Trial Title:
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)
NCT ID:
NCT03157128
Condition:
Non-Small Cell Lung Cancer
Medullary Thyroid Cancer
Colon Cancer
Any Solid Tumor
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Colonic Neoplasms
Thyroid Neoplasms
Carcinoma, Neuroendocrine
Thyroid Diseases
Conditions: Keywords:
LOXO-292
KIF5B-RET
M918T
CCDC6-RET
RET-PTC1
NCOA4-RET
RET-PTC
RET-PTC3
RET-PTC4
PRKAR1A-RET
RET-PTC2
GOLGA5-RET
RET-PTC5
ERC1-RET
KTN1-RET
RET-PTC8
HOOK3-RET
PCM1-RET
TRIM24-RET
RET-PTC6
TRIM27-RET
TRIM33-RET
RET-PTC7
AKAP13-RET
FKBP15-RET
SPECC1L-RET
TBL1XR1-RET
BCR-RET
FGRF1OP-RET
RFG8-RET
RET-PTC9
ACBD5-RET
MYH13-RET
CUX1-RET
KIAA1468-RET
FRMD4A-RET
SQSTM1-RET
AFAP1L2-RET
PPFIBP2-RET
EML4-RET
PARD3-RET
G533C
C609F
C609G
C609R
C609S
C609Y
C611F
C611G
C611S
C611Y
C611W
C618F
C618R
C618S
C620F
C620R
C620S
C630R
C630Y
D631Y
C634F
C634G
C634R
C634S
C634W
C634Y
K666E
E768D
L790F
V804L
V804M
A883F
S891A
R912P
CLIP1-RET
Y806C
RET fusion
RET alteration
RET mutation
RET rearrangement
RET translocation
Neoplasms by Site
Neoplasms
Non-Small Cell Lung Cancer
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Cancer of Lung
Cancer of the Lung
Lung Cancer
Neoplasms, Lung
Neoplasms, Pulmonary
Pulmonary Cancer
Pulmonary Neoplasms
Respiratory Tract Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Medullary Thyroid Cancer
Papillary Thyroid Cancer
Thyroid Diseases
Thyroid Neoplasms
Cancer of the Thyroid
Cancer of Thyroid
Neoplasms, Thyroid
Thyroid Ademona
Thyroid Cancer
Thyroid Carcinoma
Endocrine System Diseases
Endocrine Gland Neoplasms
Head and Neck Neoplasms
Thoracic Neoplasms
CNS tumor
Primary CNS tumor
Cancer of Colon
Cancer of the Colon
Colon Cancer
Colon Neoplasms
Colonic Cancer
Neoplasms, Colonic
Malignant tumor of Breast
Mammary Cancer
Mammary Carcinoma, Human
Mammary Neoplasm, Human
Neoplasms, Breast
Tumors, Breast
Human Mammary Carcinoma
Malignant Neoplasm of Breast
Breast Carcinoma
Breast Tumors
Cancer of the Breast
Breast Neoplasms
Breast Cancer
RET Inhibitor
MTC
NSCLC
selpercatinib
neo-adjuvant treatment in early stage NSCLC
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
LOXO-292
Description:
Oral LOXO-292
Arm group label:
LOXO-292
Other name:
Selpercatinib
Other name:
LY3527723
Summary:
This is an open-label, first-in-human study designed to evaluate the safety,
tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib
(also known as LOXO-292) administered orally to participants with advanced solid tumors,
including rearranged during transfection (RET)-fusion-positive solid tumors, medullary
thyroid cancer (MTC) and other tumors with RET activation.
