A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)

March 1, 2024 updated by: Loxo Oncology, Inc.

A Phase 1/2 Study of Oral Selpercatinib (LOXO-292) in Patients With Advanced Solid Tumors, Including RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors With RET Activation (LIBRETTO-001)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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)

Study Type

Interventional

Enrollment (Estimated)

875

Phase

  • Phase 2
  • Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
  • Phone Number: 1-317-615-4559
  • Email: ClinicalTrials.gov@Lilly.com

Study Locations

  • Australia
    • New South Wales
      • St. Leonards, New South Wales, Australia, 2065
        • Recruiting
        • Royal North Shore Hospital
        • Contact:
          • Phone Number: 61299267267
        • Principal Investigator:
          • bruce robinson
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Recruiting
        • Peter MacCallum Cancer Centre
        • Contact:
          • Phone Number: 61385595000
        • Principal Investigator:
          • Benjamin Solomon
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Recruiting
        • BC Cancer Vancouver
        • Contact:
          • Phone Number: 6048776000
        • Principal Investigator:
          • Janessa Laskin
  • Denmark
    • København Ø
      • Copenhagen, København Ø, Denmark, 2100
        • Recruiting
        • Rigshospitalet
        • Principal Investigator:
          • Kristoffer Rohrberg
        • Contact:
          • Phone Number: 004535456353
  • France
      • Bordeaux, France, 33076
        • Recruiting
        • Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
        • Contact:
          • Phone Number: 556333244
        • Principal Investigator:
          • Antoine Italiano
      • Lyon Cedex 08, France, 69373
        • Recruiting
        • Centre Léon Bérard
        • Contact:
          • Phone Number: 33426556833
        • Principal Investigator:
          • Philippe Cassier
      • Marseille, France, 13385
        • Recruiting
        • APHM Hôpital de la Timone
        • Contact:
          • Phone Number: 33491385918
        • Principal Investigator:
          • PASCALE TOMASINI
      • Montpellier Cedex 5, France, 34298
        • Not yet recruiting
        • Institut du Cancer de Montpellier - Val d'Aurelle
        • Contact:
          • Phone Number: 33467613100
        • Principal Investigator:
          • Diego Tosi
      • Villejuif Cedex, France, 94805
        • Recruiting
        • Gustave Roussy
        • Contact:
          • Phone Number: 33142114157
        • Principal Investigator:
          • Benjamin Besse
    • Cedex 15
      • Paris, Cedex 15, France, 75908
        • Recruiting
        • Hopital Europeen Georges Pompidou
        • Contact:
          • Phone Number: 33156093714
        • Principal Investigator:
          • Jacques Medioni
  • Germany
    • Bayern
      • Würzburg, Bayern, Germany, 97080
        • Recruiting
        • Universitätsklinikum Würzburg A. ö. R.
        • Contact:
          • Phone Number: 4993120139939
        • Principal Investigator:
          • Barbara Deschler-Baier
    • Nordrhein-Westfalen
      • Köln, Nordrhein-Westfalen, Germany, 50937
        • Recruiting
        • Universitätsklinikum Köln
        • Contact:
          • Phone Number: 492214783993
        • Principal Investigator:
          • Jürgen Wolf
  • Hong Kong
    • Shatin, New Territories
      • Hong Kong, Shatin, New Territories, Hong Kong
        • Recruiting
        • Prince of Wales Hospital
        • Contact:
          • Phone Number: 85226322648
        • Principal Investigator:
          • Herbert Loong
  • Israel
      • Beer-Sheva, Israel, 8410101
        • Recruiting
        • Soroka Medical Center - Pediatric Outpatient Clinic
        • Contact:
          • Phone Number: 972587040620
        • Principal Investigator:
          • Julia Dudnik
      • Jerusalem, Israel, 91120
        • Recruiting
        • Hadassah Medical Center
        • Principal Investigator:
          • Hovav Nechushtan
        • Contact:
          • Phone Number: 972508946057
    • Ramat Gan
      • Tel Hashomer, Ramat Gan, Israel, 5265601
        • Recruiting
        • Sheba Medical Center
        • Contact:
          • Phone Number: 972526667591
        • Principal Investigator:
          • Talia Golan
    • Yerushalayim
      • Jerusalem, Yerushalayim, Israel, 9103102
        • Not yet recruiting
        • Shaare Zedek Medical Center
        • Principal Investigator:
          • Nir Peled
  • Italy
    • Lombardie
      • Milano, Lombardie, Italy, 20133
        • Recruiting
        • Istituto Nazionale dei Tumori
        • Contact:
