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

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)

Population: All eligible participants.

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)

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

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)

Population: All eligible participants.

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)

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

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)

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

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)

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

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)

Population: All eligible patients with confirmed response.

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)

Population: All eligible participants with confirmed response.

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

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