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

Solid Tumor Clinical Trial

— LIBRETTO-321  

Official title:

A Phase 2 Study of Oral Selpercatinib (LOXO-292) in Patients With Advanced Solid Tumors, Including Rearranged in Transfection (RET) Fusion-Positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04280081
• Other study ID #: 17492
• Secondary ID: J2G-GH-JZJK
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 16, 2020
• Est. completion date: November 20, 2025

Study information

• Verified date: February 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 77
• Est. completion date: November 20, 2025
• Est. primary completion date: March 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Stem Neoplasms
• Carcinoma, Neuroendocrine
• Medullary Thyroid Cancer
• Solid Tumor
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• Selpercatinib
Administered orally

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Southern Medical University Nanfang Hospital	Guangzhou	Guangdong
China	The First Affiated Hospital Of Guangzhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	HangZhou	Zhejiang
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Jinan Central Hospital	Jinan	Shandong
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Shanghai Chest Hospital	Shanghai	Shanghai/China
China	Shanghai East Hospital	Shanghai	Shanghai
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin

Sponsors (2)

Lead Sponsor	Collaborator
Loxo Oncology, Inc.	Eli Lilly and Company

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Analysis Set: Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) as Assessed by Independent Review Committee (IRC)	ORR is the summary measure of best overall response (BOR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR is defined as the best response designation for each participant that is recorded between the date of the first dose of selpercatinib and the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first, and subsequently confirmed. BOR will be categorized as complete response (CR), partial response (PR). CR is defined as Disappearance of all target lesions. Any pathologic nodes (whether target or non-target lesions) must have a reduction in short axis diameter (SAD) to less than 10 mm. PR At least 30% decrease in the sum of the diameters (SOD) (LD for non-nodal lesions and SAD for nodal lesions) of target lesions, taking as reference the baseline sum LD.	Date of First Dose to Disease Progression or Death (up to 12 Months)
Primary	Enrolled Population: Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) as Assessed by IRC	ORR is the summary measure of best overall response (BOR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR is defined as the best response designation for each participant that is recorded between the date of the first dose of selpercatinib and the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first, and subsequently confirmed. BOR will be categorized as complete response (CR), partial response (PR). CR is defined as Disappearance of all target lesions. Any pathologic nodes (whether target or non-target lesions) must have a reduction in short axis diameter (SAD) to less than 10 mm. PR At least 30% decrease in the sum of the diameters (SOD) (LD for non-nodal lesions and SAD for nodal lesions) of target lesions, taking as reference the baseline sum LD.	Date of First Dose to Disease Progression or Death (Up to 12 months)
Secondary	Enrolled Population: Duration of Response (DoR) as Assessed by IRC	DOR is defined as the number of months from the start date of PR or CR (whichever response is recorded first), and subsequently confirmed, to the date of disease progression or death, whichever occurs earlier.	Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)
Secondary	Enrolled Population: Time to Response (TTR) as Assessed by IRC	TTR is defined as the number of months elapsed between the date of the first dose of selpercatinib and the first documentation of objective response (CR or PR, whichever occurs earlier) that is subsequently confirmed.	Date of First Dose to First Occurrence of Confirmed Tumor Response (Up to 6 months)
Secondary	Enrolled Population: Time to Best Response (TTBR) as Assessed by IRC	TTR is defined as the number of months elapsed between the date of the first dose of selpercatinib and the first documentation of objective response (CR or PR, whichever occurs earlier) that is subsequently confirmed.	Date of First Dose to First Occurrence of PR (If Subject's Best Overall Response [BOR] is PR) or CR (If Subject's BOR is CR) (Up to 8 months)
Secondary	Enrolled Population: Clinical Benefit Rate (CBR): Percentage of Participants Who Achieve CR, PR, or Stable Disease (SD) With a Duration of At Least 16 or More Weeks as Assessed by IRC	CBR based on the percentage of participants with best overall response of CR, PR, or stable disease (SD) lasting 16 or more weeks following initiation of selpercatinib as assessed by IRC. CR is defined as disappearance of all target lesions. Any pathologic nodes (whether target or non-target lesions) must have a reduction in short axis diameter (SAD) to less than 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters (SOD) (LD for non-nodal lesions) and SAD for nodal lesions) of target lesions, taking as reference the baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.	Baseline through Disease Progression or Death Due to Any Cause (Up to 12 Months)
Secondary	Enrolled Population: Progression Free Survival (PFS) as Assessed by IRC	PFS is defined as the number of months elapsed between the date of the first dose and the earliest date of documented disease progression or death (whatever the cause). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest sum on study) for target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5.0 mm. Progressive disease for non-target lesion is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.	Baseline to Progressive Disease or Death from Any Cause (Up to 12 Months)
Secondary	Enrolled Population: Overall Survival (OS)	OS is defined as the number of months elapsed between the date of the first dose and the date of death (whatever the cause). Participants who are alive or lost to follow-up as of the data cutoff date will be right-censored.	Baseline to Date of Death from Any Cause (Up to 12 Months)
Secondary	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Selpercatinib	Serial blood samples for intensive PK monitoring will be collected for 12 participants.	PK: Cycle 1 Day 1: Predose, 1 h, 2, h, 4 h, 8 h, 12 h postdose PK: Cycle 1 Day 8: Predose, 1 h, 2, h, 4 h, 8 h postdose