          • Phone Number: 390223902906
        • Principal Investigator:
          • Filippo De Braud
  • Japan
      • Fukuoka, Japan, 811-1395
        • Recruiting
        • National Hospital Organization Kyushu Cancer Center
        • Contact:
          • Phone Number: 81925413231
        • Principal Investigator:
          • Ryo Toyozawa
      • Okayama, Japan, 700-8558
        • Recruiting
        • Okayama University Hospital
        • Contact:
          • Phone Number: 81862237151
        • Principal Investigator:
          • Kadoaki Ohashi
      • Osaka, Japan, 534-0021
        • Recruiting
        • Osaka City General Hospital
        • Contact:
          • Phone Number: 81669291221
        • Principal Investigator:
          • Haruko Daga
    • Aichi
      • Nagoya, Aichi, Japan, 466-8560
        • Recruiting
        • Nagoya University Hospital
        • Contact:
          • Phone Number: 81527412111
        • Principal Investigator:
          • Masahiro Morise
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East
        • Contact:
          • Phone Number: 81471331111
        • Principal Investigator:
          • Koichi Goto
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
        • Recruiting
        • Hokkaido University Hospital
        • Contact:
          • Phone Number: 81 117161161
        • Principal Investigator:
          • Jun Sakakibara
    • Hyogo
      • Akashi, Hyogo, Japan, 673-8558
        • Recruiting
        • Hyogo Cancer Center
        • Contact:
          • Phone Number: 81789291151
        • Principal Investigator:
          • Miyako Satouchi
    • Ishikawa
      • Kanazawa, Ishikawa, Japan, 920-8641
        • Recruiting
        • Kanazawa University Hospital
        • Contact:
          • Phone Number: 81762652000
        • Principal Investigator:
          • Shinji Takeuchi
    • Osaka
      • Osaka Sayama-shi, Osaka, Japan, 589 8511
        • Recruiting
        • Kindai University Hospital
        • Contact:
          • Phone Number: 81723660221
        • Principal Investigator:
          • Tsutomu Iwasa
    • Shizuoka
      • Nagaizumi-cho,Sunto-gun, Shizuoka, Japan, 411-8777
        • Recruiting
        • Tominaga Hospital
        • Principal Investigator:
          • Hirotsugu Kenmotsu
        • Contact:
          • Phone Number: 81559895222
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital
        • Contact:
          • Phone Number: 81335422511
        • Principal Investigator:
          • YUICHIRO OHE
      • Koto, Tokyo, Japan, 135-8550
        • Recruiting
        • Japanese Foundation for Cancer Research
        • Contact:
          • Phone Number: 81335200111
        • Principal Investigator:
          • Makoto Nishio
    • Tottori
      • Yonago, Tottori, Japan, 683-8504
        • Recruiting
        • Tottori University Hospital
        • Contact:
          • Phone Number: 81859331111
        • Principal Investigator:
          • Tomohiro Sakamoto
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Severance Hospital, Yonsei University Health System
        • Contact:
          • Phone Number: 82222280880
        • Principal Investigator:
          • Byoung Chul Cho
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
        • Recruiting
        • National Cancer Center
        • Contact:
          • Phone Number: 82319201154
        • Principal Investigator:
          • Ji-Youn Han
    • Kyǒnggi-do
      • Seongnam, Kyǒnggi-do, Korea, Republic of, 13620
        • Recruiting
        • Seoul National University Bundang Hospital
        • Contact:
          • Phone Number: 82317877005
        • Principal Investigator:
          • Yu Jung Kim
    • Seoul-teukbyeolsi [Seoul]
      • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 05505
        • Recruiting
        • Asan Medical Center
        • Contact:
          • Phone Number: 8222243214
        • Principal Investigator:
          • Dae Ho Lee
      • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 06351
        • Recruiting
        • Samsung Medical Center
        • Principal Investigator:
          • Se Hoon Lee
        • Contact:
          • Phone Number: 82234102971
  • Singapore
      • Singapore, Singapore, 169610
        • Recruiting
        • National Cancer Centre Singapore
        • Contact:
          • Phone Number: 6564368000
        • Principal Investigator:
          • Shao Weng Daniel Tan
  • Spain
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Fundacion Jimenez Diaz
        • Principal Investigator:
          • Victor Moreno
        • Contact:
          • Phone Number: 34915504800
      • Madrid, Spain, 28050
        • Recruiting
        • Hospital Madrid Norte Sanchinarro
        • Contact:
          • Phone Number: 917567800
        • Principal Investigator:
          • Maria Jose de Miguel Luken
    • Barcelona [Barcelona]
      • Barcelona, Barcelona [Barcelona], Spain, 8035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Contact:
          • Phone Number: 934893000
        • Principal Investigator:
          • Elena Garralda Cabanas
  • Switzerland
    • Luzern
      • Luzern 16, Luzern, Switzerland, 6000
        • Recruiting
        • Kantonsspital Luzern
        • Contact:
          • Phone Number: 0041412055964
        • Principal Investigator:
          • Oliver Gautschi
  • Taiwan
      • Taichung, Taiwan, 40705, ROC
        • Recruiting
        • Taichung Veterans General Hospital
        • Principal Investigator:
          • Kuo-Hsuan Hsu
        • Contact:
          • Phone Number: 886423592525
      • Taipei, Taiwan, 10002
        • Recruiting
        • National Taiwan University Hospital
        • Principal Investigator:
          • Chih-Hsin Yang
        • Contact:
          • Phone Number: 8862231245665339
  • United Kingdom
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Recruiting
        • Royal Marsden Hospital
        • Contact:
          • Phone Number: 02086426011
        • Principal Investigator:
          • Anna Minchom
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic of Scottsdale
        • Contact:
          • Phone Number: 480-301-8000
        • Principal Investigator:
          • Nina Karlin
    • California
      • Duarte, California, United States, 91010-0269
        • Recruiting
        • City of Hope National Medical Center
        • Contact:
          • Phone Number: 818-359-8111
        • Principal Investigator:
          • Erminia Massarelli
      • La Jolla, California, United States, 92161
        • Recruiting
        • University of California - San Diego
        • Contact:
          • Phone Number: 858-822-6189
        • Principal Investigator:
          • Lyudmila Bazhenova
      • Los Angeles, California, United States, 90095
        • Recruiting
        • UCLA Medical Center
        • Contact:
          • Phone Number: 310-794-1816
        • Principal Investigator:
          • Jonathan Goldman
      • Newport Beach, California, United States, 92663
        • Not yet recruiting
        • Hoag Memorial Hospital Presbyterian
        • Contact:
          • Phone Number: 949-761-6767
        • Principal Investigator:
          • Michael Demeure
      • Orange, California, United States, 92868
        • Recruiting
        • Irvine Medical Center
        • Contact:
          • Phone Number: 714-456-8105
        • Principal Investigator:
          • Misako Nagasaka
      • San Francisco, California, United States, 94115
        • Recruiting
        • UCSF Medical Center at Mission Bay
        • Contact:
          • Phone Number: 415-885-3882
        • Principal Investigator:
          • Hyunseok Kang
      • Santa Clara, California, United States, 95051
        • Recruiting
        • Kaiser Permanente
        • Contact:
          • Phone Number: 708-851-9588
        • Principal Investigator:
          • Minggui Pan
      • Vallejo, California, United States, 94589
        • Recruiting
        • Kaiser Permanente Medical Center
        • Contact:
          • Phone Number: 510-891-3414
        • Principal Investigator:
          • Jennifer Suga
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Sarah Cannon Research Institute at HealthONE
        • Principal Investigator:
          • Gerald Falchook
        • Contact:
          • Phone Number: 720-754-2610
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale Cancer Center
        • Contact:
          • Phone Number: 203-737-5234
        • Principal Investigator:
          • Frederick Wilson
    • District of Columbia
      • Washington, District of Columbia, United States, 20016
        • Recruiting
        • Johns Hopkins University
        • Principal Investigator:
          • Benjamin Levy
        • Contact:
          • Phone Number: 202-660-6500
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic in Florida
        • Contact:
          • Phone Number: 904-953-2224
        • Principal Investigator:
          • Victor Bernet
      • Pembroke, Florida, United States, 33028
        • Recruiting
        • Memorial Hospital Pembroke
        • Contact:
          • Phone Number: 954-265-4325
        • Principal Investigator:
          • Luis Raez
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University
        • Principal Investigator:
          • Conor Steuer
        • Contact:
          • Phone Number: 440-778-1900
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Medicine-Comprehensive Cancer Center
