. 2022 Aug 15;18(28):3143–3150. doi: 10.2217/fon-2022-0657

Table 2. . Key eligibility criteria for LIBRETTO-531.

Inclusion criteria	Exclusion criteria
Locally advanced or metastatic MTC ○ Histologically confirmed, unresectable locally advanced or metastatic disease and no prior history of treatment with kinase inhibitors for advanced/metastatic disease Patient characteristics ○ Age ≥12, where allowed ○ Documented RECIST 1.1 progression within 14 months by BICR ○ Measurable disease by RECIST 1.1 ○ ECOG performance status of 0–2 ○ Adequate organ function ○ Able to swallow capsules ○ Not pregnant/agreeable to highly effective birth control/no breastfeeding RET alteration ○ RET mutation identified via local NGS or PCR testing on germline DNA, tumor or blood ○ Sufficient tissue for central analysis of RET mutation	Medical conditions ○ An additional validated oncogenic driver in MTC ○ Symptomatic CNS metastases, 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 study treatment or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) >470 msec on more than one ECG during screening ○ 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. ○ Active hemorrhage or at significant risk for hemorrhage Prior/Concomitant Therapy ○ Prior systemic treatment with kinase inhibitor(s) ○ Are taking a concomitant medication that is known to cause QTc prolongation Prior/Concurrent Clinical Study Experience ○ Have participated, within the last 30 days (4 months for studies conducted in Japan; 3 months for studies conducted in the UK), in a clinical study involving an investigational product

Inclusion criteria

Exclusion criteria

Locally advanced or metastatic MTC
○ Histologically confirmed, unresectable locally advanced or metastatic disease and no prior history of treatment with kinase inhibitors for advanced/metastatic disease
Patient characteristics
○ Age ≥12, where allowed
○ Documented RECIST 1.1 progression within 14 months by BICR
○ Measurable disease by RECIST 1.1
○ ECOG performance status of 0–2
○ Adequate organ function
○ Able to swallow capsules
○ Not pregnant/agreeable to highly effective birth control/no breastfeeding
RET alteration
○ RET mutation identified via local NGS or PCR testing on germline DNA, tumor or blood
○ Sufficient tissue for central analysis of RET mutation

Medical conditions
○ An additional validated oncogenic driver in MTC
○ Symptomatic CNS metastases, 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 study treatment or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) >470 msec on more than one ECG during screening
○ 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.
○ Active hemorrhage or at significant risk for hemorrhage
Prior/Concomitant Therapy
○ Prior systemic treatment with kinase inhibitor(s)
○ Are taking a concomitant medication that is known to cause QTc prolongation
Prior/Concurrent Clinical Study Experience
○ Have participated, within the last 30 days (4 months for studies conducted in Japan; 3 months for studies conducted in the UK), in a clinical study involving an investigational product

BICR: Blinded independent committee review; CNS: Central nervous system; ECOG: Eastern Cooperative Oncology Group; MTC: Medullary thyroid cancer; NGS: Next-generation sequencing; PCR: Polymerase chain reaction; RECIST 1.1: Response Evaluation Criteria in Solid Tumors version 1.1.