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)

• ClinicalTrials.gov Identifier: NCT04280081
• Recruitment Status: Active, not recruiting
• First Posted: February 21, 2020
• Results First Posted: June 2, 2022
• Last Update Posted: June 2, 2022
• Sponsor: Loxo Oncology, Inc.
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company ( Loxo Oncology, Inc. )

Tracking Information

• First Submitted Date: February 20, 2020
• First Posted Date: February 21, 2020
• Results First Submitted Date: March 22, 2022
• Results First Posted Date: June 2, 2022
• Last Update Posted Date: June 2, 2022
• Actual Study Start Date: March 16, 2020
• Actual Primary Completion Date: March 25, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2022)

• 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) [ Time Frame: Date of First Dose to Disease Progression or Death (up to 12 Months) ]
  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.
• Enrolled Population: Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) as Assessed by IRC [ Time Frame: Date of First Dose to Disease Progression or Death (Up to 12 months) ]
  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.

Original Primary Outcome Measures (submitted: February 20, 2020)

Overall Response Rate (ORR): Percentage of Participants with Complete Response (CR) or Partial Response (PR) by Independent Review Committee [ Time Frame: Baseline through Disease Progression or Death (Estimated at up to 30 Months) ]

ORR: Percentage of Participants with CR or PR by IRC

Current Secondary Outcome Measures (submitted: May 9, 2022)

• Enrolled Population: Duration of Response (DoR) as Assessed by IRC [ Time Frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months) ]
  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.
• Enrolled Population: Time to Response (TTR) as Assessed by IRC [ Time Frame: Date of First Dose to First Occurrence of Confirmed Tumor Response (Up to 6 months) ]
  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.
• Enrolled Population: Time to Best Response (TTBR) as Assessed by IRC [ Time Frame: 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) ]
  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.
• 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 [ Time Frame: Baseline through Disease Progression or Death Due to Any Cause (Up to 12 Months) ]
  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.
• Enrolled Population: Progression Free Survival (PFS) as Assessed by IRC [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Up to 12 Months) ]
  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.
• Enrolled Population: Overall Survival (OS) [ Time Frame: Baseline to Date of Death from Any Cause (Up to 12 Months) ]
  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.
• Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Selpercatinib [ Time Frame: 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 ]
  Serial blood samples for intensive PK monitoring will be collected for 12 participants.

Original Secondary Outcome Measures (submitted: February 20, 2020)

• Duration of Response (DoR) by IRC [ Time Frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated at up to 30 Months) ]
  DoR by IRC
• Time to Response (TTR) by IRC [ Time Frame: Baseline to Date of CR or PR (Estimated at up to 30 Months) ]
  TTR by IRC
• 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 [ Time Frame: Baseline through Disease Progression or Death Due to Any Cause (Estimated at up to 30 Months) ]
  CBR: Percentage of Participants Who Achieve CR, PR or SD With a Duration of At Least 16 or More Weeks
• Progression Free Survival (PFS) by IRC [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 30 Months) ]
  PFS by IRC
• Overall Survival (OS) [ Time Frame: Baseline to Date of Death from Any Cause (Estimated at up to 60 Months) ]
  OS
• Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Selpercatinib [ Time Frame: Baseline through End of Study (Estimated at up to 60 Months) ]
  PK: AUC of Selpercatinib

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Solid Tumor
• Medullary Thyroid Cancer

Intervention

Drug: Selpercatinib

Administered orally

Other Names:

• LY3527723
• LOXO-292

Study Arms

Experimental: Selpercatinib

Selpercatinib 160 milligrams (mg) administered orally twice daily (BID).

Intervention: Drug: Selpercatinib

Publications *

• Zheng X, Ji Q, Sun Y, Ge M, Zhang B, Cheng Y, Lei S, Shi F, Guo Y, Li L, Chen L, Shao J, Zhang W, Gao M. Efficacy and safety of selpercatinib in Chinese patients with advanced RET-altered thyroid cancers: results from the phase II LIBRETTO-321 study. Ther Adv Med Oncol. 2022 Aug 29;14:17588359221119318. doi: 10.1177/17588359221119318. eCollection 2022.
• Lu S, Cheng Y, Huang D, Sun Y, Wu L, Zhou C, Guo Y, Shao J, Zhang W, Zhou J. Efficacy and safety of selpercatinib in Chinese patients with advanced RET fusion-positive non-small-cell lung cancer: a phase II clinical trial (LIBRETTO-321). Ther Adv Med Oncol. 2022 Jul 28;14:17588359221105020. doi: 10.1177/17588359221105020. eCollection 2022.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 22, 2022): 77
• Original Estimated Enrollment (submitted: February 20, 2020): 75
• Estimated Study Completion Date: November 20, 2025
• Actual Primary Completion Date: March 25, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04280081
• Other Study ID Numbers: 17492; J2G-GH-JZJK ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: http://vivli.org/

• Current Responsible Party: Eli Lilly and Company ( Loxo Oncology, Inc. )
• Original Responsible Party: Eli Lilly and Company
• Current Study Sponsor: Loxo Oncology, Inc.
• Original Study Sponsor: Eli Lilly and Company
• Collaborators: Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM; Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: May 2022