Non-Small Cell Lung CancerPhase 1/2LIBRETTO-001NCT03157128
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)
A Phase 1/2 study testing LOXO-292 in people with Non-Small Cell Lung Cancer and Medullary Thyroid Cancer, run by Eli Lilly and Company at 85 sites in 16 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer, Medullary Thyroid Cancer, Colon Cancer
- What is being tested?
- LOXO-292
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 857 participants
- Where
- 85 sitesin 16 countries
- Study dates
- 2 May 2017to Feb 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
85 sites in 16 countries.
85 sites in 16 countries
United States41 sites
University of Michigan
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30329-5102
University of Maryland Medical Center
Baltimore, Maryland, 21201
Johns Hopkins University
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of North Carolina
Chapel Hill, North Carolina, 27514
University of Chicago Medicine-Comprehensive Cancer Center
Chicago, Illinois, 60637
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Ohio State University Hospital
Columbus, Ohio, 43210-1257
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390-9063
Sarah Cannon Research Institute at HealthOne
Denver, Colorado, 80218
City of Hope National Medical Center
Duarte, California, 91010-0269
USO-Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
START Midwest
Grand Rapids, Michigan, 49546
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic in Florida
Jacksonville, Florida, 32224
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
UCLA Medical Center
Los Angeles, California, 90095
University of Wisconsin-Madison Hospital and Health Clinic
Madison, Wisconsin, 53792
Sarah Cannon Research Institute SCRI
Nashville, Tennessee, 37203
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-6303
Yale Cancer Center
New Haven, Connecticut, 06520
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
NYU Langone
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
Kaiser Permanente
Oakland, California, 94611-5400
Irvine Medical Center
Orange, California, 92868
Memorial Hospital Pembroke
Pembroke, Florida, 33028
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Oregon Health and Science University
Portland, Oregon, 97201
Mayo Clinic
Rochester, Minnesota, 55905-0002
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
University of California - San Diego
San Diego, California, 92103
UCSF Medical Center at Mission Bay
San Francisco, California, 94158
Mayo Clinic of Scottsdale
Scottsdale, Arizona, 85259
Washington University Medical School
St Louis, Missouri, 63110
Kaiser Permanente Medical Center
Walnut Creek, California, 94596
Japan13 sites
Hyogo Cancer Center
Akashi, Hyōgo, 673-8558
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
National Hospital Organization Kyushu Cancer Center
Fukuoka, 811-1395
Kanazawa University Hospital
Kanazawa, Ishikawa-ken, 920-8641
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Japanese Foundation for Cancer Research
Koto, Tokyo, 135-8550
Tominaga Hospital
Nagaizumi-cho,Sunto-gun, Shizuoka, 411-8777
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8560
Okayama University Hospital
Okayama, 700-8558
Osaka City General Hospital
Osaka, 534-0021
Kindai University Hospital
Osaka Sayama-shi, Osaka, 589 8511
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648
Tottori University Hospital
Yonago, Tottori, 683-8504
France6 sites
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
Bordeaux, Aquitaine, 33076
Centre Leon Berard
Lyon, Auvergne-Rhône-Alpes, 69008
APHM Hôpital de la Timone
Marseille, 13385
Institut du Cancer de Montpellier - Val d'aurelle
Montpellier, 34298
Hôpital Européen Georges Pompidou
Paris, Île-de-France Region, 75015
Gustave Roussy
Villejuif, 94805
South Korea5 sites
National Cancer Center
Goyang-si, Kyǒnggi-do, 10408
Seoul National University Bundang Hospital
Seongnam, Kyǒnggi-do, 13620
Severance Hospital, Yonsei University Health System
Seoul, Seoul-teukbyeolsi [Seoul], 03722
Asan Medical Center
Seoul, Seoul-teukbyeolsi [Seoul], 05505
Samsung Medical Center
Seoul, 06351
Israel4 sites
Soroka Medical Center - Pediatric Outpatient Clinic
Beersheba, 8410101
Shaare Zedek Medical Center
Jerusalem, Jerusalem, 9103102
Hadassah Medical Center
Jerusalem, 9112001
Sheba Medical Center
Ramat Gan, Central District, 5262100
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [Barcelona], 8035
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Hospital Madrid Norte Sanchinarro
Madrid, 28050
Australia2 sites
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Germany2 sites
Universitätsklinikum Köln
Cologne, North Rhine-Westphalia, 50931
Universitätsklinikum Würzburg A. ö. R.
Würzburg, Bavaria, 97080
Taiwan2 sites
Taichung Veterans General Hospital
Taichung, 40705
National Taiwan University Hospital
Taipei, 10002
Hong Kong1 site
Prince of Wales Hospital
Hong Kong, Shatin, New Territories, 999077
Singapore1 site
National Cancer Centre Singapore
Singapore, Central Singapore, 169610
About this study
Official title: 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.
Read the 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)
- Being tested
- LOXO-292
- 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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Carcinoma, Medullary, Colonic Neoplasms, Neoplasms by Site, Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LOXO-292Drug
Also called Selpercatinib, LY3527723
Oral LOXO-292
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: 20 mg Selpercatinib QD | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 1: 20 mg Selpercatinib BID | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 1: 40 mg Selpercatinib BID | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 1: 60 mg Selpercatinib BID | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 1: 160 mg Selpercatinib QD | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 1: 80 mg Selpercatinib BID | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 1: 120 mg Selpercatinib BID | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 1: 160 mg Selpercatinib BID | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 1: 200 mg Selpercatinib BID | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 1: 240 mg Selpercatinib BID | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 2, Cohort 1: RET Fusion Solid Tumor | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 2, Cohort 2: RET Fusion Solid Tumor Without Standard Therapy | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 2, Cohort 3: RET Mutant MTC | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 2, Cohort 4: RET Mutant MTC Without Standard Therapy | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 2, Cohort 5: Advanced RET Altered Solid Tumor | Experimental | 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. Receives: Drug: LOXO-292 |
| Phase 2, Cohort 6: RET Inhibitor-Discontinued Participants | Experimental | 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. Receives: Drug: LOXO-292 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Maximum Tolerated Dose (MTD)
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.
Measured: Cycle 1 (cycle length = 28 days)
Phase 1: Recommended Phase 2 Dose (RP2D)
Phase 1: RP2D
Measured: Cycle 1 (cycle length = 28 days)
Phase 2: Objective Response Rate (ORR) Based on Independent Review Committee (IRC) Assessment
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.
Measured: Approximately for up to 7 years 8 months
Secondary outcomes (17)
Phase 1: Number of Participants With a Treatment-Related Adverse Event(s) (TRAE[s])
Phase 1: Number of Participants with a TRAE(s) is reported.
Measured: Up to 28 days
Phase 1: Number of Participants With an Abnormal Laboratory Values
Measured: Up to 28 days
Phase 2: Overall Response Rate (ORR) Based on RECIST 1.1 or RANO, as Appropriate to Tumor Type
Phase 2: ORR based on RECIST 1.1 or RANO, as Appropriate to Tumor Type
Measured: Approximately for up to 9 years 8 months
Phase 2: ORR (by Investigator)
Phase 2: ORR (by Investigator)
Measured: Approximately for up to 9 years 8 months
Phase 2: Best Change in Tumor Size From Baseline (by IRC and Investigator)
Phase 2: Best Change in Tumor Size from Baseline (by IRC and Investigator)
Measured: Approximately for up to 9 years 8 months
Phase 2: Duration of Response (DOR; by IRC and Investigator)
Phase 2: DOR (by IRC and Investigator)
Measured: Approximately for up to 9 years 8 months
Phase 2: Central Nervous System (CNS) ORR (by IRC)
Phase 2: CNS ORR (by IRC)
Measured: Approximately for up to 9 years 8 months
Phase 2: CNS DOR (by IRC)
Phase 2: CNS DOR (by IRC)
Measured: Approximately for up to 9 years 8 months
Phase 2: Time to Any and Best Response (by IRC and Investigator)
Phase 2: Time to Any and Best Response (by IRC and Investigator)
Measured: Approximately for up to 9 years 8 months
Phase 2: CBR (by IRC and Investigator)
Phase 2: CBR (by IRC and Investigator)
Measured: Approximately for up to 9 years 8 months
Phase 2: PFS (by IRC and Investigator)
Phase 2: PFS (by IRC and Investigator)
Measured: Approximately for up to 9 years 8 months
Phase 2: Overall Survival (OS)
Phase 2: OS
Measured: Approximately for up to 9 years 8 months
Phase 2: Percentage of Participants With Any Serious Adverse Event (SAE[s])
Phase 2: Percentage of Participants with any SAE(s)
Measured: Approximately for up to 9 years 8 months
Phase 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib)
Phase 2: PK: AUC of LOXO-292 (Selpercatinib)
Measured: Cycle 5 Day 1 (Cycle = 28 days)
Phase 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib)
Phase 2: PK: Cmax of LOXO-292 (Selpercatinib)
Measured: Cycle 5 Day 1 (Cycle = 28 days)
Phase 1: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours
Measured: 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)
Measured: Cycle 1 Day 8: Predose, 1, 2, 4, 8, 24 hours post dose (cycle length = 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2017
- Study start2 May 2017
- Primary completion14 Feb 2025
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 857 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Loxo Oncology, Inc.
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03157128
- Sponsor's protocol ID
- 17477
- Other IDs
- J2G-OX-JZJA, LOXO-RET-17001, 2017-000800-59, 2023-507702-13-00, 2023, 2017
- Acronym
- LIBRETTO-001
- Status last verified
- Mar 2026
- First submitted
- 9 May 2017
- Last updated
- 16 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
Gautschi O, Park K, Solomon BJ, Tomasini P, Loong HH, De Braud F, Goto K, Peterson P, Barker S, Liming K, Oxnard GR, Frimodt-Moller B, Drilon A. Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancer: Final Safety and Efficacy, Including Overall Survival, From the LIBRETTO-001 Phase I/II Trial. J Clin Oncol. 2025 May 20;43(15):1758-1764. doi: 10.1200/JCO-24-02076. Epub 2025 Feb 21.
PubMed 39983053Raez LE, Massey AC, Barker SS, Peterson PM, Liming K, Pennell NA. Long-term safety of selpercatinib for Rearranged during transfection (RET)-activated advanced solid tumors in LIBRETTO-001: differing patterns of adverse events over time. Oncologist. 2024 Dec 6;29(12):1068-1078. doi: 10.1093/oncolo/oyae282.
PubMed 39471424Wirth LJ, Brose MS, Subbiah V, Worden F, Solomon B, Robinson B, Hadoux J, Tomasini P, Weiler D, Deschler-Baier B, Tan DSW, Maeda P, Lin Y, Singh R, Bayt T, Drilon A, Cassier PA. Durability of Response With Selpercatinib in Patients With RET-Activated Thyroid Cancer: Long-Term Safety and Efficacy From LIBRETTO-001. J Clin Oncol. 2024 Sep 20;42(27):3187-3195. doi: 10.1200/JCO.23.02503. Epub 2024 Aug 2.
PubMed 39094065Deschler-Baier B, Krebs M, Kroiss M, Chatterjee M, Gundel D, Kestler C, Kerscher A, Kunzmann V, Appenzeller S, Maurus K, Rosenwald A, Bargou R, Gerhard-Hartmann E, Venkataramani V. Rapid response to selpercatinib in RET fusion positive pancreatic neuroendocrine carcinoma confirmed by smartwatch. NPJ Precis Oncol. 2024 Jul 31;8(1):167. doi: 10.1038/s41698-024-00659-x.
PubMed 39085487Deschler-Baier B, Konda B, Massarelli E, Hu MI, Wirth LJ, Xu X, Wright J, Clifton-Bligh RJ. Clinical Activity of Selpercatinib in RET-mutant Pheochromocytoma. J Clin Endocrinol Metab. 2025 Feb 18;110(3):e600-e606. doi: 10.1210/clinem/dgae283.
PubMed 38661071Subbiah V, Burris HA 3rd, Kurzrock R. Revolutionizing cancer drug development: Harnessing the potential of basket trials. Cancer. 2024 Jan;130(2):186-200. doi: 10.1002/cncr.35085. Epub 2023 Nov 7.
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