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

Phase 1

Active, not recruiting

• Conditions: Thyroid Neoplasms; Carcinoma, Non-Small-Cell Lung
• Interventions: Drug: LOXO-260

• Registration Number: NCT05241834
• Lead Sponsor: Eli Lilly and Company

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-08
• Study First Submitted QC: 2022-02-08
• Study First Posted: 2022-02-16
• Study Start: 2022-03-23
• Primary Completion: 2024-09-17
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-03
• Last Update Posted: 2025-09-04
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 70

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1B: LOXO-260 Dose Expansion	LOXO-260	LOXO-260 administered orally
Phase 1A: LOXO-260 Dose Escalation	LOXO-260	LOXO-260 administered orally

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (16)

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

UCSF Medical Center at Mission Bay; 🇺🇸 San Francisco, California, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Chicago Medicine-Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

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