LIBRETTO-321: 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

• Sponsor: Loxo Oncology, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04280081
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 77
• Locations: 13
• Arm: 1
• Anticipated Duration (Months): 68.2
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor; Medullary Thyroid Cancer	Drug: Selpercatinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 16, 2020
• Actual Primary Completion Date: Mar 25, 2021
• Anticipated Study Completion Date: Nov 20, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Selpercatinib Selpercatinib 160 milligrams (mg) administered orally twice daily (BID).	Drug: Selpercatinib; Administered orally; Other Names: LY3527723 LOXO-292

Outcome Measures

Primary Outcome Measures

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) [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.

2. Enrolled Population: Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) as Assessed by IRC [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.

Secondary Outcome Measures

1. 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)]

   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.

2. 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)]

   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.

3. 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)]

   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.

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 [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.

5. Enrolled Population: Progression Free Survival (PFS) as Assessed by IRC [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.

6. Enrolled Population: Overall Survival (OS) [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.

7. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Selpercatinib [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nanfang Affiliated Hospital South Medical University	Guangzhou	Guangdong	China	510515
2	The First Affiated Hospital Of Guangzhou Medical Collage	Guangzhou	Guangzhou	China	510120
3	Hunan Cancer Hospital	Changsha	Hunan	China	410013
4	Jilin Province Tumor Hospital	Changchun	Jilin	China	130012
5	Jinan Central Hospital	Jinan	Shandong	China	250013
6	Shanghai Chest Hospital	Shanghai	Shanghai/China	China	200030
7	Zhejiang Cancer Hospital	Hang Zhou	Zhejiang	China	310022
8	First Affiliated Hosp of College of Med, Zhejiang University	Hangzhou	Zhejiang	China	310003
9	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang	China	310014
10	Beijing Cancer Hospital	Beijing		China	100142
11	Fudan University Shanghai Cancer Center	Shanghai		China	200032
12	Shanghai East Hospital	Shanghai		China	200433
13	Tianjin Medical University Cancer Institute & Hospital	Tianjin		China	300060

Sponsors and Collaborators

• Loxo Oncology, Inc.
• 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

Study Documents (Full-Text)

• Study Protocol - Feb 1, 2021
• Statistical Analysis Plan - Apr 25, 2021

More Information

Publications

None provided.

• Responsible Party: Loxo Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT04280081
• Other Study ID Numbers: 17492; J2G-GH-JZJK
• First Posted: Feb 21, 2020
• Last Update Posted: Jun 2, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by Loxo Oncology, Inc.: Non-Small Cell Lung Cancer; NSCLC; Targeted Therapy; Medullary Thyroid Carcinoma; Thyroid Cancer; RET Alteration; MTC
• Additional relevant MeSH terms: Thyroid Neoplasms; Carcinoma, Neuroendocrine; Brain Stem Neoplasms; Thyroid Diseases

Study Results

Participant Flow

Recruitment Details	Enrollment for this study was based on tumor type.
Pre-assignment Detail	Primary analysis set (PAS) is defined as rearranged transfection (RET) fusion positive non-small cell lung cancer (NSCLC) and thyroid cancer (TC) and RET mutant medullary thyroid cancer (MTC). Enrolled population is defined as all eligible participants.

Arm/Group Title	Selpercatinib
Arm/Group Description	160 milligram (mg) Selpercatinib administered orally twice daily (BID).
Period Title: Overall Study
STARTED	77
Enrolled: All NSCLC	47
Enrolled: All TC	1
Enrolled: All MTC	29
PAS: RET Fusion Positive NSCLC	26
PAS: RET Fusion Positive TC	1
PAS: Advance RET-mutant MTC	26
COMPLETED	65
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Selpercatinib
Arm/Group Description	160 mg Selpercatinib administered orally BID.
Overall Participants	77
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.60 (12.87)
Sex: Female, Male (Count of Participants)
Female	33 42.9%
Male	44 57.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	77 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
China	77 100%

Outcome Measures

1. Primary Outcome

Title	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)
Description	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.
Time Frame	Date of First Dose to Disease Progression or Death (up to 12 Months)

Outcome Measure Data

Analysis Population Description

All treated participants who have confirmed RET fusion positive solid tumor NSCLC,TC, or RET mutant MTC by central lab, respectively.

Arm/Group Title	RET Fusion Positive Non-small Cell Lung Cancer (NSCLC) Cohort 1	RET Fusion Positive Thyroid Cancer (TC) Cohort 1	RET Mutant Medullary Thyroid Cancer (MTC) Cohort 2
Arm/Group Description	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.
Measure Participants	26	1	26
Complete Response	3.8 4.9%	0 NaN	7.7 NaN
Partial Response	65.4 84.9%	100.0 NaN	50.0 NaN
Overall Response (CR/PR)	69.2 89.9%	100.0 NaN	57.7 NaN

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All eligible participants.

