Selpercatinib for Non-Small Cell Lung Cancer

Recruiting at 305 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

124 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II LUNG-MAP treatment trial studies how well selpercatinib works in treating patients with RET fusion-positive non-small cell lung cancer that is stage IV or has come back (recurrent). Selpercatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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.

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 with brain metastases, as demonstrated in several clinical trials. It is effective for patients who have previously received chemotherapy and those who have not, with manageable side effects. ^{1 2 3 4 5}

Is Selpercatinib safe for humans?

Selpercatinib, also known as RETEVMO, has been shown to have an acceptable safety profile in clinical trials for non-small cell lung cancer. Most side effects were manageable with dose adjustments, and only a few patients stopped treatment due to side effects. Common serious side effects included high blood pressure and elevated liver enzymes. ^{1 2 3 4 6}

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

Selpercatinib is unique because it is a highly selective and potent inhibitor specifically targeting RET (rearranged during transfection) alterations, which are genetic changes found in some cancers. It is taken orally and has shown strong and lasting responses, even in the brain, for patients with RET fusion-positive non-small cell lung cancer, including those who have already tried other treatments. ^{1 2 3 5 7}

Research Team

Yasir Y Elamin

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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™) 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 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]

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]

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 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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

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

Selpercatinib: First Approval. [2021]

3. 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]

4. 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]

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

First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. [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. England pubmed.ncbi.nlm.nih.gov

Selpercatinib in RET-fusion positive metastatic non-small cell lung cancer: achievements and gray areas. [2022]