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 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

Sponsors

Lead Sponsor: Eli Lilly and Company

Collaborator: Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company

Source Eli Lilly and Company
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.

Overall Status Recruiting
Start Date March 16, 2020
Completion Date April 30, 2023
Primary Completion Date May 31, 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Overall Response Rate (ORR): Percentage of Participants with Complete Response (CR) or Partial Response (PR) by Independent Review Committee Baseline through Disease Progression or Death (Estimated at up to 30 Months)
Secondary Outcome
Measure Time Frame
Duration of Response (DoR) by IRC Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated at up to 30 Months)
Time to Response (TTR) by IRC Baseline to Date of CR or PR (Estimated at up to 30 Months)
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 Baseline through Disease Progression or Death Due to Any Cause (Estimated at up to 30 Months)
Progression Free Survival (PFS) by IRC Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 30 Months)
Overall Survival (OS) Baseline to Date of Death from Any Cause (Estimated at up to 60 Months)
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Selpercatinib Baseline through End of Study (Estimated at up to 60 Months)
Enrollment 75
Condition
Intervention

Intervention Type: Drug

Intervention Name: Selpercatinib

Description: Administered orally

Arm Group Label: Selpercatinib

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Study Director Eli Lilly and Company
Overall Contact

Last Name: There will be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Phone: 1-317-615-4559

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
Nanfang Affiliated Hospital South Medical University | Guangzhou, Guangdong, 510515, China Not yet recruiting 008613632101395 Lei Shangtong Principal Investigator
The First Affiated Hospital Of Guangzhou Medical Collage | Guangzhou, Guangzhou, 510120, China Recruiting 008613560351186 Zhou Chengzhi Principal Investigator
Hunan Cancer Hospital | Changsha, Hunan, 410013, China Recruiting 8613170419973 Lin Wu Principal Investigator
Hunan Cancer Hospital | Changsha, Hunan, 410013, China Recruiting 8613974875587 Feng Shi Principal Investigator
Jilin Province Tumor Hospital | Changchun, Jilin, 130012, China Recruiting 8613943012851 Ying Cheng Principal Investigator
The First Hospital of Jilin University | Changchun, Jilin, 130021, China Not yet recruiting 8613756661294 Guang Chen Principal Investigator
Jinan Central Hospital | Jinan, Shandong, 250013, China Recruiting 13370582181 Yuping Sun Principal Investigator
Shanghai Chest Hospital | Shanghai, Shanghai/China, 200030, China Recruiting 8613601813062 Shun Lu Principal Investigator
First Affiliated Hospital of Kunming Medical University | Kunming, Yunnan, 650032, China Not yet recruiting 8613708467986 Ruochuan Cheng Principal Investigator
Zhejiang Cancer Hospital | Hang Zhou, Zhejiang, 310022, China Not yet recruiting 861366670158 Linfa Li Principal Investigator
First Affiliated Hosp of College of Med, Zhejiang University | Hangzhou, Zhejiang, 310003, China Recruiting 13505719970 Jianying Ying Zhou Principal Investigator
Zhejiang Provincial People's Hospital | Hangzhou, Zhejiang, 310014, China Not yet recruiting 13605813782 Minghua Ge Principal Investigator
Beijing Cancer Hospital | Beijing, 100142, China Recruiting 6168121122178 Zhang Bin Principal Investigator
Beijing Peking Union Medical College Hospital | Beijing, 100730, China Not yet recruiting 13671116837 Lin Yansong Principal Investigator
Fudan University Shanghai Cancer Center | Shanghai, 200032, China Recruiting 13601698395 Qinghai Ji Principal Investigator
Shanghai East Hospital | Shanghai, 200433, China Recruiting 8613501678472 Guo Ye Principal Investigator
Tianjin Medical University Cancer Institute & Hospital | Tianjin, 300060, China Recruiting 8622221232 dingzhi huang Principal Investigator
Tianjin Medical University Cancer Institute & Hospital | Tianjin, 300060, China Recruiting 008613802088311 Ming Gao Principal Investigator
Tongji Medical College of Huazhong University of Science and Technology | Wuhan, 430030, China Not yet recruiting 02785726114 xiaorong dong Principal Investigator
Location Countries

China

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Selpercatinib

Type: Experimental

Description: Selpercatinib given orally.

Acronym LIBRETTO-321
Patient Data Yes
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov