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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms
• Intervention / Treatment: Drug: LOXO-260

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69008
    • Centre Leon Berard
  • Villejuif, France, 94805
    • Institut Gustave Roussy (Igr)
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • San Francisco, California, United States, 94158
      • UCSF Medical Center at Mission Bay
  • Georgia
    • Atlanta, Georgia, United States, 30329-5102
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine-Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210-1257
      • Ohio State University Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1A: LOXO-260 Dose Escalation; LOXO-260 administered orally	Drug: LOXO-260; Oral; Other Names: LY3838915
Experimental: Phase 1B: LOXO-260 Dose Expansion; LOXO-260 administered orally	Drug: LOXO-260; Oral; Other Names: LY3838915

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Loxo Oncology, Inc.
• Investigators: Study Director: Emin Avsar, Eli Lilly and Company

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2022
• Primary Completion (Actual): September 17, 2024
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 16, 2022

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Solid tumors with RET alteration
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Thyroid Diseases; Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms
• Other Study ID Numbers: 18381; LOXO-NGR-21001 (Other Identifier: Eli Lilly and Company); J3T-OX-JZTA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No