Arm/Group Title	Non-small Cell Lung Cancer (All NSCLC)	Thyroid Cancer (All TC)	Medullary Thyroid Cancer (All MTC)
Arm/Group Description	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.
Measure Participants	47	1	29
Complete Response	6.4 8.3%	0 NaN	10.3 NaN
Partial Response	59.6 77.4%	100.0 NaN	48.3 NaN
Overall Response (CR/PR)	66.0 85.7%	100.0 NaN	58.6 NaN

3. Secondary Outcome

Title	Enrolled Population: Duration of Response (DoR) as Assessed by IRC
Description	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.
Time Frame	Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)

Outcome Measure Data

Analysis Population Description

All eligible participants with confirmed response. Number of participants censored: All NSCLC = 30, All TC = 1, and All MTC = 16.

Arm/Group Title	All NSCLC	All TC	All MTC
Arm/Group Description	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.
Measure Participants	31	1	17
Median (95% Confidence Interval) [months]	NA	NA	NA

4. Secondary Outcome

Title	Enrolled Population: Time to Response (TTR) as Assessed by IRC
Description	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.
Time Frame	Date of First Dose to First Occurrence of Confirmed Tumor Response (Up to 6 months)

Outcome Measure Data

Analysis Population Description

All eligible participants with confirmed response.

Arm/Group Title	All NSCLC	All TC	All MTC
Arm/Group Description	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.
Measure Participants	31	1	17
Median (Inter-Quartile Range) [months]	1.84	1.74	1.84

5. Secondary Outcome

Title	Enrolled Population: Time to Best Response (TTBR) as Assessed by IRC
Description	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.
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)

Outcome Measure Data

Analysis Population Description

All eligible patients with confirmed response.

Arm/Group Title	All NSCLC	All TC	All MTC
Arm/Group Description	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.
Measure Participants	31	1	17
Geometric Mean (Inter-Quartile Range) [months]	1.84	1.74	1.87

6. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline through Disease Progression or Death Due to Any Cause (Up to 12 Months)

Outcome Measure Data

Analysis Population Description

All eligible participants.

Arm/Group Title	All NSCLC	All TC	All MTC
Arm/Group Description	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.
Measure Participants	47	1	29
Number (95% Confidence Interval) [percentage of participants]	76.6 99.5%	100.0 NaN	65.5 NaN

7. Secondary Outcome

Title	Enrolled Population: Progression Free Survival (PFS) as Assessed by IRC
Description	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.
Time Frame	Baseline to Progressive Disease or Death from Any Cause (Up to 12 Months)

Outcome Measure Data

Analysis Population Description

All eligible participants. Number of participants censored: All NSCLC = 40; All TC = 1, and All MTC = 28

Arm/Group Title	All NSCLC	All TC	All MTC
Arm/Group Description	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.
Measure Participants	47	1	29
Median (95% Confidence Interval) [months]	NA	NA	NA

8. Secondary Outcome

Title	Enrolled Population: Overall Survival (OS)
Description	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.
Time Frame	Baseline to Date of Death from Any Cause (Up to 12 Months)

Outcome Measure Data

Analysis Population Description

All eligible participants. Number of participants censored: All NSCLC = 42, All TC = 1, and All MTC = 28.

Arm/Group Title	All NSCLC	All TC	All MTC
Arm/Group Description	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.	160 mg Selpercatinib administered orally BID.
Measure Participants	47	1	29
Median (95% Confidence Interval) [months]	NA	NA	NA

9. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Selpercatinib
Description	Serial blood samples for intensive PK monitoring will be collected for 12 participants.
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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had evaluable intensive PK data per protocol.

Arm/Group Title	Selpercatinib
Arm/Group Description	160 mg Selpercatinib administered orally BID.
Measure Participants	12
Cycle 1 Day 1	11700 (56.8)
Cycle 1 Day 8	37900 (54)

