Clinical trial NCT04280081: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Solid Tumor
Medullary Thyroid Cancer
Keywords: Non-Small Cell Lung Cancer
NSCLC
Targeted Therapy
Medullary Thyroid Carcinoma
Thyroid Cancer
RET Alteration
MTC
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2020-02-21
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
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)
timeFrame: Date of First Dose to Disease Progression or Death (up to 12 Months)
measure: Enrolled Population: Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) as Assessed by IRC
timeFrame: Date of First Dose to Disease Progression or Death (Up to 12 months)
Secondary outcomes:
measure: Enrolled Population: Duration of Response (DoR) as Assessed by IRC
timeFrame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)
measure: Enrolled Population: Time to Response (TTR) as Assessed by IRC
timeFrame: Date of First Dose to First Occurrence of Confirmed Tumor Response (Up to 6 months)
measure: Enrolled Population: Time to Best Response (TTBR) as Assessed by IRC
timeFrame: 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)
measure: 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
timeFrame: Baseline through Disease Progression or Death Due to Any Cause (Up to 12 Months)
measure: Enrolled Population: Progression Free Survival (PFS) as Assessed by IRC
timeFrame: Baseline to Progressive Disease or Death from Any Cause (Up to 12 Months)
measure: Enrolled Population: Overall Survival (OS)
timeFrame: Baseline to Date of Death from Any Cause (Up to 12 Months)
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Selpercatinib
timeFrame: 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
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: The First Affiated Hospital Of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital
state: Guangdong
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai/China
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: HangZhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.