AzTrials
AzTrials

Solid TumorPhase 2LIBRETTO-321NCT04280081

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

A Phase 2 study testing Selpercatinib in people with Solid Tumor and Medullary Thyroid Cancer, run by Eli Lilly and Company at 13 sites in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor, Medullary Thyroid Cancer
What is being tested?
Selpercatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
13 sitesChina
Study dates
16 Mar 2020to Nov 2028
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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.
Show all 15Show fewer
  • 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.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

China13 sites

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100142

  • Jilin Cancer Hospital

    Changchun, Jilin, 130000

  • Hunan Cancer Hospital

    Changsha, Hunan, 410013

  • The First Affiated Hospital Of Guangzhou Medical University

    Guangzhou, Guangdong, 510120

  • Southern Medical University Nanfang Hospital

    Guangzhou, Guangdong, 510515

  • The First Affiliated Hospital, Zhejiang University

    Hangzhou, Zhejiang, 310003

  • Zhejiang Provincial People's Hospital

    Hangzhou, Zhejiang, 310014

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, 310022

  • Jinan Central Hospital

    Jinan, Shandong, 250013

  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality, 200032

  • Shanghai East Hospital

    Shanghai, Shanghai Municipality, 200120

  • Shanghai Chest Hospital

    Shanghai, Shanghai/China, 200030

  • Tianjin Medical University Cancer Institute & Hospital

    Tianjin, Tianjin Municipality, 300060

Other trials in China

About this study

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

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.

Being tested
Selpercatinib
Keywords
Non-Small Cell Lung Cancer, NSCLC, Targeted Therapy, Medullary Thyroid Carcinoma, Thyroid Cancer, RET Alteration, MTC
Medical subject headings
Carcinoma, Medullary, Carcinoma, Non-Small-Cell Lung, Thyroid Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SelpercatinibDrug

    Also called LY3527723, LOXO-292

    Administered orally

Study groups in NCT04280081
Study groupRoleWhat they receive
SelpercatinibExperimentalSelpercatinib 160 milligrams (mg) administered orally twice daily (BID).
Receives: Drug: Selpercatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Date of First Dose to Disease Progression or Death (up to 12 Months)

  2. 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.

    Measured: Date of First Dose to Disease Progression or Death (Up to 12 months)

Secondary outcomes (7)

  1. 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.

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

  2. 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.

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

  3. 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.

    Measured: 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)

  4. 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.

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

  5. 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.

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

  6. 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.

    Measured: Baseline to Date of Death from Any Cause (Up to 12 Months)

  7. 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.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2020
  2. Study start16 Mar 2020
  3. Primary completion25 Mar 2021
  4. Study completionNov 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04280081
Sponsor's protocol ID
17492
Other IDs
J2G-GH-JZJK
Acronym
LIBRETTO-321
Status last verified
Jul 2026
First submitted
20 Feb 2020
Last updated
7 Aug 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 39759832

  • 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.

    PubMed 37655205

  • 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.

    PubMed 37315261

  • 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.

    PubMed 36062046

  • 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.

    PubMed 35923928

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Selpercatinib in people with Solid Tumor and Medullary Thyroid Cancer, run by Eli Lilly and Company at 13 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04280081, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in