwide, sales have grown consistently since launch, driven by increased metastatic NSCLC and thyroid cancer diagnoses.

• Key Competitors:
  The competitive landscape comprises other RET inhibitors in development—primarily Pralsetinib (Gavreto, Bluebird Bio/Eli Lilly), approved slightly prior, and experimental agents like LOXO-292 (Selpercatinib's development code) transitioning into branded status. Limited off-label competition exists from multi-kinase inhibitors like Vandetanib and Cabozantinib, which have less selectivity and higher toxicity profiles.

• Market Penetration & Challenges:
  RETEVMO benefits from a targeted patient population confirmed via genetic testing, but its adoption depends on increased testing rates, reimbursement, and clinician familiarity. Challenges include resistance development and screening limitations.

Regulatory & Reimbursement Dynamics

• Regulatory Trends:
  The expanding indication portfolio, including approvals for pediatric and CNS indications, enhances potential market penetration.

• Reimbursement Environment:
  Payers recognize the clinical benefits, supporting coverage; however, high drug costs (~$15,000/month) pose access challenges, especially in markets with limited diagnostic infrastructure.

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Market Projection & Future Outlook

Projected Growth

Based on current sales momentum, upcoming clinical approvals, and increased diagnostic adoption, the RETEVMO market is projected to grow at a compound annual growth rate (CAGR) of approximately 18-22% over the next five years.

Key Drivers:

• Broadened Indications:
  Expansion into previously unaddressed RET-mutated cancers and pediatric indications will significantly enlarge the target patient population.

• Enhanced Diagnostic Adoption:
  Widespread implementation of next-generation sequencing (NGS) and liquid biopsy techniques will improve identification of RET alterations, increasing eligible patients.

• Resistance Management:
  Development of next-generation RET inhibitors to overcome resistance will sustain long-term sales.

Potential Risks & Limitations

• Competition & Efficacy:
  Emergence of superior or more selective RET inhibitors could erode RETEVMO’s market share.

• Regulatory & Reimbursement Barriers:
  Delays in clinical validation or reimbursement hurdles could hinder revenue growth.

• Resistance & Safety Concerns:
  Resistance mutations may limit durable responses; safety profile considerations could influence physician prescribing patterns.

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Key Takeaways

• Clinical Momentum:
  Ongoing Phase 3 trials are critical to solidify RETEVMO’s position, particularly in demonstrating superiority and durability compared to existing therapies. Positive trial outcomes will catalyze broader approval and utilization.

• Market Expansion:
  The growing use of molecular diagnostics and expanding indications will significantly grow the patient population, fueling revenue uplift.

• Competitive Landscape:
  While RETEVMO maintains a first-mover advantage, aggressive competition from newer RET inhibitors and combination therapies necessitates ongoing R&D investment and strategic positioning.

• Strategic Focus Areas:
  Enhancing diagnostic pathways, addressing resistance mechanisms, and expanding into pediatric and CNS indications are pivotal for sustained growth.

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FAQs

1. What are the primary indications for RETEVMO currently?
   RETEVMO is approved for RET fusion-positive non-small cell lung cancer, medullary thyroid carcinoma, and RET fusion-positive thyroid cancers.

2. How does RETEVMO compare with its main competitor, Pralsetinib?
   Both are selective RET inhibitors with comparable efficacy. RETEVMO gained earlier FDA approval, but emerging data suggest similar intracranial activity and safety profiles. The choice often depends on pricing, physician preference, and regulatory approvals.

3. What are the main safety concerns associated with RETEVMO?
   Common adverse events include diarrhea, dry mouth, hypertension, and elevated liver enzymes. Rare adverse effects like myocarditis require monitoring.

4. What is the outlook for resistance development with RETEVMO?
   Resistance mutations, such as RET kinase domain mutations, can diminish efficacy. Combining RETEVMO with other agents or developing next-generation inhibitors are strategies to address this challenge.

5. Will RETEVMO be reimbursed in emerging markets?
   Reimbursement depends on local policies, diagnostic infrastructure, and cost-effectiveness. As evidence accumulates and pricing strategies adapt, broader access is anticipated.

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References

1. FDA. (2020). "FDA Approves Selpercatinib for RET Fusion-Positive Lung and Thyroid Cancers."
2. Eli Lilly. (2022). "RETEVMO (selpercatinib) Prescribing Information."
3. Lung Cancer News. (2022). "Emerging Data on RETEVMO in CNS Metastases."
4. Market Research Future. (2022). "Global RET Inhibitors Market Size, Trends & Forecast."
5. ClinicalTrials.gov. (2023). "Ongoing Trials for RETEVMO."

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