Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Selpercatinib · 20 trials · 11 indications
EFS by Investigator Assessment in the Primary Analysis Population
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria, or death from any cause in the absence of BICR-documented progressive disease. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
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.
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.
PK: Cmax of Rosuvastatin was reported.
PK: AUC(0-∞) of Rosuvastatin was reported.
PK: AUC\[0-∞\] of Selpercatinib'
PK: AUC\[0-tlast\] of Selpercatinib
PK: Cmax of Selpercatinib.
PK: Cmax of Selpercatinib
PK AUC\[0-∞\] of Selpercatinib
PK: Tmax of Selpercatinib
PK: AUC\[0-tlast\] of Selpercatinib
PK: Cmax of Dabigatran
PK: AUC(0-inf) of Dabigatran
PK: AUC0-t of Selpercatinib. The analysis of variance (ANOVA) model was performed on the natural log (ln)-transformed PK parameters and included calculation of geometric least squares (LS) means and the difference between treatment geometric LS means, as well as their corresponding 90% confidence intervals (CIs). The ratios of geometric LS mean and 90% CI for the ratio of the PK parameter for each comparison was constructed using the exponentiation of the difference and the CIs from the ANOVA analyses.
PK: AUC0-inf of Selpercatinib. The ANOVA model was performed on the natural log (ln)-transformed PK parameters and included calculation of geometric LS means and the difference between treatment geometric LS means, as well as their corresponding 90% CIs. The ratios of geometric LS mean and 90% CI for the ratio of the PK parameter for each comparison was constructed using the exponentiation of the difference and the CIs from the ANOVA analyses.
PK: %AUCextrap of Selpercatinib
PK: Cmax of Selpercatinib. The ANOVA model was performed on the natural log (ln)-transformed PK parameters and included calculation of geometric LS means and the difference between treatment geometric LS means, as well as their corresponding 90% CIs. The ratios of geometric LS mean and 90% CI for the ratio of the PK parameter for each comparison was constructed using the exponentiation of the difference and the CIs from the ANOVA analyses.
PK: Tmax of Selpercatinib
PK: Vz/F of Selpercatinib
PK: CL/F of Selpercatinib
PK: t½ of Selpercatinib
A DLT was any of the adverse events that starts on or after the first administration of study drug listed below, as defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. * Any Grade(G) ≥3 nonhematologic toxicity except G3 fatigue, nausea, tendon reflex decrease, weight gain attributable to normal growth and development. * G3 vomiting/diarrhea was DLT only if it persists \>48 h despite standard of care treatment. * G4 vomiting/diarrhea was DLT regardless of duration. * Any toxicity, regardless of the NCI CTCAE v5.0 grade, resulting in discontinuation or dose reduction of treatment (except symptoms related to progressive disease (PD)). * G4/G3 thrombocytopenia with G1 or higher bleeding. * G4 anemia lasting \>8 days, despite supportive therapy. * G4 neutropenia, lasting \>8 days, despite supportive therapy
ORR: Percentage of participants who achieve best overall response Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST). * CR is defined as disappearance of all target lesions. * PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
The cardiodynamic assessment was performed through 12-lead electrocardiogram (ECG) extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcF. Placebo-corrected change from baseline in QTcF (ΔΔQTcF) was calculated based on model-predicted effect
PK: AUC0-t of Selpercatinib is reported.
PK: AUC%extrap of Selpercatinib is reported.
PK: Cmax of Selpercatinib is reported.
PK: Tmax of Selpercatinib is reported.
PK: Kel of Selpercatinib is reported.
PK: t½ of Selpercatinib is reported.
Data presented are the number of participants who experienced SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and all other non-serious Adverse Event(s) (AEs), regardless of causality, is located in the Reported Adverse Event module.
PK: CL/F of Repaglinide
PK: AUC0-t of Selpercatinib
PK: AUC0-inf of Selpercatinib
PK: Percentage of AUC0-inf extrapolated was calculated as (1 - AUC0-t/AUC0-inf) \* 100.
PK: Cmax of Selpercatinib
PK: Tmax of Selpercatinib
PK: Apparent terminal elimination rate constant; represents the fraction of drug eliminated per unit time calculated by linear least squares regression analysis using the maximum number of points in the terminal log linear phase (e.g., three or more non zero plasma concentrations).
PK: t½ of Selpercatinib.
PK: CL/F of Selpercatinib
PK: Vz/F of Selpercatinib
AUC0-t,u was calculated by multiplying AUC0-t by Fu (i.e., AUC0-t\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.