Detailed description:
This is an open-label, multi-center Phase 1/2 study in participants with advanced solid
tumors, including RET fusion-positive solid tumors, MTC, and other tumors with RET
activation. The trial will be conducted in 2 parts: Phase 1 (dose escalation - completed)
and phase 2 (dose expansion). Participants with advanced cancer are eligible if they have
progressed on or are intolerant to available standard therapies, or no standard or
available curative therapy exists, or in the opinion of the Investigator, they would be
unlikely to tolerate or derive significant clinical benefit from appropriate standard of
care therapy, or they declined standard therapy. A dose of 160 milligrams (mg) twice a
day (BID) has been selected as the recommended phase 2 dose (RP2D). Approximately 875
participants with advanced solid tumors harboring a RET gene alteration in tumor and/or
blood will be enrolled to one of seven phase 2 cohorts:
- Cohort 1: Advanced RET fusion positive solid tumor other than NSCLC or thyroid
cancer for participants who progressed on or intolerant to first line therapy (open)
- Cohort 2: Advanced RET fusion positive solid tumor other than NSCLC or thyroid
cancer for treatment naïve participants (open)
- Cohort 3: Advanced RET-mutant MTC participants who progressed on or intolerant to
first line therapy (closed)
- Cohort 4: Advanced RET-mutant MTC participants who are treatment naïve (closed)
- Cohort 5: Advanced RET-altered solid tumor for participants other than NSCLC or
thyroid cancer and RET-mutant MEN2 spectrum tumors (e.g. pheochromocytoma) otherwise
ineligible for cohorts 1-4. See details in inclusion/exclusion criteria (open)
- Cohort 6: Participants otherwise eligible for Cohorts 1-5 who discontinued another
RET inhibitor due to intolerance may be eligible with prior Sponsor approval
(closed)
- Cohort 7: RET fusion positive early-stage non-small cell lung cancer (NSCLC)
participants who are candidates for definitive surgery. Participants will receive
selpercatinib in a neoadjuvant and adjuvant setting. Participants will be followed
for disease recurrence for up to 5 years from the date of surgery (closed)
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
For Phase 1:
- Participants with a locally advanced or metastatic solid tumor that:
- Has progressed on or is intolerant to standard therapy, or
- For which no standard therapy exists, or in the opinion of the Investigator, are not
candidates for or would be unlikely to tolerate or derive significant clinical
benefit from standard therapy, or
- Decline standard therapy
- Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
- A RET gene alteration is not required initially. Once adequate PK exposure is
achieved, evidence of RET gene alteration in tumor and/or blood is required as
identified through molecular assays, as performed for clinical evaluation
- Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as
appropriate to tumor type
- Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance
Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years)
with no sudden deterioration 2 weeks prior to the first dose of study treatment
- Adequate hematologic, hepatic and renal function
- Life expectancy of at least 3 months
For Phase 2: As for phase 1 with the following modifications:
- For Cohort 1: Participants must have received prior standard therapy appropriate for
their tumor type and stage of disease, or in the opinion of the Investigator, would
be unlikely to tolerate or derive clinical benefit from appropriate standard of care
therapy
- Cohorts 1 and 2:
- Enrollment will be restricted to participants with evidence of a RET gene
alteration in tumor
- At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate
to tumor type and not previously irradiated
- Cohorts 3 and 4: Enrollment closed
- Cohort 5:
- Cohorts 1-4 without measurable disease
- MCT not meeting the requirements for Cohorts 3 or 4
- MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with
neuroendocrine features/differentiation, or poorly differentiated thyroid
cancers with other RET alteration/activation may be allowed with prior Sponsor
approval
- cfDNA positive for a RET gene alteration not known to be present in a tumor
sample
- Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who
discontinued another RET inhibitor may be eligible with prior Sponsor approval
- Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET
fusion; determined to be medically operable and tumor deemed resectable by a
thoracic surgical oncologist, without prior systemic treatment for NSCLC
Key Exclusion Criteria (Phase 1 and Phase 2):
- Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
- Cohorts 3 and 4: Enrollment closed
- Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes:
Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another
selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor
approval
- Investigational agent or anticancer therapy (including chemotherapy, biologic
therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal
remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start
of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer
therapy is permitted Note: Potential exception for this exclusion criterion will
require a valid scientific justification and approval from the Sponsor
- Major surgery (excluding placement of vascular access) within 2 weeks prior to
planned start of LOXO-292 (selpercatinib)
- Radiotherapy with a limited field of radiation for palliation within 1 week of
planned start of LOXO-292 (selpercatinib), with the exception of participants
receiving radiation to more than 30% of the bone marrow or with a wide field of
radiation, which must be completed at least 4 weeks prior to the first dose of study
treatment
- Any unresolved toxicities from prior therapy greater than Common Terminology
Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment
with the exception of alopecia and Grade 2, prior platinum-therapy related
neuropathy
- Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or
untreated spinal cord compression. Participants are eligible if neurological
symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to
the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been
performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
- Clinically significant active cardiovascular disease or history of myocardial
infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or
prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds
(msec)
- Participants with implanted pacemakers may enter the study without meeting QTc
criteria due to nonevaluable measurement if it is possible to monitor for QT
changes.
- Participants with bundle branch block may be considered for study entry if QTc
is appropriate by a formula other than Fridericia's and if it is possible to
monitor for QT changes.
- Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or
inducers and certain prohibited concomitant medications
- Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior
systemic therapy for NSCLC.
