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 27, 2026 updated by: Eli Lilly and Company

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

Active, not 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 six 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)

Study Type

Interventional

Enrollment (Actual)

857

Phase

  • Phase 2
  • Phase 1

Expanded Access

Approved for sale to the public. 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 Locations

  • Australia
    • New South Wales
      • St Leonards, New South Wales, Australia, 2065
        • Royal North Shore Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Peter Maccallum Cancer Centre
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer Vancouver
  • Denmark
      • Copenhagen, Denmark, 2200
        • Rigshospitalet
  • France
      • Marseille, France, 13385
        • APHM Hopital de la Timone
      • Montpellier, France, 34298
        • Institut du Cancer de Montpellier - Val d'aurelle
      • Villejuif, France, 94805
        • Gustave Roussy
    • Aquitaine
      • Bordeaux, Aquitaine, France, 33076
        • Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
    • Auvergne-Rhône-Alpes
      • Lyon, Auvergne-Rhône-Alpes, France, 69008
        • Centre Leon Berard
    • Île-de-France Region
      • Paris, Île-de-France Region, France, 75015
        • Hôpital Europeen Georges Pompidou
  • Germany
    • Bavaria
      • Würzburg, Bavaria, Germany, 97080
        • Universitätsklinikum Würzburg A. ö. R.
    • North Rhine-Westphalia
      • Cologne, North Rhine-Westphalia, Germany, 50931
        • Universitätsklinikum Köln
  • Hong Kong
    • Shatin, New Territories
      • Hong Kong, Shatin, New Territories, Hong Kong, 999077
        • Prince of Wales Hospital
  • Israel
      • Beersheba, Israel, 8410101
        • Soroka Medical Center - Pediatric Outpatient Clinic
      • Jerusalem, Israel, 9112001
        • Hadassah Medical Center
    • Central District
      • Ramat Gan, Central District, Israel, 5262100
        • Sheba Medical Center
    • Jerusalem
      • Jerusalem, Jerusalem, Israel, 9103102
        • Shaare Zedek Medical Center
  • Italy
    • Lombardy
      • Milan, Lombardy, Italy, 20133
        • Istituto Nazionale dei Tumori
  • Japan
      • Fukuoka, Japan, 811-1395
        • National Hospital Organization Kyushu Cancer Center
      • Okayama, Japan, 700-8558
        • Okayama University Hospital
      • Osaka, Japan, 534-0021
        • Osaka City General Hospital
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 466-8560
        • Nagoya University Hospital
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
        • Hokkaido University Hospital
    • Hyōgo
      • Akashi, Hyōgo, Japan, 673-8558
        • Hyogo Cancer Center
    • Ishikawa-ken
      • Kanazawa, Ishikawa-ken, Japan, 920-8641
        • Kanazawa University Hospital
    • Osaka
      • Osaka Sayama-shi, Osaka, Japan, 589 8511
        • Kindai University Hospital
    • Shizuoka
      • Nagaizumi-cho,Sunto-gun, Shizuoka, Japan, 411-8777
        • Tominaga Hospital
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
      • Koto, Tokyo, Japan, 135-8550
        • Japanese Foundation for Cancer Research
    • Tottori
      • Yonago, Tottori, Japan, 683-8504
        • Tottori University Hospital
  • Singapore
    • Central Singapore
      • Singapore, Central Singapore, Singapore, 169610
        • National Cancer Centre Singapore
  • South Korea
      • Seoul, South Korea, 06351
        • Samsung Medical Center
    • Kyǒnggi-do
      • Goyang-si, Kyǒnggi-do, South Korea, 10408
        • National Cancer Center
      • Seongnam, Kyǒnggi-do, South Korea, 13620
        • Seoul National University Bundang Hospital
    • Seoul-teukbyeolsi [Seoul]
      • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 05505
        • Asan Medical Center
  • Spain
      • Madrid, Spain, 28040
        • Hospital Universitario Fundacion Jimenez Diaz
      • Madrid, Spain, 28050
        • Hospital Madrid Norte Sanchinarro
    • Barcelona [Barcelona]
      • Barcelona, Barcelona [Barcelona], Spain, 8035
        • Hospital Universitari Vall d'Hebron
  • Switzerland
    • Canton of Lucerne
      • Lucerne, Canton of Lucerne, Switzerland, 6000
        • Kantonsspital Luzern
  • Taiwan
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
  • United Kingdom
      • London, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic of Scottsdale
    • California
      • Duarte, California, United States, 91010-0269
        • City of Hope National Medical Center
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • Newport Beach, California, United States, 92663
        • Hoag Memorial Hospital Presbyterian
      • Oakland, California, United States, 94611-5400
        • Kaiser Permanente
      • Orange, California, United States, 92868
        • Irvine Medical Center
      • San Diego, California, United States, 92103
        • University of California - San Diego
      • San Francisco, California, United States, 94158
        • UCSF Medical Center at Mission Bay
      • Walnut Creek, California, United States, 94596
        • Kaiser Permanente Medical Center
    • Colorado
      • Denver, Colorado, United States, 80218
        • Sarah Cannon Research Institute at HealthONE
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale Cancer Center
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic in Florida
      • Pembroke, Florida, United States, 33028
        • Memorial Hospital Pembroke
    • Georgia
      • Atlanta, Georgia, United States, 30329-5102
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medicine-Comprehensive Cancer Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical 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
      • Grand Rapids, Michigan, United States, 49546
        • START Midwest
    • Minnesota
      • Rochester, Minnesota, United States, 55905-0002
        • Mayo Clinic
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University Medical School
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • NYU Langone
    • 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
    • Oregon
      • Portland, Oregon, United States, 97201
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute SCRI
      • Nashville, Tennessee, United States, 37232-6303
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75390-9063
        • University Of Texas Southwestern Medical Center At Dallas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • USO-Virginia Cancer Specialists, PC
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin-Madison Hospital and Health Clinic

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: Phase 1: 20 mg Selpercatinib QD
Participants received Selpercatinib 20 milligrams (mg) administered orally once daily (QD), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 1: 20 mg Selpercatinib BID
Participants received Selpercatinib 20 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 1: 40 mg Selpercatinib BID
Participants received Selpercatinib 40 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 1: 60 mg Selpercatinib BID
Participants received Selpercatinib 60 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 1: 160 mg Selpercatinib QD
Participants received Selpercatinib 160 milligrams (mg) administered orally once daily (QD), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 1: 80 mg Selpercatinib BID
Participants received Selpercatinib 80 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 1: 120 mg Selpercatinib BID
Participants received Selpercatinib 120 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 1: 160 mg Selpercatinib BID
Participants received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 1: 200 mg Selpercatinib BID
Participants received Selpercatinib 200 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 1: 240 mg Selpercatinib BID
Participants received Selpercatinib 240 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 2, Cohort 1: RET Fusion Solid Tumor
Participants with Rearranged during transfection (RET) Fusion solid tumor progressed on/intolerant to standard first line therapy received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 2, Cohort 2: RET Fusion Solid Tumor Without Standard Therapy
Participants with RET Fusion solid tumor without standard first line therapy received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 2, Cohort 3: RET Mutant MTC
Participants with RET mutant medullary thyroid cancer (MTC) progressed on/intolerant to standard first line therapy received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 2, Cohort 4: RET Mutant MTC Without Standard Therapy
Participants with RET mutant MTC without prior standard first line therapy or other kinase inhibitor(s) with anti-RET activity received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 2, Cohort 5: Advanced RET Altered Solid Tumor
Participants with RET altered solid tumor (cohorts 1-4, disease not measurable; MTC not eligible for Cohort 3 or 4; MTC syndrome spectrum cancer; circulating free tumor DNA [cfDNA+] for RET alteration not known to be present in tumor) received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Drug: LOXO-292
Oral LOXO-292
Other Names:
  • LY3527723
  • Selpercatinib
Experimental: Phase 2, Cohort 6: RET Inhibitor-Discontinued Participants
Participants otherwise eligible for Cohorts 1-5 who discontinued other RET inhibitors received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
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: Maximum Tolerated Dose (MTD)
Time Frame: Cycle 1 (cycle length = 28 days)

The MTD is defined as the highest dose level at which none of the first 3 treated patients, or not more than 1 of the first 6 treated patients, experiences a DLT. A DLT is any adverse events that starts on or after first administration of study drug, as defined by National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.

  • Any Grade(G) ≥3 nonhematologic toxicity, excluding
  • G3 AST, ALT, and/or total bilirubin elevation for <7 days.
  • G3 neutropenia <7 days
  • G3 thrombocytopenia without clinically significant bleeding
  • G3 or G4 lymphopenia.
  • First occurrence of G3 or G4 electrolyte abnormalities
  • G3 fatigue, weakness, nausea; other manageable constitutional symptom
  • G3 or G4 vomiting or diarrhea that lasts for <48hours with antiemetic/antidiarrheal medication in case of G3 and <24 hours in case of G4
  • G4 manageable constitutional symptom.
Cycle 1 (cycle length = 28 days)
Phase 1: Recommended Phase 2 Dose (RP2D)
Time Frame: Cycle 1 (cycle length = 28 days)
Phase 1: RP2D
Cycle 1 (cycle length = 28 days)
Phase 2: Objective Response Rate (ORR) Based on Independent Review Committee (IRC) Assessment
Time Frame: Approximately for up to 7 years 8 months

Objective Response Rate was defined as the percentage of participants with best overall response of confirmed response (CR), or Partial response (PR). Response was confirmed by a repeat assessment no less than 28 days.

  • CR is defined as disappearance of all target lesions.
  • PR is defined as at least a 30% decrease in the sum of diameter (LD for non-nodal lesions and short axis diameter [SAD] for nodal lesions) of target lesions, taking as reference the baseline sum LD.

ORR was assessed by independent review committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 95% confidence interval was calculated using Clopper-Pearson method.
Approximately for up to 7 years 8 months

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: Up to 28 days
Phase 1: Number of Participants with a TRAE(s) is reported.
Up to 28 days
Phase 1: Number of Participants With an Abnormal Laboratory Values
Time Frame: Up to 28 days
Up to 28 days
Phase 2: Overall Response Rate (ORR) Based on RECIST 1.1 or RANO, as Appropriate to Tumor Type
Time Frame: Approximately for up to 9 years 8 months
Phase 2: ORR based on RECIST 1.1 or RANO, as Appropriate to Tumor Type
Approximately for up to 9 years 8 months
Phase 2: ORR (by Investigator)
Time Frame: Approximately for up to 9 years 8 months
Phase 2: ORR (by Investigator)
Approximately for up to 9 years 8 months
Phase 2: Best Change in Tumor Size From Baseline (by IRC and Investigator)
Time Frame: Approximately for up to 9 years 8 months
Phase 2: Best Change in Tumor Size from Baseline (by IRC and Investigator)
Approximately for up to 9 years 8 months
Phase 2: Duration of Response (DOR; by IRC and Investigator)
Time Frame: Approximately for up to 9 years 8 months
Phase 2: DOR (by IRC and Investigator)
Approximately for up to 9 years 8 months
Phase 2: Central Nervous System (CNS) ORR (by IRC)
Time Frame: Approximately for up to 9 years 8 months
Phase 2: CNS ORR (by IRC)
Approximately for up to 9 years 8 months
Phase 2: CNS DOR (by IRC)
Time Frame: Approximately for up to 9 years 8 months
Phase 2: CNS DOR (by IRC)
Approximately for up to 9 years 8 months
Phase 2: Time to Any and Best Response (by IRC and Investigator)
Time Frame: Approximately for up to 9 years 8 months
Phase 2: Time to Any and Best Response (by IRC and Investigator)
Approximately for up to 9 years 8 months
Phase 2: CBR (by IRC and Investigator)
Time Frame: Approximately for up to 9 years 8 months
Phase 2: CBR (by IRC and Investigator)
Approximately for up to 9 years 8 months
Phase 2: PFS (by IRC and Investigator)
Time Frame: Approximately for up to 9 years 8 months
Phase 2: PFS (by IRC and Investigator)
Approximately for up to 9 years 8 months
Phase 2: Overall Survival (OS)
Time Frame: Approximately for up to 9 years 8 months
Phase 2: OS
Approximately for up to 9 years 8 months
Phase 2: Percentage of Participants With Any Serious Adverse Event (SAE[s])
Time Frame: Approximately for up to 9 years 8 months
Phase 2: Percentage of Participants with any SAE(s)
Approximately for up to 9 years 8 months
Phase 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib)
Time Frame: Cycle 5 Day 1 (Cycle = 28 days)
Phase 2: PK: AUC of LOXO-292 (Selpercatinib)
Cycle 5 Day 1 (Cycle = 28 days)
Phase 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib)
Time Frame: Cycle 5 Day 1 (Cycle = 28 days)
Phase 2: PK: Cmax of LOXO-292 (Selpercatinib)
Cycle 5 Day 1 (Cycle = 28 days)
Phase 1: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours
Time Frame: Cycle 1 Day 8: Predose, 1, 2, 4, 8, 24 hours post dose (cycle length = 28 days)
Cycle 1 Day 8: Predose, 1, 2, 4, 8, 24 hours post dose (cycle length = 28 days)
Phase 1: Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax)
Time Frame: Cycle 1 Day 8: Predose, 1, 2, 4, 8, 24 hours post dose (cycle length = 28 days)
Cycle 1 Day 8: Predose, 1, 2, 4, 8, 24 hours post dose (cycle length = 28 days)

Collaborators and Investigators

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

Sponsor

Eli Lilly and Company

Collaborators

Loxo Oncology, Inc.

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 (Actual)

February 14, 2025

Study Completion (Estimated)

February 1, 2027

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)

April 16, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

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)
  • 2023-507702-13-00 (Ctis)

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.

Clinical Trials on Non-Small Cell Lung Cancer

Clinical Trials on LOXO-292

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Panama

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe