A Study of LOXO-260 in Cancer Patients With a Change in a Particular Gene (RET) That Has Not Responded to Treatment

Study Overview
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Brief Summary
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The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-260. LOXO-260 may be used to treat cancer that has a change in a particular gene (known as the RET gene). Participation could last up to 24 months (2 years) and possibly longer if the disease does not get worse.

Official Title
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A Phase 1 Study of Oral LOXO-260 in Patients With RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors With RET Activation Refractory to Selective RET Inhibitors

Conditions
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Carcinoma, Non-Small-Cell Lung, Thyroid Neoplasms

Intervention / Treatment
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* Drug: LOXO-260


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be ≥ 18 years of age at the time of signing the informed consent (Phase 1a and Phase 1b). Patients 12 years and older may be enrolled in Phase 1b for countries and sites where approved. Must have evidence of a previously documented RET fusion (solid tumors) or RET mutation (MTC or MEN2-associated cancers) that is a histological or a cytological proven diagnosis of locally advanced, unresectable and/or metastatic cancer and meet cohort-specific criteria. Have received a prior selective RET inhibitor. Eastern Cooperative Oncology Group (ECOG) score of 0 to 1 (age > 16 years), Karnofsky Performance Status (KPS) ≥ 80 (age > 16 years), or Lansky Performance Status (LPS) ≥ 40% (age < 16 years). 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. Have adequate organ function. Phase 1b expansion: Patients must have measurable disease per RECIST v 1.1. Phase 1b expansion: Molecular Pathology Results (including RET and other genes) from a sample, blood or tissue, taken on or after RET selective treatment. Exclusion Criteria: Disease suitable for local therapy administered with curative intent. Have an active fungal, bacterial, and/or active untreated viral infection. The patient has a serious pre-existing medical condition(s). Have symptomatic CNS malignancy or metastasis. Patients treated with drugs known to be strong inhibitors or inducers of cytochrome P450 3A (CYP3A). Progression of disease within 4 months of starting a prior selective RET inhibitor. Phase 1b expansion: Patients harboring known activating bypass alterations outside RET that may confer resistance to LOXO-260.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1A: LOXO-260 Dose Escalation<br>LOXO-260 administered orally | Drug: LOXO-260<br>* Oral<br>* Other names: LY3838915;|
| Experimental: Phase 1B: LOXO-260 Dose Expansion<br>LOXO-260 administered orally | Drug: LOXO-260<br>* Oral<br>* Other names: LY3838915;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 a: To determine the MTD/RP2D of LOXO-260: Dose limiting toxicity (DLT) rate | DLT rate | During the first 28-day cycle of LOXO-260 treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: To assess the antitumor activity: Overall response rate (ORR) | ORR per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 | Up to approximately 24 months or 2 years | 
| To characterize the PK properties of LOXO-260: Mean concentration of LOXO-260 | PK: Mean concentration of LOXO-260 | Up to approximately 24 months or 2 years | 
| To assess the antitumor activity of LOXO-260: ORR | ORR per RECIST 1.1 | Up to approximately 24 months or 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumors with RET alteration