Gender:
All
Minimum age:
12 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic of Scottsdale
Address:
City:
Scottsdale
Zip:
85259
Country:
United States
Facility:
Name:
City of Hope National Medical Center
Address:
City:
Duarte
Zip:
91010-0269
Country:
United States
Facility:
Name:
University of California - San Diego
Address:
City:
La Jolla
Zip:
92161
Country:
United States
Facility:
Name:
UCLA Medical Center
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Facility:
Name:
Hoag Memorial Hospital Presbyterian
Address:
City:
Newport Beach
Zip:
92663
Country:
United States
Facility:
Name:
Irvine Medical Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Facility:
Name:
UCSF Medical Center at Mission Bay
Address:
City:
San Francisco
Zip:
94115
Country:
United States
Facility:
Name:
Kaiser Permanente
Address:
City:
Santa Clara
Zip:
95051
Country:
United States
Facility:
Name:
Kaiser Permanente Medical Center
Address:
City:
Vallejo
Zip:
94589
Country:
United States
Facility:
Name:
Sarah Cannon Research Institute at HealthOne
Address:
City:
Denver
Zip:
80218
Country:
United States
Facility:
Name:
Yale Cancer Center
Address:
City:
New Haven
Zip:
06510
Country:
United States
Facility:
Name:
Johns Hopkins University
Address:
City:
Washington
Zip:
20016
Country:
United States
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224
Country:
United States
Facility:
Name:
Memorial Hospital Pembroke
Address:
City:
Pembroke
Zip:
33028
Country:
United States
Facility:
Name:
Emory University
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Facility:
Name:
University of Chicago Medicine-Comprehensive Cancer Center
Address:
City:
Chicago
Zip:
60637
Country:
United States
Facility:
Name:
Ochsner Clinic Foundation
Address:
City:
New Orleans
Zip:
70121
Country:
United States
Facility:
Name:
University of Maryland Medical Center
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Facility:
Name:
Massachusetts General Hospital
Address:
City:
Boston
Zip:
02114
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
University of Michigan
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Facility:
Name:
START Midwest
Address:
City:
Grand Rapids
Zip:
49546
Country:
United States
Facility:
Name:
Mayo Clinic
Address:
City:
Rochester
Zip:
55905
Country:
United States
Facility:
Name:
Washington University Medical School
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Facility:
Name:
Comprehensive Cancer Centers of Nevada
Address:
City:
Las Vegas
Zip:
89169
Country:
United States
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263-0002
Country:
United States
Facility:
Name:
NYU Langone
Address:
City:
New York
Zip:
10016
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Facility:
Name:
University of North Carolina
Address:
City:
Chapel Hill
Zip:
27599-7305
Country:
United States
Facility:
Name:
Cleveland Clinic Foundation
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Facility:
Name:
Ohio State University Hospital
Address:
City:
Columbus
Zip:
43210
Country:
United States
Facility:
Name:
Oregon Health and Science University
Address:
City:
Portland
Zip:
97201
Country:
United States
Facility:
Name:
University of Pennsylvania Hospital
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Facility:
Name:
Thomas Jefferson University
Address:
City:
Philadelphia
Zip:
19107
Country:
United States
Facility:
Name:
Vanderbilt University Medical Center
Address:
City:
Nashville
Zip:
37232-6307
Country:
United States
Facility:
Name:
University of Texas Southwestern Medical Center at Dallas
Address:
City:
Dallas
Zip:
75390-9063
Country:
United States
Facility:
Name:
University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Facility:
Name:
Huntsman Cancer Institute
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Facility:
Name:
USO-Virginia Cancer Specialists, PC
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Facility:
Name:
University of Wisconsin-Madison Hospital and Health Clinic
Address:
City:
Madison
Zip:
53792
Country:
United States
Facility:
Name:
Royal North Shore Hospital
Address:
City:
St. Leonards
Zip:
2065
Country:
Australia
Facility:
Name:
Peter MacCallum Cancer Centre
Address:
City:
Melbourne
Zip:
3000
Country:
Australia
Facility:
Name:
BC Cancer Vancouver
Address:
City:
Vancouver
Zip:
V5Z 4E6
Country:
Canada
Facility:
Name:
Rigshospitalet
Address:
City:
Copenhagen
Zip:
2100
Country:
Denmark
Facility:
Name:
Hôpital Européen Georges Pompidou
Address:
City:
Paris
Zip:
75908
Country:
France
Facility:
Name:
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Facility:
Name:
Centre Leon Berard
Address:
City:
Lyon Cedex 08
Zip:
69373
Country:
France
Facility:
Name:
APHM Hôpital de la Timone
Address:
City:
Marseille
Zip:
13385
Country:
France
Facility:
Name:
Institut du Cancer de Montpellier - Val d'aurelle
Address:
City:
Montpellier Cedex 5
Zip:
34298
Country:
France
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif Cedex
Zip:
94805
Country:
France
Facility:
Name:
Universitätsklinikum Würzburg A. ö. R.
