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JOURNAL ONKOLOGIE – STUDIE
LIBRETTO-001

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

Rekrutierend

NCT-Nummer:
NCT03157128

Studienbeginn:
Mai 2017

Letztes Update:
04.03.2024

Wirkstoff:
LOXO-292

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Colonic Neoplasms, Thyroid Neoplasms, Carcinoma, Neuroendocrine, Thyroid Diseases

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
-

Sponsor:
Loxo Oncology, Inc.

Collaborator:
Eli Lilly and Company

Studienleiter

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

Kontakt

There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
Kontakt:
Phone: 1-317-615-4559
E-Mail: ClinicalTrials.gov@lilly.com» Kontaktdaten anzeigen

Studienlocations
(3 von 84)

University of Chicago Medicine-Comprehensive Cancer Center
60637 Chicago
United StatesRekrutierend» Google-Maps
Thomas Jefferson University
19107 Philadelphia
United StatesRekrutierend» Google-Maps
Shaare Zedek Medical Center
9103102 Jerusalem
IsraelNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This is an open-label, multi-center Phase 1/2 study in participants with advanced solid

tumors, including RET fusion-positive solid tumors, MTC, and other tumors with RET

activation. The trial will be conducted in 2 parts: Phase 1 (dose escalation - completed) and

phase 2 (dose expansion). Participants with advanced cancer are eligible if they have

progressed on or are intolerant to available standard therapies, or no standard or available

curative therapy exists, or in the opinion of the Investigator, they would be unlikely to

tolerate or derive significant clinical benefit from appropriate standard of care therapy, or

they declined standard therapy. A dose of 160 milligrams (mg) twice a day (BID) has been

selected as the recommended phase 2 dose (RP2D). Approximately 875 participants with advanced

solid tumors harboring a RET gene alteration in tumor and/or blood will be enrolled to one of

seven phase 2 cohorts:

- Cohort 1: Advanced RET fusion positive solid tumor other than NSCLC or thyroid cancer

for participants who progressed on or intolerant to first line therapy (open)

- Cohort 2: Advanced RET fusion positive solid tumor other than NSCLC or thyroid cancer

for treatment naïve participants (open)

- Cohort 3: Advanced RET-mutant MTC participants who progressed on or intolerant to first

line therapy (closed)

- Cohort 4: Advanced RET-mutant MTC participants who are treatment naïve (closed)

- Cohort 5: Advanced RET-altered solid tumor for participants other than NSCLC or thyroid

cancer and RET-mutant MEN2 spectrum tumors (e.g. pheochromocytoma) otherwise ineligible

for cohorts 1-4. See details in inclusion/exclusion criteria (open)

- Cohort 6: Participants otherwise eligible for Cohorts 1-5 who discontinued another RET

inhibitor due to intolerance may be eligible with prior Sponsor approval (closed)

- Cohort 7: RET fusion positive early-stage non-small cell lung cancer (NSCLC)

participants who are candidates for definitive surgery. Participants will receive

selpercatinib in a neoadjuvant and adjuvant setting. Participants will be followed for

disease recurrence for up to 5 years from the date of surgery (closed)

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. Phase 1: MTD (Time Frame - The first 28 days of treatment (Cycle 1)):
Incidence rate and category of dose limiting toxicities (DLTs) during the first 28-day cycle of LOXO-292 (selpercatinib) treatment

2. Phase 1: RP2D (Time Frame - The first 28 days of treatment (Cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the participant discontinues from the study)):
Phase 1: RP2D

3. Phase 2: Objective Response Rate (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.):
As assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Response Assessment in Neuro-Oncology (RANO), as appropriate to tumor type, as assessed by independent review committee (IRC)

Secondary outcome:

1. Phase 1: Number of Participants with a Treatment-Related Adverse Event(s) (TRAE[s]) (Time Frame - From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)):
Phase 1: Number of Participants with a TRAE(s)

2. Phase 1: Number of Participants with an Abnormal Laboratory or Physical Exam Result(s) (Time Frame - From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)):
Phase 1: Number of Participants with an Abnormal Laboratory or Physical Exam Result(s)

3. Phase 1: Overall Response Rate (ORR) based on RECIST 1.1 or RANO, as Appropriate to Tumor Type (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed):
Phase 1: ORR based on RECIST 1.1 or RANO, as Appropriate to Tumor Type

4. Phase 2: ORR (by Investigator) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed):
Phase 2: ORR (by Investigator)

5. Phase 2: Best Change in Tumor Size from Baseline (by IRC and Investigator) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed):
Phase 2: Best Change in Tumor Size from Baseline (by IRC and Investigator)

6. Phase 2: Duration of Response (DOR; by IRC and Investigator) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed):
Phase 2: DOR (by IRC and Investigator)

7. Phase 2: Central Nervous System (CNS) ORR (by IRC) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed):
Phase 2: CNS ORR (by IRC)

8. Phase 2: CNS DOR (by IRC) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed):
Phase 2: CNS DOR (by IRC)

9. Phase 2: Time to Any and Best Response (by IRC and Investigator) (Time Frame - every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed):
Phase 2: Time to Any and Best Response (by IRC and Investigator)

10. Phase 2: CBR (by IRC and Investigator) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed):
Phase 2: CBR (by IRC and Investigator)

11. Phase 2: PFS (by IRC and Investigator) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed):
Phase 2: PFS (by IRC and Investigator)

12. Phase 2: Overall Survival (OS) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed):
Phase 2: OS

13. Phase 2: Percentage of Participants with any Serious Adverse Event (SAE[s]) (Time Frame - From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)):
Phase 2: Percentage of Participants with any SAE(s)

14. Phase 1 and 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib) (Time Frame - Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 28 days)):
Phase 1 and 2: PK: AUC of LOXO-292 (Selpercatinib)

15. Phase 1 and 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib) (Time Frame - Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 28 days)):
Phase 1 and 2: PK: Cmax of LOXO-292 (Selpercatinib)

Geprüfte Regime

  • LOXO-292 (Selpercatinib / LY3527723 / ):
    Oral LOXO-292

Quelle: ClinicalTrials.gov


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