What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include chemotherapy agents such as carboplatin, paclitaxel, and etoposide, as well as targeted therapies like pembrolizumab and lorlatinib. The side effects of these treatments can vary but often include fatigue, nausea, increased liver function tests, and hypercholesterolemia. Serious adverse events can occur, such as cardiac failure and pulmonary hemorrhage. For RET gene inhibitors like LOXO-260, the study aims to learn more about their specific safety and side effects, but they may share similar adverse effects with other targeted therapies.

What prior FDA approvals exist?

Several FDA-approved treatments for Non-Small Cell Lung Cancer (NSCLC) target specific genetic mutations. For instance, osimertinib targets EGFR mutations, and crizotinib targets ALK and ROS1 rearrangements. Additionally, pembrolizumab and atezolizumab are approved for patients with high PD-L1 expression. While LOXO-260 is a RET gene inhibitor under investigation, selpercatinib and pralsetinib are already FDA-approved RET inhibitors for NSCLC. These targeted therapies represent a significant advancement in personalized cancer treatment.

What other types of research exist?

Promising alternatives to LOXO-260 for NSCLC patients with RET gene alterations include pralsetinib (BLU-667) and vandetanib. Pralsetinib has shown clinical activity in patients with RET fusion-positive solid tumors, and vandetanib has demonstrated efficacy and safety in advanced medullary thyroid cancer, which may translate to NSCLC. Additionally, entrectinib and larotrectinib, which target NTRK gene fusions, may also be considered for their broad-spectrum kinase inhibition properties.

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Kinase Inhibitor

LOXO-260 for Non-Small Cell Lung Cancer

Phase 1

Waitlist Available

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

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

Must have

Have received a prior selective RET inhibitor.

Have discontinued all previous treatments for cancer with resolution of any significant AEs, and of all clinically significant toxic effects of prior locoregional therapy, surgery, radiotherapy, or systemic anticancer therapy.

Must not have

Patients treated with drugs known to be strong inhibitors or inducers of cytochrome P450 3A (CYP3A).

Phase 1b expansion: Patients harboring known activating bypass alterations outside RET that may confer resistance to LOXO-260.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 24 months or 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing LOXO-260, a new drug for treating cancers with a specific genetic change in the RET gene. The drug aims to block this gene to stop cancer cells from growing. The study will check if the drug is safe and effective over a period of time. Selpercatinib (LOXO-292), a predecessor to LOXO-260, has shown marked and durable antitumor activity in patients with RET-altered tumors.

Who is the study for?

This trial is for adults with non-small cell lung or thyroid cancer linked to a specific gene change (RET) who've tried other treatments without success. They should be in good physical condition, have had no recent disease progression, and their organs must function well. Children over 12 may join in some cases.

What is being tested?

LOXO-260 is being tested for safety and effectiveness on cancers with the RET gene alteration. Participants will receive LOXO-260 for up to two years or longer if beneficial, monitoring how it affects their cancer's progression.

What are the potential side effects?

While not explicitly listed here, side effects of LOXO-260 could include typical reactions seen with cancer therapies such as fatigue, nausea, liver issues, blood count changes or allergic reactions; specifics would emerge from the study.

Eligibility Criteria

Inclusion Criteria

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

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I have been treated with a RET inhibitor before.

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I have stopped all cancer treatments and recovered from major side effects.

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My cancer is advanced and cannot be removed by surgery, and it has a RET fusion or mutation.

Exclusion Criteria

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

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I am not taking medication that strongly affects liver enzyme CYP3A.

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My cancer has specific genetic changes making it resistant to certain treatments.

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I do not have any active fungal, bacterial, or untreated viral infections.

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My condition can be treated with the goal of curing it.

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I have symptoms from cancer that has spread to my brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 24 months or 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 24 months or 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 24 months or 2 years 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 a: To determine the MTD/RP2D of LOXO-260: Dose limiting toxicity (DLT) rate

Secondary study objectives

Phase 1b: To assess the antitumor activity: Overall response rate (ORR)

To assess the antitumor activity of LOXO-260: ORR

To characterize the PK properties of LOXO-260: Mean concentration of LOXO-260

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Phase 1B: LOXO-260 Dose ExpansionExperimental Treatment1 Intervention

LOXO-260 administered orally

Group II: Phase 1A: LOXO-260 Dose EscalationExperimental Treatment1 Intervention

LOXO-260 administered orally

0 / 8Eligibility 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) include targeted therapies and immunotherapies. Targeted therapies, such as EGFR inhibitors (osimertinib, erlotinib) and ALK inhibitors, work by blocking specific proteins that drive cancer cell growth. RET gene inhibitors, like LOXO-260, specifically target mutations in the RET gene, which can lead to uncontrolled cell proliferation. Immunotherapies, such as PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab), enhance the immune system's ability to recognize and destroy cancer cells. These treatments are crucial for NSCLC patients as they offer more personalized and effective options, especially for those with specific genetic mutations like RET, leading to better outcomes and potentially fewer side effects compared to traditional chemotherapy.

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