Selpercatinib for Non-Small Cell Lung Cancer

Not currently recruiting at 315 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Southwest Oncology Group

Must not be taking: CYP3A4 inhibitors, Proton pump inhibitors

Disqualifiers: Leptomeningeal disease, Brain metastases, Cardiac disease, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 28-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of selpercatinib (RETEVMO) for individuals with advanced or recurring non-small cell lung cancer that has a specific gene change called RET fusion-positive. The treatment may inhibit tumor growth by blocking certain enzymes essential for cancer cells. Individuals diagnosed with RET fusion-positive non-small cell lung cancer who have previously undergone chemotherapy may be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain medications like strong inhibitors or inducers of CYP3A4 or proton pump inhibitors during the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that selpercatinib was tested for safety in patients with RET fusion-positive non-small cell lung cancer. In earlier studies, common side effects included dry mouth, diarrhea, and high blood pressure, affecting about 25% or more of patients. Serious side effects occurred in 44% of patients, though the sources do not provide details.

Selpercatinib is already FDA-approved for treating other types of cancer, indicating that its safety has been studied. However, individual experiences may vary, so discussing any concerns with a doctor is essential. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for non-small cell lung cancer, which often include chemotherapy, radiation, and targeted therapies like EGFR or ALK inhibitors, selpercatinib targets a specific genetic mutation known as RET. This precision approach means selpercatinib can directly interfere with the cancer’s growth mechanisms if the RET mutation is present. Researchers are excited because it offers a more personalized treatment option that could lead to better outcomes for patients with this genetic profile, potentially with fewer side effects than traditional treatments.

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

Research has shown that selpercatinib effectively treats RET fusion-positive non-small cell lung cancer (NSCLC). In one study, patients taking selpercatinib lived without their cancer worsening for an average of 24.8 months, compared to 11.2 months for those not on the treatment. Additionally, 84% of patients responded well to the treatment. Another study found that selpercatinib continues to work over time and remains effective even when the cancer has spread to the brain, with mostly mild side effects. These findings suggest that selpercatinib could be a promising option for people with this type of lung cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Yasir Y Elamin

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer that tests positive for RET fusion. Participants must have tried platinum-based chemotherapy, be able to swallow capsules, and not have other major health issues or recent surgeries. They can't join if they've used anti-RET drugs before or are pregnant/nursing.

Inclusion Criteria

I have no lingering side effects from previous cancer treatments.

My lung cancer is RET fusion-positive.

I have not had cancer before, except for certain types that are exceptions.

Exclusion Criteria

Patients must not be pregnant or nursing, and must use effective contraception during and after the study

I do not have uncontrolled diabetes, high blood pressure, or issues with my digestive system.

I have not had any major surgery in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selpercatinib orally twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 6 months for 2 years and then at the end of 3 years.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Selpercatinib

Trial Overview The study is testing Selpercatinib's effectiveness on stage IV or recurrent non-small cell lung cancer with RET fusion. It aims to see if the drug can halt tumor growth by inhibiting specific enzymes needed by cancer cells.

How Is the Trial Designed?

Group I: Treatment (selpercatinib) Experimental Treatment 1 Intervention

Patients receive selpercatinib orally PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Selpercatinib is already approved in United States, European Union for the following indications:

Approved in United States as RETEVMO for:

• RET fusion-positive or RET mutant thyroid cancers
• non-small cell lung cancer
• advanced or metastatic medullary thyroid cancer
• advanced or metastatic thyroid cancer with RET gene fusion
• locally advanced or metastatic solid tumors with RET gene fusion

Approved in European Union as RETEVMO for:

• RET-driven non-small cell lung cancer
• medullary thyroid cancer
• thyroid cancer

Who Is Running the Clinical Trial?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 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™) 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 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]

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]

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]

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/

Real-World Outcomes of Selective RET Inhibitor ... 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. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/218160s001lbl.pdf

Reference ID: 5396535 - accessdata.fda.gov The most common tumors were NSCLC (45%), MTC (40%), and non-medullary thyroid carcinoma (7%). Serious adverse reactions occurred in 44% of patients who received ...

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

27P Durability of efficacy and safety with selpercatinib in ... In the safety population (NSCLC pts with ≥ 1 dose, N=356), the most common adverse events (AEs in ≥25% pts) were dry mouth, diarrhea, hypertension, increased ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04194944

NCT04194944 | A Study of Selpercatinib (LY3527723) in ... The reason for this study is to see if the study drug selpercatinib compared to a standard treatment is effective and safe in participants with rearranged ...