AUC0-inf,u was calculated by multiplying AUC0-inf by Fu (i.e., AUC0-inf\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.
Cmax,u was calculated by multiplying Cmax by Fu (i.e., Cmax\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.
CL/F,u was calculated by multiplying CL/F by Fu (i.e., CL/F\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.
Vz/F,u was calculated by multiplying Vz/F by Fu (i.e., Vz/F\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.
PK: CumAe was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.
PK: Cum%Dose was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.
PK: CLr of Selpercatinib was reported.The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.
PK: AUC0-t was calculated using the linear trapezoidal rule for increasing and decreasing concentrations.
PK: Area under the plasma concentration time curve extrapolated to infinity, calculated as AUC(0-t) + Ct/λZ, where Ct is the last measurable concentration and λZ is the apparent terminal elimination rate constant.
PK: %AUCextrap of Selpercatinib was reported.
PK: Apparent terminal elimination rate constant, where λZ is the magnitude of the slope of the linear regression of the log concentration versus-time profile during the terminal phase.
PK: Apparent terminal elimination half-life (whenever possible), where t1/2 = natural log (ln)(2)/λZ.
CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC (0-inf), expressed in liter/hour (L/hr).
PK: Vd/F was calculated as CL/F/λZ.
PK: MRT represents the average time the drug (selpercatinib) stays in the body.
PK: AUClast of Selpercatinib in plasma
PK: AUClast of \[14C\] Selpercatinib in plasma and whole blood
PK: AUC0-inf of Selpercatinib in plasma
PK: AUC0-inf of \[14C\] Selpercatinib in plasma and whole blood
PK: AUC0-24 of Selpercatinib in plasma
PK: AUC0-24 of \[14C\] Selpercatinib in plasma and whole blood
PK: Cmax of Selpercatinib in plasma
PK: Cmax of \[14C\] Selpercatinib in plasma and whole blood
PK: Tmax of Selpercatinib in plasma
PK: Tmax of \[14C\] Selpercatinib in plasma and whole blood
PK: t½ of Selpercatinib in plasma
PK: t½ of \[14C\] Selpercatinib in plasma and whole blood
PK: CL/F of Selpercatinib in plasma
PK: Vz/F of Selpercatinib in plasma
PK: AUC0-24 of Selpercatinib in plasma/AUC0-24 of total radioactivity in plasma
PK: AUC0-24 of total radioactivity in whole blood/AUC0-24 of total radioactivity in whole blood
PK: AUClast of Selpercatinib in plasma
PK: AUClast of \[14C\] Selpercatinib in plasma
PK: AUC0-inf of Selpercatinib in plasma
PK: AUC0-inf of \[14C\] Selpercatinib in plasma
PK: Cmax of Selpercatinib in plasma
PK: Cmax of \[14C\] Selpercatinib in plasma
PK: Tmax of Selpercatinib in plasma
PK: Tmax of \[14C\] Selpercatinib in plasma
PK: t½ of Selpercatinib in plasma
PK: t½ of \[14C\] Selpercatinib in plasma
PK: CL/F of Selpercatinib in plasma
PK: CL of \[14C\] Selpercatinib in plasma
PK: Vz/F of Selpercatinib in plasma
PK: Vz of \[14C\] Selpercatinib in plasma
PK: Vss of \[14C\] Selpercatinib in plasma
Absolute bioavailability was determined by comparing the plasma exposure of LOXO-292 following oral dosing with the plasma exposure of \[14C\]-LOXO-292 following IV dosing.
PK: PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam was reported.
PK: PK: AUC0-inf of midazolam and its metabolite 1-OH-midazolam was reported.
PK: PK: AUC%extrap of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Cmax of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Tmax of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Kel of midazolam and its metabolite 1-OH-midazolam was reported.
PK: t½ of midazolam and its metabolite 1-OH-midazolam was reported.
PK: CL/F of midazolam was reported.
PK: Vz/F of midazolam was reported.
PK: AUC0-inf of Selpercatinib was reported.
PK: AUC%extrap of Selpercatinib was reported. Outcome measure timeframe: Parts 1 and 2, Period 1: (Day 1) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. Part 1, Period 2; (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. (contd.)
PK: Kel of Selpercatinib was reported. Outcome measure timeframe: Parts 1 and 2, Period 1: (Day 1) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. Part 1, Period 2; (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. (contd.)
