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A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)
Study Purpose
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.
Recruitment Criteria
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Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
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Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
| Eligible Ages | 12 Years and Over |
| Gender | All |
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.
- - 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 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.
- - 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).
- - 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.
- - 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.
Trial Details
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Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT03157128 |
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Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 1/Phase 2 |
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Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Eli Lilly and Company |
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Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) |
| Principal Investigator Affiliation | Eli Lilly and Company |
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Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
| Overall Status | Active, not recruiting |
| Countries | Australia, Canada, Denmark, France, Germany, Hong Kong, Israel, Italy, Japan, Singapore, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States |
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Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Non-Small Cell Lung Cancer, Medullary Thyroid Cancer, Colon Cancer, Any Solid Tumor |
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).
- - 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.
- - 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.
Arms
Experimental: LOXO-292
Phase 1 - Multiple doses of LOXO-292 (selpercatinib) Phase 2 - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)
Interventions
Drug: - LOXO-292
Oral LOXO-292
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Address
Mayo Clinic of Scottsdale
Scottsdale 5313457, Arizona 5551752, 85259
Status
Address
City of Hope National Medical Center
Duarte 5344147, California 5332921, 91010-0269
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Address
UCLA Medical Center
Los Angeles 5368361, California 5332921, 90095
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Address
Hoag Memorial Hospital Presbyterian
Newport Beach 5376890, California 5332921, 92663
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Address
Kaiser Permanente
Oakland 5378538, California 5332921, 94611-5400
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Address
Irvine Medical Center
Orange 5379513, California 5332921, 92868
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Address
University of California - San Diego
San Diego 5391811, California 5332921, 92103
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Address
UCSF Medical Center at Mission Bay
San Francisco 5391959, California 5332921, 94158
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Address
Kaiser Permanente Medical Center
Walnut Creek 5406990, California 5332921, 94596
Status
Address
Sarah Cannon Research Institute at HealthOne
Denver 5419384, Colorado 5417618, 80218
Status
Address
Yale Cancer Center
New Haven 4839366, Connecticut 4831725, 06520
Status
Address
Mayo Clinic in Florida
Jacksonville 4160021, Florida 4155751, 32224
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Address
Memorial Hospital Pembroke
Pembroke 4168135, Florida 4155751, 33028
Status
Address
Emory University
Atlanta 4180439, Georgia 4197000, 30329-5102
Status
Address
University of Chicago Medicine-Comprehensive Cancer Center
Chicago 4887398, Illinois 4896861, 60637
Status
Address
Ochsner Clinic Foundation
New Orleans 4335045, Louisiana 4331987, 70121
Status
Address
University of Maryland Medical Center
Baltimore 4347778, Maryland 4361885, 21201
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Address
Johns Hopkins University
Baltimore 4347778, Maryland 4361885, 21287
Status
Address
Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926, 02114
Status
Address
Dana-Farber Cancer Institute
Boston 4930956, Massachusetts 6254926, 02215
Status
Address
University of Michigan
Ann Arbor 4984247, Michigan 5001836, 48109
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Address
START Midwest
Grand Rapids 4994358, Michigan 5001836, 49546
Status
Address
Mayo Clinic
Rochester 5043473, Minnesota 5037779, 55905-0002
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Address
Washington University Medical School
St Louis 4407066, Missouri 4398678, 63110
Status
Address
Comprehensive Cancer Centers of Nevada
Las Vegas 5506956, Nevada 5509151, 89169
Status
Address
Roswell Park Cancer Institute
Buffalo 5110629, New York 5128638, 14263
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Address
NYU Langone
New York 5128581, New York 5128638, 10016
Status
Address
Memorial Sloan Kettering Cancer Center
New York 5128581, New York 5128638, 10065
Status
Address
University of North Carolina
Chapel Hill 4460162, North Carolina 4482348, 27514
Status
Address
Cleveland Clinic Foundation
Cleveland 5150529, Ohio 5165418, 44195
Status
Address
Ohio State University Hospital
Columbus 4509177, Ohio 5165418, 43210-1257
Status
Address
Oregon Health and Science University
Portland 5746545, Oregon 5744337, 97201
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Address
University of Pennsylvania Hospital
Philadelphia 4560349, Pennsylvania 6254927, 19104
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Address
Thomas Jefferson University
Philadelphia 4560349, Pennsylvania 6254927, 19107
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Address
Sarah Cannon Research Institute SCRI
Nashville 4644585, Tennessee 4662168, 37203
Status
Address
Vanderbilt University Medical Center
Nashville 4644585, Tennessee 4662168, 37232-6303
Status
Address
University of Texas Southwestern Medical Center at Dallas
Dallas 4684888, Texas 4736286, 75390-9063
Status
Address
University of Texas MD Anderson Cancer Center
Houston 4699066, Texas 4736286, 77030
Status
Address
Huntsman Cancer Institute
Salt Lake City 5780993, Utah 5549030, 84112
Status
Address
USO-Virginia Cancer Specialists, PC
Fairfax 4758023, Virginia 6254928, 22031
Status
Address
University of Wisconsin-Madison Hospital and Health Clinic
Madison 5261457, Wisconsin 5279468, 53792
International Sites
Status
Address
Royal North Shore Hospital
St Leonards 8029783, New South Wales 2155400, 2065
Status
Address
Peter MacCallum Cancer Centre
Melbourne 2158177, Victoria 2145234, 3000
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Address
BC Cancer Vancouver
Vancouver 6173331, British Columbia 5909050, V5Z 4E6
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Address
Rigshospitalet
Copenhagen 2618425, , 2200
Status
Address
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
Bordeaux 3031582, Aquitaine, 33076
Status
Address
Centre Leon Berard
Lyon 2996944, Rhône-Alpes, 69008
Status
Address
APHM Hôpital de la Timone
Marseille 2995469, , 13385
Status
Address
Institut du Cancer de Montpellier - Val d'aurelle
Montpellier 2992166, , 34298
Status
Address
Gustave Roussy
Villejuif 2968705, , 94805
Status
Address
Hôpital Européen Georges Pompidou
Paris 2988507, Île-de-France Region 3012874, 75015
Status
Address
Universitätsklinikum Würzburg A. ö. R.
