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

NCT04280081 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 17492J2G-GH-JZJK
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 13

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.

Conditions

Solid Tumor; Medullary Thyroid Cancer

Keywords

Non-Small Cell Lung Cancer; NSCLC; Targeted Therapy; Medullary Thyroid Carcinoma; Thyroid Cancer; RET Alteration; MTC

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (7)

• Enrolled Population: Duration of Response (DoR) as Assessed by IRC

  Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)

• Enrolled Population: Time to Response (TTR) as Assessed by IRC

  Date of First Dose to First Occurrence of Confirmed Tumor Response (Up to 6 months)

• Enrolled Population: Time to Best Response (TTBR) as Assessed by IRC

  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)

• 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

  Baseline through Disease Progression or Death Due to Any Cause (Up to 12 Months)

• Enrolled Population: Progression Free Survival (PFS) as Assessed by IRC

  Baseline to Progressive Disease or Death from Any Cause (Up to 12 Months)

Study Arms (1)

Selpercatinib

EXPERIMENTAL

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

Drug: Selpercatinib

Interventions

Selpercatinib DRUG

Administered orally

Also known as: LY3527723, LOXO-292

Selpercatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (13)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

The First Affiated Hospital Of Guangzhou Medical University

Guangzhou, Guangdong, 510120, China

Location

Southern Medical University Nanfang Hospital

Guangzhou, Guangdong, 510515, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130000, China

Location

Jinan Central Hospital

Jinan, Shandong, 250013, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

Location

Shanghai Chest Hospital

Shanghai, Shanghai/China, 200030, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, 310014, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Related Publications (5)

• Lu S, Cheng Y, Huang D, Sun Y, Wu L, Zhou C, Zhou J, Guo Y, Shao J, Zhang W. Selpercatinib in Chinese patients with RET-fusion-positive non-small-cell lung cancer: updated efficacy and safety analysis from the LIBRETTO-321 phase II trial. Ther Adv Med Oncol. 2025 Jan 1;17:17588359241307199. doi: 10.1177/17588359241307199. eCollection 2025.

  PMID: 39759832 DERIVED

• Lu S, Zheng X, Sun Y, Huang D, Wu L, Ji Q, Zhou C, Zhou J, Guo Y, Ge M, Ding D, Shao J, Zhang W, Gao M, Cheng Y. Patient-reported outcomes following selpercatinib treatment in Chinese patients with advanced RET fusion-positive non-small-cell lung cancer and thyroid cancer, and RET-mutant medullary thyroid cancer in the phase II LIBRETTO-321 trial. Ther Adv Med Oncol. 2023 Aug 25;15:17588359231189429. doi: 10.1177/17588359231189429. eCollection 2023.

  PMID: 37655205 DERIVED

• Cheng Y, Huang D, Zhou J, Zhou C, Sun Y, Wu L, Guo Y, Jingxin S, Zhang W, Lu S. Intracranial Activity of Selpercatinib in Chinese Patients With Advanced RET Fusion-Positive Non-Small-Cell Lung Cancer in the Phase II LIBRETTO-321 Trial. JCO Precis Oncol. 2023 Jun;7:e2200708. doi: 10.1200/PO.22.00708.

  PMID: 37315261 DERIVED

• 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.

  PMID: 36062046 DERIVED

• 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.

  PMID: 35923928 DERIVED

MeSH Terms

Conditions

Carcinoma, Medullary; Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms

Interventions

selpercatinib

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-595-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2020
• First Posted: February 21, 2020
• Study Start: March 16, 2020
• Primary Completion: March 25, 2021
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 24, 2026
• Results First Posted: June 2, 2022

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

CN (13)