PK: AUC0-24 of Selpercatinib in Part 2 was reported.
| Arm | Type | Description |
|---|---|---|
| Selpercatinib | EXPERIMENTAL | Selpercatinib administered orally. |
| Placebo | PLACEBO_COMPARATOR | Placebo administered orally. |
| Selpercatinib - Treatment A (TRT A) | EXPERIMENTAL | 160 milligram (mg) Selpercatinib administered orally twice daily (BID) continuously in 21-day cycles. |
| Pemetrexed and Platinum with or without Pembrolizumab - (TRT B) | ACTIVE_COMPARATOR | Pemetrexed 500 milligrams per meter squared (mg/m2) administered intravenously (IV) on Day 1, every 3 weeks (Q3W), plus investigator's choice of carboplatin area under the concentration versus time curve 5 (AUC 5 \[maximum dose of 750 mg\] IV), or cisplatin (75 mg/m2 cisplatin IV) on Day 1 Q3W for 4 cycles, plus investigator's choice with or without 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles. |
| Cabozantinib or Vandetanib - Treatment B (TRT B) | ACTIVE_COMPARATOR | 140 mg Cabozantinib administered orally daily (QD) or 300 mg Vandetanib administered orally QD per physician choice. Cabozantinib Adolescent Dose: 40 mg/m2. Vandetanib Adolescent Dose: * 0.7 - \<0.9 - 100 mg every other day (QOD) * 0.9 - \<1.2 - 100 mg QD * 1.2 - \<1.6 - 7-day schedule 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - 200 mg - 100 mg * ≥1.6 - 200 QD |
| Rosuvastatin + Selpercatinib | EXPERIMENTAL | Participants received 20 milligram (mg) of rosuvastatin administered orally on Day 1, followed by 20 mg of rosuvastatin coadministered orally with 160 mg of selpercatinib on Day 5. |
| Selpercatinib (Fasted/Fed) | EXPERIMENTAL | Period 1: 160 milligrams (mg) Selpercatinib administered orally on Day 1 in fasted state. Period 2: 160 mg Selpercatinib administered orally on Day 8 in fed state. |
| Selpercatinib (Fed/Fasted) | EXPERIMENTAL | Period 1: 160 mg Selpercatinib administered orally on Day 1 in fed state. Period 2: 160 mg Selpercatinib administered orally on Day 8 in fasted state. |
| Selpercatinib Sequence A: | EXPERIMENTAL | Period 1: 20 milligram (mg) Selpercatinib capsule single oral dose administered orally on Day 1. Period 2: 20 mg per milliliter (mL) Selpercatinib Powder for Oral suspension (PFOS) single oral suspension dose on Day 8. Period 3: 20 mg/mL Selpercatinib Ready to Use (RTU) single oral suspension on Day 15. |
| Selpercatinib Sequence B | EXPERIMENTAL | Period 1: 20 mg/mL Selpercatinib RTU single oral suspension on Day 1. Period 2: 20 mg Selpercatinib capsule single oral dose administered orally on Day 8. Period 3: 20 mg/mL PFOS single oral suspension dose on Day 15. |
| Selpercatinib Sequence C | EXPERIMENTAL | Period 1: 20 mg/mL PFOS single oral suspension dose on Day 1. Period 2: 20 mg/mL Selpercatinib RTU single oral suspension on Day 8. Period 3: 20 mg Selpercatinib capsule single oral dose administered orally on Day 15. |
| Selpercatinib (Test) | EXPERIMENTAL | 160 mg Selpercatinib (tablet formulation) given orally on days 1 and 15. |
| Selpercatinib (Reference) | ACTIVE_COMPARATOR | 160 mg Selpercatinib (2 X 80 mg capsule formulation) given orally on days 1 and 15. |
| Dabigatran + Selpercatinib | EXPERIMENTAL | Participants received a single oral dose of 150 milligrams (mg) dabigatran on Day 1 and a single oral dose of 150 mg dabigatran coadministered with a single oral dose of 2 x 80 mg (160 mg) selpercatinib on Day 8. There was a washout period of 7 days between dosing on Days 1 and 8. |
| 160 milligram (mg) Selpercatinib | EXPERIMENTAL | Participants received a single oral dose of 160 mg Selpercatinib (Study Day 1). |
| 150 mg Ranitidine dosed with 160 mg Selpercatinib | EXPERIMENTAL | Participants received 150 mg ranitidine twice a day orally for 11 days (Study Days 8 to 18) with a single oral dose of 160 mg Selpercatinib (Study Day 12). |
| 40 mg Omeprazole dosed with 160 mg Selpercatinib | EXPERIMENTAL | Participants received 40 mg omeprazole once daily for 11 days (Study Days 19 to 29) with a single oral dose of 160 mg Selpercatinib (Study Day 23). |
| Cohort 1: Medullary Thyroid Cancer (MTC) Group | EXPERIMENTAL | Participants in this cohort had MTC and received 160 mg of selpercatinib BID orally on Days 1 through 28 of a 28-day cycle. The treatment was continued until participants experienced a progressive disease, unacceptable toxicity, or other protocol-defined reason for discontinuation. |
