Phase 1/2 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03157128 |
Recruitment Status :
Recruiting
First Posted : May 17, 2017
Last Update Posted : July 2, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Non-Small Cell Lung Cancer Medullary Thyroid Cancer Colon Cancer Any Solid Tumor | Drug: LOXO-292 (selpercatinib) | Phase 1 Phase 2 |
Expanded Access : An investigational treatment associated with this study is temporarily not available outside the clinical trial. More info ...
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 970 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2 Study of Oral 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) |
Actual Study Start Date : | May 9, 2017 |
Estimated Primary Completion Date : | March 2022 |
Estimated Study Completion Date : | May 2022 |

Arm | Intervention/treatment |
---|---|
Experimental: LOXO-292 (Selpercatinib)
Phase 1 - Multiple doses of LOXO-292 (selpercatinib) Phase 2 - The maximum tolerated dose (MTD)/recommended dose for Phase 2 (RP2D)
|
Drug: LOXO-292 (selpercatinib)
Oral LOXO-292 (selpercatinib) |
- Phase 1: Maximum tolerated dose (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
- Phase 1: Recommended Phase 2 dose (RP2D) [ Time Frame: The first 28 days of treatment (Cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the patient discontinues from the study) ]
- 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 patients who have not progressed. ]As assessed by RECIST v1.1 or RANO, as appropriate to tumor type, as assessed by independent review committee (IRC)
- Phase 1: Frequency, severity, and relatedness of TEAEs and serious adverse events (SAEs), changes in hematology and blood chemistry values, assessments of physical examinations, vital signs, and electrocardiograms (ECGs). [ Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose) ]
- Phase 1: Plasma concn of LOXO-292 (selpercatinib) and PK parameters, including but not limited to area under the curve from time 0 to 24 hrs (AUC0-24), max drug concn (Cmax), time to max plasma concn (Tmax), and degree of accumulation [ Time Frame: Day 8 of Cycle 1 and Day 8 after Intra-patient Dose Escalation (Phase 1 only) ]
- Phase 1: 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 patients who have not progressed. ]
- 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 patients who have not progressed. ]
- 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 patients who have not progressed. ]
- Phase 2: 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 patients who have not progressed. ]
- Phase 2: 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 patients who have not progressed. ]
- 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 patients who have not progressed. ]
- 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 patients who have not progressed. ]
- 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 patients who have not progressed. ]
- 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 patients who have not progressed. ]
- Phase 2: 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 patients who have not progressed. ]
- Phase 2: Frequency, severity and relatedness of TEAEs and SAEs, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and ECGs. [ Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose) ]
- Phase 2: Plasma concentrations of LOXO-292 (selpercatinib) and PK parameters, including but not limited to AUC0-24, Cmax, and Tmax. [ Time Frame: Day 8 of Cycle 1 and Day 8 after Intra-patient Dose Escalation (Phase 2 only) ]
- Differences in efficacy and safety based on LOXO-292 (selpercatinib) PK parameters. [ Time Frame: Day 8 of Cycle 1 and Day 8 after Intra-patient Dose Escalation ]
- Changes in CEA and calcitonin (patients with MTC) thyroglobulin (non-MTC thyroid cancer patients), ACTH and cortisol (patients with Cushing's disease related to their cancer) with LOXO-292 (selpercatinib) treatment. [ Time Frame: From the time of informed consent, Day 1 and Day 15 of Cycle 1, then with each radiologic disease assessment, and 7 days after the last dose. ]
- Identity of RET gene fusions, mutations, and concurrently activated oncogenic pathways in tumor biopsies and cfDNA. [ Time Frame: Up to 28 days prior to C1D1, Day 1 & Day 15 of Cycle 1, Day 1 of Cycle 3, then approximately every 8 weeks for 1 year, then every 12 weeks, & 7 days after the last dose, for approximately 24 months (or earlier if the patient discontinues from the study) ]
- Changes from baseline in disease-related symptoms and HRQoL, as measured by EORTC QLQ-C30 (adults), PedsQL for teens (ages 13-17 years), and PedsQL for children (age 12 years). [ Time Frame: Day 1 of Cycle 1, then approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose, for approximately 24 months (or earlier if the patient discontinues from the study) ]
- Changes from baseline in disease-related symptoms and HRQoL, as measured by patient bowel diaries (MTC patients only). [ Time Frame: Day 1, Day 8, Day 15, and Day 22 of Cycle 1, and Day 1 of each cycle, and 7 days after the last dose, for approximately 24 months (or earlier if the patient discontinues from the study) ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
For Phase 1
-
Patients with a locally advanced or metastatic solid tumor who:
- have progressed on or are intolerant to standard therapy, or
- 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 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) ≥ 40% (age < 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 (up to 250 patients): Subjects 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 patients with evidence of a RET gene alteration in tumor.
- Cohorts 1 and 2: 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: (up to 200 patients):
- Cohorts 1 and 2 without measurable disease;
- 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 (up to 50 patients):
- Patients who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor due to intolerance may be eligible with prior Sponsor approval.
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:
Patients 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 4 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 patients 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 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. Patients 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) > 470 msec.
- Required treatment with certain strong CYP3A4 inhibitors or inducers and certain prohibited concomitant medications.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03157128
Contact: Patient Advocacy | 855-RET-4-292 (855-738-4292) | clinicaltrials@loxooncology.com | |
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or | 1-317-615-4559 |

Study Director: | Liz Olek, DO, MPH | Loxo Oncology |
Responsible Party: | Loxo Oncology, Inc. |
ClinicalTrials.gov Identifier: | NCT03157128 |
Other Study ID Numbers: |
LOXO-RET-17001 /J2G-OX-JZJA 2017-000800-59 ( EudraCT Number ) |
First Posted: | May 17, 2017 Key Record Dates |
Last Update Posted: | July 2, 2020 |
Last Verified: | June 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 TRIM27-RET TRIM33-RET RET-PTC7 AKAP13-RET FKBP15-RET SPECC1L-RET TBL1XR1-RET BCR-RET FGRF1OP-RET RFG8-RET |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Colonic Neoplasms Thyroid Neoplasms Carcinoma, Neuroendocrine Thyroid Diseases Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Endocrine System Diseases |
Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Endocrine Gland Neoplasms Head and Neck Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Adenocarcinoma |