Selpercatinib for Non-Small Cell Lung Cancer

(LIBRETTO-432 Trial)

Recruiting at 403 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

152 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if the drug selpercatinib can safely and effectively prevent lung cancer from returning in patients who have had treatment. It focuses on people with early-stage lung cancer. The drug works by blocking proteins that help cancer cells grow.

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.

What data supports the effectiveness of the drug selpercatinib for non-small cell lung cancer?

Selpercatinib has shown strong and lasting responses in patients with advanced RET fusion-positive non-small cell lung cancer, including those who have not been treated before and those who have already received chemotherapy. It is effective in treating cancer that has spread to the brain and has a manageable safety profile, with most side effects being mild and treatable. ^{1 2 3 4 5}

What is known about the safety of Selpercatinib for treating non-small cell lung cancer?

Selpercatinib is generally considered safe for treating non-small cell lung cancer, with most side effects being manageable. Common side effects include high blood pressure and elevated liver enzymes, and some patients may experience gastrointestinal issues. Serious side effects are rare, and most can be managed by adjusting the dose. ^{2 3 6 7 8}

What makes the drug selpercatinib unique for treating non-small cell lung cancer?

Selpercatinib is unique because it is a highly selective RET kinase inhibitor that is effective in treating RET fusion-positive non-small cell lung cancer, including cases with brain metastases. It is taken orally and has shown strong and lasting responses, even in patients who have not responded to other treatments. ^{1 2 3 4 5}

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 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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 (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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer. [2022]

2. 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]

3. France pubmed.ncbi.nlm.nih.gov

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

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

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

5. 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]

6. 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]

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

Selpercatinib: First Approval. [2021]

8. Switzerland 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. [2023]