Adverse Events

Time Frame	Baseline up to 12 Months
Adverse Event Reporting Description	All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Arm/Group Title	Selpercatinib
Arm/Group Description	160 mg Selpercatinib administered orally twice daily (BID).
All Cause Mortality
	Selpercatinib
	Affected / at Risk (%)	# Events
Total	3/77 (3.9%)
Serious Adverse Events
	Selpercatinib
	Affected / at Risk (%)	# Events
Total	17/77 (22.1%)
Endocrine disorders
Cushing's syndrome	1/77 (1.3%)	1
Gastrointestinal disorders
Pancreatitis	1/77 (1.3%)	1
Pancreatitis acute	1/77 (1.3%)	1
General disorders
Pyrexia	2/77 (2.6%)	2
Hepatobiliary disorders
Hepatic function abnormal	3/77 (3.9%)	3
Jaundice	1/77 (1.3%)	1
Liver injury	1/77 (1.3%)	1
Immune system disorders
Hypersensitivity	3/77 (3.9%)	3
Investigations
Alanine aminotransferase increased	2/77 (2.6%)	2
Aspartate aminotransferase increased	3/77 (3.9%)	3
Blood creatinine increased	1/77 (1.3%)	1
Gamma-glutamyltransferase increased	1/77 (1.3%)	1
Platelet count decreased	3/77 (3.9%)	3
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/44 (2.3%)	1
Prostatic obstruction	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Chylothorax	1/77 (1.3%)	1
Interstitial lung disease	1/77 (1.3%)	1
Vascular disorders
Hypertension	1/77 (1.3%)	1
Other (Not Including Serious) Adverse Events
	Selpercatinib
	Affected / at Risk (%)	# Events
Total	75/77 (97.4%)
Blood and lymphatic system disorders
Anaemia	13/77 (16.9%)	14
Leukopenia	5/77 (6.5%)	9
Neutropenia	5/77 (6.5%)	8
Cardiac disorders
Sinus bradycardia	5/77 (6.5%)	6
Sinus tachycardia	6/77 (7.8%)	7
Endocrine disorders
Hypothyroidism	8/77 (10.4%)	11
Thyroid disorder	8/77 (10.4%)	12
Gastrointestinal disorders
Ascites	4/77 (5.2%)	4
Constipation	11/77 (14.3%)	12
Diarrhoea	25/77 (32.5%)	136
Dry mouth	22/77 (28.6%)	23
Nausea	4/77 (5.2%)	5
Vomiting	5/77 (6.5%)	8
General disorders
Chest pain	6/77 (7.8%)	7
Face oedema	5/77 (6.5%)	5
Fatigue	8/77 (10.4%)	9
Oedema peripheral	6/77 (7.8%)	8
Pyrexia	17/77 (22.1%)	22
Swelling face	5/77 (6.5%)	5
Hepatobiliary disorders
Hyperbilirubinaemia	5/77 (6.5%)	9
Immune system disorders
Hypersensitivity	9/77 (11.7%)	9
Investigations
Adenosine deaminase increased	4/77 (5.2%)	4
Alanine aminotransferase increased	50/77 (64.9%)	73
Aspartate aminotransferase increased	47/77 (61%)	83
Bilirubin conjugated increased	20/77 (26%)	34
Blood alkaline phosphatase increased	21/77 (27.3%)	32
Blood bilirubin increased	30/77 (39%)	69
Blood bilirubin unconjugated increased	6/77 (7.8%)	8
Blood creatinine increased	18/77 (23.4%)	30
Blood lactate dehydrogenase increased	18/77 (23.4%)	33
Blood thyroid stimulating hormone increased	9/77 (11.7%)	13
Blood urea increased	5/77 (6.5%)	7
Electrocardiogram qt prolonged	19/77 (24.7%)	34
Electrocardiogram t wave abnormal	10/77 (13%)	12
Electrocardiogram t wave amplitude decreased	5/77 (6.5%)	6
Gamma-glutamyltransferase increased	17/77 (22.1%)	23
Globulins decreased	4/77 (5.2%)	4
Lymphocyte count decreased	9/77 (11.7%)	13
Neutrophil count decreased	20/77 (26%)	41
Platelet count decreased	29/77 (37.7%)	47
Protein total decreased	12/77 (15.6%)	27
Thyroxine increased	5/77 (6.5%)	6
Tri-iodothyronine decreased	5/77 (6.5%)	6
Urine bilirubin increased	5/77 (6.5%)	7
Weight decreased	7/77 (9.1%)	9
Weight increased	18/77 (23.4%)	25
White blood cell count decreased	25/77 (32.5%)	39
Metabolism and nutrition disorders
Decreased appetite	9/77 (11.7%)	9
Hyperglycaemia	12/77 (15.6%)	17
Hyperphosphataemia	11/77 (14.3%)	21
Hyperuricaemia	19/77 (24.7%)	36
Hypoalbuminaemia	26/77 (33.8%)	40
Hypocalcaemia	14/77 (18.2%)	19
Hypochloraemia	4/77 (5.2%)	5
Hypokalaemia	12/77 (15.6%)	20
Hypomagnesaemia	7/77 (9.1%)	9
Hyponatraemia	13/77 (16.9%)	16
Hypophosphataemia	4/77 (5.2%)	6
Renal and urinary disorders
Proteinuria	15/77 (19.5%)	22
Respiratory, thoracic and mediastinal disorders
Cough	4/77 (5.2%)	7
Dyspnoea	7/77 (9.1%)	7
Pleural effusion	4/77 (5.2%)	4
Skin and subcutaneous tissue disorders
Rash	12/77 (15.6%)	13
Vascular disorders
Hypertension	27/77 (35.1%)	42

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.