| Cohort 2: Papillary Thyroid Cancer (PTC) Group | EXPERIMENTAL | Participants in this cohort had PTC and received 160 mg of selpercatinib BID orally on Days 1 through 28 of a 28-day cycle. The treatment was continued until participants experienced a progressive disease, unacceptable toxicity, or other protocol-defined reason for discontinuation. |
| Cohort 3: Other Cancer Group | EXPERIMENTAL | Participants in this cohort had other (REarranged during Transfection (RET)-altered non-thyroid) cancer and received 160 mg of selpercatinib BID orally on Days 1 through 28 of a 28-day cycle. The treatment was continued until participants experienced a progressive disease, unacceptable toxicity, or other protocol-defined reason for discontinuation. |
| Treatment Sequence 1: ABCD | EXPERIMENTAL | Period 1: 320 milligram (mg) Selpercatinib and Selpercatinib matching placebo (Treatment A) Period 2: 640 mg Selpercatinib (Treatment B) Period 3: 400 mg moxifloxacin (Treatment C) Period 4: Selpercatinib matching placebo (Treatment D) Participants received their assigned treatments in each of the above treatment period on Day 1 orally. |
| Treatment Sequence 2: BDAC | EXPERIMENTAL | Period 1: 640 mg Selpercatinib (Treatment B) Period 2: Selpercatinib matching placebo (Treatment D) Period 3: 320 mg Selpercatinib and Selpercatinib matching placebo (Treatment A) Period 4: 400 mg moxifloxacin (Treatment C) Participants received their assigned treatments in each of the above treatment period on Day 1 orally. |
| Treatment Sequence 3: CADB | ACTIVE_COMPARATOR | Period 1: 400 mg moxifloxacin (Treatment C) Period 2: Selpercatinib matching placebo (Treatment D) Period 3: 320 mg Selpercatinib and Selpercatinib matching placebo (Treatment A) Period 4: 640 mg Selpercatinib (Treatment B) Participants received their assigned treatments in each of the above treatment period on Day 1 orally. Period Title: Treatment Period 1 |
| Treatment Sequence 4: DCBA | PLACEBO_COMPARATOR | Period 1: Selpercatinib matching placebo (Treatment D) Period 2: 400 mg moxifloxacin (Treatment C) Period 3: 640 mg Selpercatinib (Treatment B) Period 4: 320 mg Selpercatinib and Selpercatinib matching placebo (Treatment A) Participants received their assigned treatments in each of the above treatment period on Day 1 orally. |
| 320 mg Selpercatinib | EXPERIMENTAL | Participants received a single oral dose of 320 mg selpercatinib on Day 1, preceded by an overnight fast of at least 10 hours, followed by a fast from food (not including water) for at least 4 hours post dose. |
| 640 mg Selpercatinib | EXPERIMENTAL | Participants received a single oral dose of 640 mg selpercatinib on Day 1, preceded by an overnight fast of at least 10 hours, followed by a fast from food (not including water) for at least 4 hours post dose. |
| 720 mg Selpercatinib | EXPERIMENTAL | Participants received a single oral dose of 720 mg selpercatinib on Day 1, preceded by an overnight fast of at least 10 hours, followed by a fast from food (not including water) for at least 4 hours post dose. |
| Period 1: Repaglinide | EXPERIMENTAL | * Day 1: Participants received single dose of 0.5 mg repaglinide tablet. |
| Period 2: Selpercatinib + Repaglinide | EXPERIMENTAL | * Day 1 to Day 9: Participants received 160 mg Selpercatinib capsule twice daily (BID). * Day 10: Participant received 160 mg Selpercatinib capsules BID co-administered with a single oral dose of 0.5 mg Repaglinide tablet on the morning of Day 10. |
| Selpercatinib (Control; Normal Renal Function) | EXPERIMENTAL | Participants with normal renal function (estimated glomerular filtration rate greater than or equal to \[eGFR ≥ 90 milliliters per minute (mL/min) per 1.73 square meters (m²)\] received a single 160 milligrams (mg) oral dose of Selpercatinib on Day 1, administered in a fasted state. |
| Selpercatinib (Mild Renal Impairment) | EXPERIMENTAL | Participants with mild renal impairment (eGFR between 60 and 90 mL/min/1.73 m²) received a single 160 mg oral dose of Selpercatinib on Day 1, administered in a fasted state. |
