Selpercatinib for Non-Small Cell Lung Cancer

(LIBRETTO-432 Trial)

Not currently recruiting at 451 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Selective RET inhibitors

Disqualifiers: Other oncogenic drivers, Small cell lung cancer, Interstitial lung disease, Cardiovascular disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether selpercatinib can prevent early-stage non-small cell lung cancer (NSCLC) from returning after surgery or radiation. Participants will receive either selpercatinib or a placebo (a pill with no active drug) to compare their effectiveness. The trial suits those who have had certain stages of NSCLC, possess a specific genetic change in their cancer (called a RET gene fusion), and have undergone surgery or radiation aimed at curing the cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that selpercatinib is generally well-tolerated by patients with non-small cell lung cancer (NSCLC). Studies have found that patients with RET fusion-positive NSCLC had positive results with this treatment. Specifically, selpercatinib helped reduce cancer spread, particularly to the brain.

Previous research indicates that the treatment is mostly safe, with most side effects being mild to moderate. Although some patients experienced more serious side effects, these were less common. Overall, the treatment appears safe for most people.

Selpercatinib is already approved for certain types of lung cancer, indicating its safety in other medical settings. This approval provides reassurance about its safety for participants in the current trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Selpercatinib is unique because it specifically targets the RET gene alterations found in some non-small cell lung cancer (NSCLC) cases. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, Selpercatinib zeroes in on this genetic mutation, potentially leading to more effective and personalized treatment with fewer side effects. Researchers are excited about Selpercatinib because it represents a shift towards precision medicine in lung cancer, offering hope for patients with these specific genetic changes.

What evidence suggests that selpercatinib might be an effective treatment for non-small cell lung cancer?

Research shows that selpercatinib effectively treats non-small cell lung cancer (NSCLC) with a specific genetic change known as RET fusion. In this trial, some participants will receive selpercatinib. Studies have shown that it results in a significantly longer time before cancer progression—24.8 months compared to 11.2 months for those not taking the drug. Selpercatinib also led to more patients experiencing tumor shrinkage. These results suggest that selpercatinib could be a promising option for slowing the return of cancer after surgery or radiation in early-stage NSCLC. ^{1 2 6 7 8}

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 people with early-stage non-small cell lung cancer who've had surgery or radiation. They must be in good physical condition, have proper organ function, and a specific RET gene change in their tumor. Participants should not have used certain other cancer drugs before, nor should they have serious illnesses like uncontrolled infections or heart problems.

Inclusion Criteria

I am fully active or can carry out light work.

I finished my main cancer treatment less than 10 weeks ago without chemotherapy, or less than 26 weeks ago with chemotherapy.

I had surgery or radiotherapy for early-stage lung cancer.

Exclusion Criteria

My cancer has come back or gotten worse after treatment.

I have or had lung scarring or inflammation that needed steroids.

I have been treated with a specific medication for cancer before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selpercatinib or placebo orally to evaluate its effectiveness and safety in delaying cancer return

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 9 years

Crossover

Participants on placebo may crossover to selpercatinib if their disease progresses

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Selpercatinib

Trial Overview The study tests if Selpercatinib can prevent cancer from returning compared to a placebo in patients with NSCLC post-surgery or radiation. If the disease worsens on placebo, those participants might switch to Selpercatinib. The trial could last up to three years.

How Is the Trial Designed?

Group I: Selpercatinib Experimental Treatment 1 Intervention

Selpercatinib administered orally.

Group II: Placebo Placebo Group 1 Intervention

Placebo administered orally.

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

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 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 is an effective first-line treatment for RET fusion-positive advanced non-small cell lung cancer (NSCLC), but it can cause significant gastrointestinal adverse events, as demonstrated in a case study of a 37-year-old woman who experienced severe symptoms after 9 months of treatment.

The patient's gastrointestinal toxicity led to treatment interruption and dose reduction, but after resuming at a lower dose, she did not experience a relapse of symptoms, highlighting the need for careful management of side effects in patients receiving selpercatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small bowel edema and lymphocytic duodenitis as severe reversible gastrointestinal toxicity of selpercatinib in RET fusion-positive non-small cell lung cancer: a case report. Scattolin, D., Scagliori, E., Scapinello, A., et al.[2023]

Selpercatinib, a selective RET inhibitor, demonstrated a high objective response rate (ORR) of 87.2% in patients with RET-fusion-positive advanced non-small-cell lung cancer (NSCLC) compared to 66.7% in a real-world control group, indicating its efficacy as a treatment option.

After adjusting for patient characteristics, selpercatinib showed significantly better outcomes in terms of progression-free survival and overall survival compared to both real-world and clinical trial control cohorts, although the findings should be interpreted cautiously due to limitations in data and assumptions made.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer. Rolfo, C., Hess, LM., Jen, MH., et al.[2022]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12378005/

Selpercatinib for RET fusion-positive non-small cell lung cancer Selpercatinib demonstrated significantly longer progression-free survival (24.8 months versus 11.2 months) and higher response rate (84% versus ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-02076

Selpercatinib in RET Fusion–Positive Non–Small Cell ... We report the final efficacy and safety results of selpercatinib in patients with RET fusion–positive non–small cell lung cancer (NSCLC)

3. jnccn.org jnccn.org/view/journals/jnccn/22/2.5/article-HSR24-128.xml

HSR24-128: Real-World Treatment Patterns and ... It has demonstrated superior efficacy versus chemo-immunotherapy in patients with a/mNSCLC. However, there are limited real-world data on selpercatinib use and ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39594790/

Descriptive, Retrospective Findings from Two Databases This study described real-world patient characteristics and outcomes among selpercatinib-treated patients in the United States.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2005653

Efficacy of Selpercatinib in RET Fusion–Positive Non– ... Selpercatinib had durable efficacy, including intracranial activity, with mainly low-grade toxic effects in patients with RET fusion–positive NSCLC.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)00152-1/fulltext

27P Durability of efficacy and safety with selpercatinib in ... Among all NSCLC pts, 26 had measurable CNS metastases at baseline per IRC. Selpercatinib treatment resulted in a CNS ORR of 84.6% (95% CI: 65.1–95.6), with a ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT332541

Updated overall efficacy and safety of selpercatinib in ... Updated overall efficacy and safety of selpercatinib in patients (pts) with RET fusion+ non-small cell lung cancer (NSCLC). ; CBR% (95% CI), n, 84 (78.9, 89.0), ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2309457

First-Line Selpercatinib or Chemotherapy and ... Treatment with selpercatinib led to significantly longer progression-free survival than platinum-based chemotherapy with or without pembrolizumab among ...