Clinical trial NCT05241834: A Study of LOXO-260 in Cancer Patients With a Change in a Particular Gene (RET) That Has Not Responded to Treatment
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Thyroid Neoplasms
Keywords: Solid tumors with RET alteration
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2022-02-16
Enrollment: 110
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1 a: To determine the MTD/RP2D of LOXO-260: Dose limiting toxicity (DLT) rate
timeFrame: During the first 28-day cycle of LOXO-260 treatment
Secondary outcomes:
measure: Phase 1b: To assess the antitumor activity: Overall response rate (ORR)
timeFrame: Up to approximately 24 months or 2 years
measure: To characterize the PK properties of LOXO-260: Mean concentration of LOXO-260
timeFrame: Up to approximately 24 months or 2 years
measure: To assess the antitumor activity of LOXO-260: ORR
timeFrame: Up to approximately 24 months or 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mission Bay
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medicine-Comprehensive Cancer Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhône-Alpes
city: Villejuif
country: France
facility: Institut Gustave Roussy (Igr)
Study officials:
affiliation: Eli Lilly and Company
name: Emin Avsar
role: STUDY_DIRECTOR
References: