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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03157128




Registration number
Help: Registration number
NCT03157128
Ethics application status
Help: Ethics application status
Date submitted
Help: Date submitted
9/05/2017
Date registered
Help: Date registered
17/05/2017
Date last updated
Help: Date last updated
16/04/2026

Titles & IDs
Public title
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)
Scientific 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)
Additional trial identifiers [1] 0 0
J2G-OX-JZJA
Additional trial identifiers [2] 0 0
17477
Universal Trial Number (UTN)
Trial acronym
LIBRETTO-001
Related trial records

Health condition
Health condition(s) studied:
Non-Small Cell Lung Cancer 0 0
Medullary Thyroid Cancer 0 0
Colon Cancer 0 0
Any Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Any cancer
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Small cell
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Thyroid
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional(has expanded access)
Description of the intervention or exposure
Treatment: Drugs - LOXO-292

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.


Treatment: Drugs: LOXO-292
Oral LOXO-292
Intervention code [1] 0 0
Treatment: Drugs
Description of the comparator or control
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Maximum Tolerated Dose (MTD)
Timepoint [1] 0 0
Cycle 1 (cycle length = 28 days)
Primary outcome [2] 0 0
Phase 1: Recommended Phase 2 Dose (RP2D)
Timepoint [2] 0 0
Cycle 1 (cycle length = 28 days)
Primary outcome [3] 0 0
Phase 2: Objective Response Rate (ORR) Based on Independent Review Committee (IRC) Assessment
Timepoint [3] 0 0
Approximately for up to 7 years 8 months
Secondary outcome [1] 0 0
Phase 1: Number of Participants With a Treatment-Related Adverse Event(s) (TRAE[s])
Timepoint [1] 0 0
Up to 28 days
Secondary outcome [2] 0 0
Phase 1: Number of Participants With an Abnormal Laboratory Values
Timepoint [2] 0 0
Up to 28 days
Secondary outcome [3] 0 0
Phase 2: Overall Response Rate (ORR) Based on RECIST 1.1 or RANO, as Appropriate to Tumor Type
Timepoint [3] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [4] 0 0
Phase 2: ORR (by Investigator)
Timepoint [4] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [5] 0 0
Phase 2: Best Change in Tumor Size From Baseline (by IRC and Investigator)
Timepoint [5] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [6] 0 0
Phase 2: Duration of Response (DOR; by IRC and Investigator)
Timepoint [6] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [7] 0 0
Phase 2: Central Nervous System (CNS) ORR (by IRC)
Timepoint [7] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [8] 0 0
Phase 2: CNS DOR (by IRC)
Timepoint [8] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [9] 0 0
Phase 2: Time to Any and Best Response (by IRC and Investigator)
Timepoint [9] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [10] 0 0
Phase 2: CBR (by IRC and Investigator)
Timepoint [10] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [11] 0 0
Phase 2: PFS (by IRC and Investigator)
Timepoint [11] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [12] 0 0
Phase 2: Overall Survival (OS)
Timepoint [12] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [13] 0 0
Phase 2: Percentage of Participants With Any Serious Adverse Event (SAE[s])
Timepoint [13] 0 0
Approximately for up to 9 years 8 months
Secondary outcome [14] 0 0
Phase 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib)
Timepoint [14] 0 0
Cycle 5 Day 1 (Cycle = 28 days)
Secondary outcome [15] 0 0
Phase 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib)
Timepoint [15] 0 0
Cycle 5 Day 1 (Cycle = 28 days)
Secondary outcome [16] 0 0
Phase 1: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours
Timepoint [16] 0 0
Cycle 1 Day 8: Predose, 1, 2, 4, 8, 24 hours post dose (cycle length = 28 days)
Secondary outcome [17] 0 0
Phase 1: Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax)
Timepoint [17] 0 0
Cycle 1 Day 8: Predose, 1, 2, 4, 8, 24 hours post dose (cycle length = 28 days)

Eligibility
Key inclusion criteria
Key

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
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
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 design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/05/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/02/2027
Actual
Sample size
Target
Accrual to date
Final
857
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oregon
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Wisconsin
Country [25] 0 0
Canada
State/province [25] 0 0
British Columbia
Country [26] 0 0
Denmark
State/province [26] 0 0
Copenhagen
Country [27] 0 0
France
State/province [27] 0 0
Aquitaine
Country [28] 0 0
France
State/province [28] 0 0
Auvergne-Rhône-Alpes
Country [29] 0 0
France
State/province [29] 0 0
Marseille
Country [30] 0 0
France
State/province [30] 0 0
Montpellier
Country [31] 0 0
France
State/province [31] 0 0
Villejuif
Country [32] 0 0
France
State/province [32] 0 0
Île-de-France Region
Country [33] 0 0
Germany
State/province [33] 0 0
Bavaria
Country [34] 0 0
Germany
State/province [34] 0 0
North Rhine-Westphalia
Country [35] 0 0
Hong Kong
State/province [35] 0 0
Shatin, New Territories
Country [36] 0 0
Israel
State/province [36] 0 0
Central District
Country [37] 0 0
Israel
State/province [37] 0 0
Jerusalem
Country [38] 0 0
Israel
State/province [38] 0 0
Beersheba
Country [39] 0 0
Italy
State/province [39] 0 0
Lombardy
Country [40] 0 0
Japan
State/province [40] 0 0
Aichi-ken
Country [41] 0 0
Japan
State/province [41] 0 0
Chiba
Country [42] 0 0
Japan
State/province [42] 0 0
Hokkaido
Country [43] 0 0
Japan
State/province [43] 0 0
Hyogo
Country [44] 0 0
Japan
State/province [44] 0 0
Ishikawa-ken
Country [45] 0 0
Japan
State/province [45] 0 0
Osaka
Country [46] 0 0
Japan
State/province [46] 0 0
Shizuoka
Country [47] 0 0
Japan
State/province [47] 0 0
Tokyo
Country [48] 0 0
Japan
State/province [48] 0 0
Tottori
Country [49] 0 0
Japan
State/province [49] 0 0
Fukuoka
Country [50] 0 0
Japan
State/province [50] 0 0
Okayama
Country [51] 0 0
Singapore
State/province [51] 0 0
Central Singapore
Country [52] 0 0
South Korea
State/province [52] 0 0
Kyonggi-do
Country [53] 0 0
South Korea
State/province [53] 0 0
Seoul-teukbyeolsi [Seoul]
Country [54] 0 0
South Korea
State/province [54] 0 0
Seoul
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona [Barcelona]
Country [56] 0 0
Spain
State/province [56] 0 0
Madrid
Country [57] 0 0
Switzerland
State/province [57] 0 0
Canton of Lucerne
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taichung
Country [59] 0 0
Taiwan
State/province [59] 0 0
Taipei
Country [60] 0 0
United Kingdom
State/province [60] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Loxo Oncology, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
Address 0 0
Country 0 0
Phone 0 0
1-317-615-4559
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03157128