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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03157128




Registration number
NCT03157128
Ethics application status
Date submitted
9/05/2017
Date registered
17/05/2017
Date last updated
4/03/2024

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)
Secondary ID [1] 0 0
J2G-OX-JZJA
Secondary ID [2] 0 0
17477
Universal Trial Number (UTN)
Trial acronym
LIBRETTO-001
Linked study record

Health condition
Health condition(s) or problem(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 - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Thyroid
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

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

Experimental: LOXO-292 - Phase 1 - Multiple doses of LOXO-292 (selpercatinib) Phase 2 - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)


Treatment: Drugs: LOXO-292
Oral LOXO-292
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: MTD
Timepoint [1] 0 0
The first 28 days of treatment (Cycle 1)
Primary outcome [2] 0 0
Phase 1: RP2D
Timepoint [2] 0 0
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)
Primary outcome [3] 0 0
Phase 2: Objective Response Rate
Timepoint [3] 0 0
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 [1] 0 0
Phase 1: Number of Participants with a Treatment-Related Adverse Event(s) (TRAE[s])
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Phase 1: Number of Participants with an Abnormal Laboratory or Physical Exam Result(s)
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Phase 1: Overall Response Rate (ORR) based on RECIST 1.1 or RANO, as Appropriate to Tumor Type
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Phase 2: ORR (by Investigator)
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Phase 2: Best Change in Tumor Size from Baseline (by IRC and Investigator)
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Phase 2: Duration of Response (DOR; by IRC and Investigator)
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Phase 2: Central Nervous System (CNS) ORR (by IRC)
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
Phase 2: CNS DOR (by IRC)
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
Phase 2: Time to Any and Best Response (by IRC and Investigator)
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
Phase 2: CBR (by IRC and Investigator)
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
Phase 2: PFS (by IRC and Investigator)
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
Phase 2: Overall Survival (OS)
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Phase 2: Percentage of Participants with any Serious Adverse Event (SAE[s])
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Phase 1 and 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib)
Timepoint [14] 0 0
Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 28 days)
Secondary outcome [15] 0 0
Phase 1 and 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib)
Timepoint [15] 0 0
Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 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
Can healthy volunteers participate?
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
N/A
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/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
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
28/02/2026
Actual
Sample size
Target
875
Accrual to date
Final
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
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Oregon
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Utah
Country [24] 0 0
United States of America
State/province [24] 0 0
Virginia
Country [25] 0 0
United States of America
State/province [25] 0 0
Wisconsin
Country [26] 0 0
Canada
State/province [26] 0 0
British Columbia
Country [27] 0 0
Denmark
State/province [27] 0 0
København Ø
Country [28] 0 0
France
State/province [28] 0 0
Cedex 15
Country [29] 0 0
France
State/province [29] 0 0
Bordeaux
Country [30] 0 0
France
State/province [30] 0 0
Lyon Cedex 08
Country [31] 0 0
France
State/province [31] 0 0
Marseille
Country [32] 0 0
France
State/province [32] 0 0
Montpellier Cedex 5
Country [33] 0 0
France
State/province [33] 0 0
Villejuif Cedex
Country [34] 0 0
Germany
State/province [34] 0 0
Bayern
Country [35] 0 0
Germany
State/province [35] 0 0
Nordrhein-Westfalen
Country [36] 0 0
Hong Kong
State/province [36] 0 0
Shatin, New Territories
Country [37] 0 0
Israel
State/province [37] 0 0
Ramat Gan
Country [38] 0 0
Israel
State/province [38] 0 0
Yerushalayim
Country [39] 0 0
Israel
State/province [39] 0 0
Beer-Sheva
Country [40] 0 0
Israel
State/province [40] 0 0
Jerusalem
Country [41] 0 0
Italy
State/province [41] 0 0
Lombardie
Country [42] 0 0
Japan
State/province [42] 0 0
Aichi
Country [43] 0 0
Japan
State/province [43] 0 0
Chiba
Country [44] 0 0
Japan
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Hokkaido
Country [45] 0 0
Japan
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Hyogo
Country [46] 0 0
Japan
State/province [46] 0 0
Ishikawa
Country [47] 0 0
Japan
State/province [47] 0 0
Osaka
Country [48] 0 0
Japan
State/province [48] 0 0
Shizuoka
Country [49] 0 0
Japan
State/province [49] 0 0
Tokyo
Country [50] 0 0
Japan
State/province [50] 0 0
Tottori
Country [51] 0 0
Japan
State/province [51] 0 0
Fukuoka
Country [52] 0 0
Japan
State/province [52] 0 0
Okayama
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Gyeonggi-do
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Kyonggi-do
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Seoul-teukbyeolsi [Seoul]
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Seoul
Country [57] 0 0
Singapore
State/province [57] 0 0
Singapore
Country [58] 0 0
Spain
State/province [58] 0 0
Barcelona [Barcelona]
Country [59] 0 0
Spain
State/province [59] 0 0
Madrid
Country [60] 0 0
Switzerland
State/province [60] 0 0
Luzern
Country [61] 0 0
Taiwan
State/province [61] 0 0
Taichung
Country [62] 0 0
Taiwan
State/province [62] 0 0
Taipei
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Surrey

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

Ethics approval
Ethics application status

Summary
Brief 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 solid tumors, medullary thyroid cancer
(MTC) and other tumors with RET activation.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03157128
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03157128