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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05241834
• Other study ID #: LOXO-NGR-21001
• Secondary ID: J3T-OX-JZTA
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 23, 2022
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• LOXO-260
Oral

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	University of Chicago Medicine-Comprehensive Cancer Center	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University Hospital	Columbus	Ohio
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	UCLA Medical Center	Los Angeles	California
United States	Sarah Cannon Cancer Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of California, San Francisco Medical Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	To assess the antitumor activity of LOXO-260: ORR	ORR per RECIST 1.1	Up to approximately 24 months or 2 years

External Links

•   A Study of LOXO-260 in Cancer Patients with a Change in a Particular Gene (RET) that has not Responded to Treatment