        • Principal Investigator:
          • Christine Bestvina
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Recruiting
        • Ochsner Clinic Foundation
        • Contact:
          • Phone Number: 504-842-3910
        • Principal Investigator:
          • Marc Matrana
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland Medical Center
        • Contact:
          • Phone Number: 410-328-8708
        • Principal Investigator:
          • Ranee Mehra
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
          • Phone Number: 617-726-2000
        • Principal Investigator:
          • Lori Wirth
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • Jacob Sands
        • Contact:
          • Phone Number: 617-632-5960
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Contact:
          • Phone Number: 734-764-1817
        • Principal Investigator:
          • Francis Worden
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • START Midwest
        • Contact:
          • Phone Number: 616-954-5554
        • Principal Investigator:
          • Nehal Lakhani
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
        • Contact:
          • Phone Number: 5072844080
        • Principal Investigator:
          • John Columbus Morris
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University Medical School
        • Principal Investigator:
          • Saiama Waqar
        • Contact:
          • Phone Number: 314-362-7229
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Not yet recruiting
        • Comprehensive Cancer Centers of Nevada
        • Contact:
          • Phone Number: 702-952-3400
        • Principal Investigator:
          • Fadi Braiteh
    • New York
      • Buffalo, New York, United States, 14263-0002
        • Recruiting
        • Roswell Park Cancer Institute
        • Contact:
          • Phone Number: 716-845-3099
        • Principal Investigator:
          • Grace Dy
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Phone Number: 646-888-4206
        • Principal Investigator:
          • Alexander Drilon
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone
        • Principal Investigator:
          • Vamsidhar Velcheti
        • Contact:
          • Phone Number: 212-731-5662
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7305
        • Recruiting
        • University of North Carolina
        • Contact:
          • Phone Number: 866-869-1856
        • Principal Investigator:
          • Jared Weiss
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic Foundation
        • Contact:
          • Phone Number: 216-444-1128
        • Principal Investigator:
          • Nathan Pennell
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Hospital
        • Contact:
          • Phone Number: 614-293-4680
        • Principal Investigator:
          • Vineeth Sukrithan
    • Oregon
      • Portland, Oregon, United States, 97201
        • Recruiting
        • Oregon Health and Science University
        • Contact:
          • Phone Number: 503-494-8534
        • Principal Investigator:
          • Shivaani Kummar
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University
        • Principal Investigator:
          • Marcia Brose
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania Hospital
        • Principal Investigator:
          • Devraj Basu
        • Contact:
          • Phone Number: 215-746-6344
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6307
        • Recruiting
        • Vanderbilt University Medical Center
        • Contact:
          • Phone Number: 615-936-8580
        • Principal Investigator:
          • Jordan Berlin
    • Texas
      • Dallas, Texas, United States, 75390-9063
        • Recruiting
        • University of Texas Southwestern Medical Center at Dallas
        • Principal Investigator:
          • Tian Zhang
        • Contact:
          • Phone Number: 214-648-4180
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas MD Anderson Cancer Center
        • Contact:
          • Phone Number: 713-745-6754
        • Principal Investigator:
          • Vivek Subbiah
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute
        • Contact:
          • Phone Number: 801-585-5986
        • Principal Investigator:
          • Wallace Akerley
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • USO-Virginia Cancer Specialists, PC
        • Principal Investigator:
          • Alexander Spira
        • Contact:
          • Phone Number: 703-280-5390
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin-Madison Hospital and Health Clinic
        • Contact:
          • Phone Number: 608-262-2803
        • Principal Investigator:
          • Mark Burkard