Address:
City:
Würzburg
Zip:
97080
Country:
Germany
Facility:
Name:
Universitätsklinikum Köln
Address:
City:
Köln
Zip:
50937
Country:
Germany
Facility:
Name:
Prince of Wales Hospital
Address:
City:
Hong Kong
Country:
Hong Kong
Facility:
Name:
Sheba Medical Center
Address:
City:
Tel Hashomer
Zip:
5265601
Country:
Israel
Facility:
Name:
Shaare Zedek Medical Center
Address:
City:
Jerusalem
Zip:
9103102
Country:
Israel
Facility:
Name:
Soroka Medical Center - Pediatric Outpatient Clinic
Address:
City:
Beer-Sheva
Zip:
8410101
Country:
Israel
Facility:
Name:
Hadassah Medical Center
Address:
City:
Jerusalem
Zip:
91120
Country:
Israel
Facility:
Name:
Istituto Nazionale dei Tumori
Address:
City:
Milano
Zip:
20133
Country:
Italy
Facility:
Name:
Nagoya University Hospital
Address:
City:
Nagoya
Zip:
466-8560
Country:
Japan
Facility:
Name:
National Cancer Center Hospital East
Address:
City:
Kashiwa
Zip:
277-8577
Country:
Japan
Facility:
Name:
Hokkaido University Hospital
Address:
City:
Sapporo
Zip:
060-8648
Country:
Japan
Facility:
Name:
Hyogo Cancer Center
Address:
City:
Akashi
Zip:
673-8558
Country:
Japan
Facility:
Name:
Kanazawa University Hospital
Address:
City:
Kanazawa
Zip:
920-8641
Country:
Japan
Facility:
Name:
Kindai University Hospital
Address:
City:
Osaka Sayama-shi
Zip:
589 8511
Country:
Japan
Facility:
Name:
Tominaga Hospital
Address:
City:
Nagaizumi-cho,Sunto-gun
Zip:
411-8777
Country:
Japan
Facility:
Name:
National Cancer Center Hospital
Address:
City:
Chuo-ku
Zip:
104-0045
Country:
Japan
Facility:
Name:
Japanese Foundation for Cancer Research
Address:
City:
Koto
Zip:
135-8550
Country:
Japan
Facility:
Name:
Tottori University Hospital
Address:
City:
Yonago
Zip:
683-8504
Country:
Japan
Facility:
Name:
National Hospital Organization Kyushu Cancer Center
Address:
City:
Fukuoka
Zip:
811-1395
Country:
Japan
Facility:
Name:
Okayama University Hospital
Address:
City:
Okayama
Zip:
700-8558
Country:
Japan
Facility:
Name:
Osaka City General Hospital
Address:
City:
Osaka
Zip:
534-0021
Country:
Japan
Facility:
Name:
National Cancer Center
Address:
City:
Goyang-si
Zip:
10408
Country:
Korea, Republic of
Facility:
Name:
Seoul National University Bundang Hospital
Address:
City:
Seongnam
Zip:
13620
Country:
Korea, Republic of
Facility:
Name:
Asan Medical Center
Address:
City:
Seoul
Zip:
05505
Country:
Korea, Republic of
Facility:
Name:
Samsung Medical Center
Address:
City:
Seoul
Zip:
06351
Country:
Korea, Republic of
Facility:
Name:
Severance Hospital, Yonsei University Health System
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Facility:
Name:
National Cancer Centre Singapore
Address:
City:
Singapore
Zip:
169610
Country:
Singapore
Facility:
Name:
Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Zip:
8035
Country:
Spain
Facility:
Name:
Hospital Universitario Fundación Jiménez Díaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Facility:
Name:
Hospital Madrid Norte Sanchinarro
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Facility:
Name:
Kantonsspital Luzern
Address:
City:
Luzern 16
Zip:
6000
Country:
Switzerland
Facility:
Name:
Taichung Veterans General Hospital
Address:
City:
Taichung
Zip:
40705, ROC
Country:
Taiwan
Facility:
Name:
National Taiwan University Hospital
Address:
City:
Taipei
Zip:
10002
Country:
Taiwan
Facility:
Name:
Royal Marsden Hospital
Address:
City:
Sutton
Zip:
SM2 5PT
Country:
United Kingdom
Start date:
May 2, 2017
Completion date:
February 28, 2026
Lead sponsor:
Agency:
Loxo Oncology, Inc.
Agency class:
Industry
Collaborator:
Agency:
Eli Lilly and Company
Agency class:
Industry
Source:
Eli Lilly and Company
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT03157128
