A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation (LIBRETTO-321)

Lilly

Status and phase

Active, not recruiting

Phase 2

Conditions

Solid Tumor

Medullary Thyroid Cancer

Treatments

Drug: Selpercatinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT04280081

J2G-GH-JZJK (Other Identifier)

17492

Details and patient eligibility

About

The reason for this study is to see if the study drug selpercatinib is safe and effective in participants in China with rearranged during transfection (RET) fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation.

Enrollment

77 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Participants with a locally advanced or metastatic solid tumor.
Evidence of a RET gene alteration in tumor and/or blood.
Measurable or non-measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2, with no sudden deterioration 2 weeks prior to the first dose of study treatment.
Archived tumor tissue sample available for cohort 1 and 2.
Cohorts 1 and 2: failed or intolerant to standard of care.
Cohorts 1-2: enrollment will be restricted to participants with evidence of a RET gene alteration in tumor (i.e., not just blood). However, a positive germline DNA test for a RET gene mutation as defined in the protocol is acceptable in the absence of tumor tissue testing for participants with MTC.
Cohorts 1-2: at least one measurable lesion as defined by RECIST v1.1 and not previously irradiated (unless progressive disease for the irradiated lesion[s] has been radiographically documented).

Exclusion criteria

Cohorts 1-2, an additional validated oncogenic driver that could cause resistance to selpercatinib treatment if known.
Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor(s), such as BLU-667, RXDX-105, etc).
Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
Any unresolved toxicities from prior therapy greater than common terminology criteria for adverse events (CTCAE) Grade 1 except where otherwise noted in this eligibility criteria at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum therapy-related neuropathy.
Symptomatic primary central nervous system (CNS) tumor, symptomatic CNS metastasis, leptomeningeal carcinomatosis, or untreated spinal cord compression.
Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of selpercatinib or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470 milliseconds.
History of Human Immunodeficiency Virus (known HIV 1/2 antibodies positive); participants with unknown HIV status do not need to be tested.
History of active hepatitis B (known positive hepatitis B surface antigen [HbsAg] and quantitative hepatitis B DNA greater than the upper limit of detection of the assay) or C (known positive hepatitis C antibody and quantitative hepatitis C RNA greater than the upper limit of detection of the assay); participants with unknown hepatitis B/hepatitis C status do not need to be tested.
Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment. Screening for chronic conditions is not required.
Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
Uncontrolled symptomatic hyperthyroidism or hypothyroidism
Uncontrolled symptomatic hypercalcemia or hypocalcemia.
Concurrent use of drugs known to prolong QTc.
Pregnancy or lactation. Breast-feeding should be interrupted when selpercatinib is started; breast-feeding can be resumed 3 months after discontinuation of selpercatinib.
Active second malignancy other than minor treatment of indolent cancers with prior sponsor approval.