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LOXO-292
Phase 1 - Multiple doses of LOXO-292 (selpercatinib) Phase 2 - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: MTD
Time Frame: The first 28 days of treatment (Cycle 1)
Incidence rate and category of dose limiting toxicities (DLTs) during the first 28-day cycle of LOXO-292 (selpercatinib) treatment
The first 28 days of treatment (Cycle 1)
Phase 1: RP2D
Time Frame: The first 28 days of treatment (Cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the participant discontinues from the study)
Phase 1: RP2D
The first 28 days of treatment (Cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the participant discontinues from the study)
Phase 2: Objective Response Rate
Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.
As assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Response Assessment in Neuro-Oncology (RANO), as appropriate to tumor type, as assessed by independent review committee (IRC)
Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Number of Participants with a Treatment-Related Adverse Event(s) (TRAE[s])
Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Phase 1: Number of Participants with a TRAE(s)
From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Phase 1: Number of Participants with an Abnormal Laboratory or Physical Exam Result(s)
Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Phase 1: Number of Participants with an Abnormal Laboratory or Physical Exam Result(s)
From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Phase 1: Overall Response Rate (ORR) based on RECIST 1.1 or RANO, as Appropriate to Tumor Type
Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 1: ORR based on RECIST 1.1 or RANO, as Appropriate to Tumor Type
Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: ORR (by Investigator)
Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: ORR (by Investigator)
Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: Best Change in Tumor Size from Baseline (by IRC and Investigator)
Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: Best Change in Tumor Size from Baseline (by IRC and Investigator)
Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: Duration of Response (DOR; by IRC and Investigator)
Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: DOR (by IRC and Investigator)
Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: Central Nervous System (CNS) ORR (by IRC)
Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: CNS ORR (by IRC)
Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: CNS DOR (by IRC)
Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: CNS DOR (by IRC)
Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: Time to Any and Best Response (by IRC and Investigator)
Time Frame: every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: Time to Any and Best Response (by IRC and Investigator)
every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: CBR (by IRC and Investigator)
Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: CBR (by IRC and Investigator)
Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: PFS (by IRC and Investigator)
Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: PFS (by IRC and Investigator)
Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: Overall Survival (OS)
Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: OS
Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed
Phase 2: Percentage of Participants with any Serious Adverse Event (SAE[s])
Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Phase 2: Percentage of Participants with any SAE(s)
From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Phase 1 and 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib)
Time Frame: Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 28 days)
Phase 1 and 2: PK: AUC of LOXO-292 (Selpercatinib)
Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 28 days)
Phase 1 and 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib)
Time Frame: Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 28 days)
Phase 1 and 2: PK: Cmax of LOXO-292 (Selpercatinib)
Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loxo Oncology, Inc.

Collaborators

Eli Lilly and Company

Investigators

  • Study Director: 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), Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2017

Primary Completion (Estimated)

February 28, 2025

Study Completion (Estimated)

February 28, 2026

Study Registration Dates

First Submitted

May 9, 2017

First Submitted That Met QC Criteria

May 15, 2017

First Posted (Actual)

May 17, 2017

Study Record Updates

Last Update Posted (Actual)

March 4, 2024

Last Update Submitted That Met QC Criteria

March 1, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17477
  • J2G-OX-JZJA (Other Identifier: Eli Lilly and Company)
  • LOXO-RET-17001 (Other Identifier: Loxo Oncology, Inc.)
  • 2017-000800-59 (EudraCT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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