What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include tyrosine kinase inhibitors (TKIs) like gefitinib and erlotinib, chemotherapy agents such as pemetrexed and platinum-based drugs, and immunotherapies like pembrolizumab and atezolizumab. Known side effects of TKIs include rash, diarrhea, and liver function abnormalities. Chemotherapy can cause fatigue, nausea, neutropenia, and increased risk of infection. Immunotherapies may lead to immune-related adverse effects such as pneumonitis, colitis, and endocrinopathies. For RET inhibitors like Selpercatinib, common side effects include dry mouth, diarrhea, hypertension, and liver enzyme elevations.

What prior FDA approvals exist?

The FDA has approved several targeted therapies and immunotherapies for the treatment of Non-Small Cell Lung Cancer (NSCLC). For RET fusion-positive NSCLC, selpercatinib (LOXO-292) is a notable RET inhibitor under investigation. Other targeted therapies include osimertinib for EGFR mutations, crizotinib for ALK rearrangements, and sotorasib for KRAS G12C mutations. Immunotherapies such as pembrolizumab and nivolumab, which target PD-1, and atezolizumab, which targets PD-L1, have also been approved for NSCLC. These treatments have significantly advanced the management of NSCLC by offering personalized therapy options based on specific genetic alterations and immune profiles.

What other types of research exist?

Promising novel alternatives to Selpercatinib for NSCLC patients include larotrectinib and entrectinib for NTRK fusion-positive cancers, and pyrotinib and poziotinib for HER2 exon 20 insertion mutations. These therapies have demonstrated significant efficacy in clinical trials and are suitable for patients with specific genetic alterations.

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Tyrosine Kinase Inhibitor

Selpercatinib for Solid Tumors (LIBRETTO-001 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Loxo Oncology, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC

Cohorts 1-4 without measurable disease

Must not have

Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)

Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications

Timeline

Screening 3 weeks

Treatment Varies

Follow Up the first 28 days of treatment (cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the participant discontinues from the study)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new oral drug called selpercatinib in patients with advanced cancers that have specific gene changes. The drug aims to block a gene that helps cancer grow, potentially slowing or stopping the disease.

Who is the study for?

This trial is for people with advanced solid tumors, RET fusion-positive solid tumors, or medullary thyroid cancer who have tried standard treatments without success or can't tolerate them. They must have a life expectancy of at least 3 months and good organ function. People with certain genetic alterations may join only after Sponsor approval. Those who've had recent major surgery, other cancer therapies, or untreated brain metastases are excluded.

What is being tested?

The study tests Selpercatinib (LOXO-292), an oral medication targeting specific genetic changes in tumors. It's given to participants with various types of advanced cancers to assess its safety and how well it works against these cancers.

What are the potential side effects?

While the exact side effects aren't listed here, common ones for drugs like Selpercatinib include fatigue, nausea, liver issues, high blood pressure, dry mouth/skin problems and potential heart rhythm abnormalities.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My lung cancer is in an early stage, operable, and has not been treated yet.

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My cancer cannot be measured by standard tests.

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My tumor has a RET gene alteration.

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I have at least one tumor that can be measured and hasn't been treated with radiation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not had major surgery in the last 2 weeks.

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I am not taking strong drugs that affect liver enzymes or forbidden medications.

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I haven't had a heart attack in the last 6 months and my heart's electrical cycle is normal.

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I have not had any systemic therapy for my lung cancer.

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I have previously been treated with a RET inhibitor.

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I haven't taken any experimental cancer treatments recently.

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My cancer has a known genetic mutation driving its growth.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ the first 28 days of treatment (cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the participant discontinues from the study)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~the first 28 days of treatment (cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the participant discontinues from the study)

This trial's timeline: 3 weeks for screening, Varies for treatment, and the first 28 days of treatment (cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the participant discontinues from the study) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1: MTD

Phase 1: RP2D

Phase 2: Objective Response Rate

Secondary study objectives

Phase 1 and 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib)

Phase 1 and 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib)

Phase 1: Number of Participants with a Treatment-Related Adverse Event(s) (TRAE[s])

+12 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: LOXO-292Experimental Treatment1 Intervention

Phase 1 - Multiple doses of LOXO-292 (selpercatinib) Phase 2 - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) often involve targeted therapies that inhibit specific molecular pathways critical for tumor growth and survival. For instance, Selpercatinib is a RET inhibitor that targets RET fusion-positive tumors by blocking the RET kinase activity, thereby inhibiting tumor cell proliferation and survival. Similarly, other targeted therapies include EGFR inhibitors (e.g., osimertinib, erlotinib) that block the epidermal growth factor receptor, and ALK inhibitors (e.g., crizotinib) that target the anaplastic lymphoma kinase. These treatments are crucial for NSCLC patients as they offer a more personalized approach, leading to better efficacy and potentially fewer side effects compared to traditional chemotherapy. By targeting specific genetic mutations or alterations, these therapies can significantly improve outcomes and quality of life for patients with advanced NSCLC.

Tailoring tyrosine kinase inhibitors to fit the lung cancer genome.