Würzburg 2805615, Bavaria 2951839, 97080
Status
Address
Universitätsklinikum Köln
Cologne 2886242, North Rhine-Westphalia 2861876, 50931
Status
Address
Prince of Wales Hospital
Hong Kong 1819729, Shatin, New Territories, 999077
Status
Address
Sheba Medical Center
Ramat Gan, Central District 294904, 5262100
Status
Address
Shaare Zedek Medical Center
Jerusalem 281184, Jerusalem 293198, 9103102
Status
Address
Soroka Medical Center - Pediatric Outpatient Clinic
Beersheba 295530, , 8410101
Status
Address
Hadassah Medical Center
Jerusalem 281184, , 9112001
Status
Address
Istituto Nazionale dei Tumori
Milan 3173435, Lombardy 3174618, 20133
Status
Address
Nagoya University Hospital
Nagoya 1856057, Aichi-ken 1865694, 466-8560
Status
Address
National Cancer Center Hospital East
Kashiwa 1859924, Chiba 2113014, 277-8577
Status
Address
Hokkaido University Hospital
Sapporo 2128295, Hokkaido 2130037, 060-8648
Status
Address
Hyogo Cancer Center
Akashi 1847966, Hyōgo 1862047, 673-8558
Status
Address
Kanazawa University Hospital
Kanazawa 1860243, Ishikawa-ken 1861387, 920-8641
Status
Address
Kindai University Hospital
Osaka Sayama-shi, Osaka 1853904, 589 8511
Status
Address
Tominaga Hospital
Nagaizumi-cho,Sunto-gun, Shizuoka 1851715, 411-8777
Status
Address
National Cancer Center Hospital
Chuo-ku, Tokyo 1850144, 104-0045
Status
Address
Japanese Foundation for Cancer Research
Koto, Tokyo 1850144, 135-8550
Status
Address
Tottori University Hospital
Yonago 1848277, Tottori 1849890, 683-8504
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Address
National Hospital Organization Kyushu Cancer Center
Fukuoka 1863967, , 811-1395
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Address
Okayama University Hospital
Okayama 1854383, , 700-8558
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Address
Osaka City General Hospital
Osaka 1853909, , 534-0021
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Address
National Cancer Centre Singapore
Singapore 1880252, Central Singapore, 169610
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Address
National Cancer Center
Goyang-si 1842485, Kyǒnggi-do, 10408
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Address
Seoul National University Bundang Hospital
Seongnam 6876792, Kyǒnggi-do, 13620
Status
Address
Severance Hospital, Yonsei University Health System
Seoul 1835848, Seoul-teukbyeolsi [Seoul], 03722
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Address
Asan Medical Center
Seoul 1835848, Seoul-teukbyeolsi [Seoul], 05505
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Address
Samsung Medical Center
Seoul 1835848, , 06351
Status
Address
Hospital Universitari Vall d'Hebron
Barcelona 3128760, Barcelona [Barcelona], 8035
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Address
Hospital Universitario Fundación Jiménez Díaz
Madrid 3117735, , 28040
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Address
Hospital Madrid Norte Sanchinarro
Madrid 3117735, , 28050
Status
Address
Kantonsspital Luzern
Lucerne 2659811, Canton of Lucerne 2659810, 6000
Status
Address
Taichung Veterans General Hospital
Taichung 1668399, , 40705
Status
Address
National Taiwan University Hospital
Taipei 1668341, , 10002
Status
Address
Royal Marsden Hospital
London 2643743, , SW3 6JJ