| Selpercatinib (Moderate Renal Impairment) | EXPERIMENTAL | Participants with moderate renal impairment (eGFR between 30 and 60 mL/min/1.73 m²) received a single 160 mg oral dose of Selpercatinib on Day 1, administered in a fasted state. |
| Selpercatinib (Severe Renal Impairment) | EXPERIMENTAL | Participants with severe renal impairment (eGFR less than (\<) 30 mL/min/1.73 m² and not requiring hemodialysis) received a single 160 mg oral dose of Selpercatinib on Day 1, administered in a fasted state. |
| 160 milligram (mg) Selpercatinib: Normal Hepatic Function | EXPERIMENTAL | 160 mg selpercatinib administered orally to healthy participants after at least a 2-hour fast on Day 1. |
| 160 mg Selpercatinib: Mild Hepatic Impairment | EXPERIMENTAL | 160 mg selpercatinib administered orally to participants with mild hepatic impairment per Child-Pugh \[CP\] classification (CP Class A, score of 5 or 6) after at least a 2-hour fast on Day 1. |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | EXPERIMENTAL | 160 mg selpercatinib administered orally to participants with moderate hepatic impairment per CP classification (CP Class B, score of 7 to 9) after at least a 2-hour fast on Day 1. |
| 160 mg Selpercatinib: Severe Hepatic Impairment | EXPERIMENTAL | 160 mg Selpercatinib administered orally to participants with severe hepatic impairment per CP classification (CP Class C, score of 10 to 15) after at least a 2-hour fast on Day 1. |
| Carbon-14-labelled [14C]-Selpercatinib - Part 1 | EXPERIMENTAL | Participants received a single oral dose of 165 milligram (mg) of \[14C\]-Selpercatinib (containing approximately 40 µCi). |
| Selpercatinib and [14C]-Selpercatinib - Part 2 | EXPERIMENTAL | Participants received a single oral dose of 160 mg Selpercatinib followed by single dose of \<100 µg of \[14C\]-Selpercatinib (containing approximately 1 µCi) administered intravenously (IV). |
| Period 1: Midazolam | EXPERIMENTAL | * Day 1: Participants received single oral dose of 2 milligram (mg) midazolam syrup. |
| Period 2: Selpercatinib + Midazolam | EXPERIMENTAL | * Day 1 to Day 9: Participants received 160 mg Selpercatinib capsules twice daily (BID). * Day 10: Participant received 160 mg Selpercatinib capsules BID co-administered with a single oral dose of 2 mg midazolam syrup on the morning of Day 10. |
| Treatment Sequence 2: ABDC | EXPERIMENTAL | Participants received: * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 1 in fasted state. * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 2 in fed state. * Multiple daily oral doses of 40 mg omeprazole administered on Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 3 in fed state. * Multiple daily oral doses of 40 mg omeprazole administered on Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 4 in fasted state. Periods 1 and 2, 2 and 3 were separated by a 7-day washout period. There was no washout between Periods 3 and 4. |
| Treatment Sequence 3: BACD | EXPERIMENTAL | Participants received: * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 1 in fed state. * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 2 in fasted state. * Multiple daily oral doses of 40 mg omeprazole administered on Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 3 in fasted state. * Multiple daily oral doses of 40 mg omeprazole administered on Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 4 in fed state. Periods 1 and 2, 2 and 3 were separated by a 7-day washout period. There was no washout between Periods 3 and 4. |
| Treatment Sequence 4: BADC | EXPERIMENTAL | Participants received: * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 1 in fed state. * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 2 in fasted state. * Multiple daily oral doses of 40 mg omeprazole administered on Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 3 in fed state. * Multiple daily oral doses of 40 mg omeprazole administered on Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 4 in fasted state. Periods 1 and 2, 2 and 3 were separated by a 7-day washout period. There was no washout between Periods 3 and 4. |
| Part 1 - 160 mg Selpercatinib + 200 mg Itraconazole | EXPERIMENTAL | Participants received a single oral dose of 160 milligrams (mg) selpercatinib on Day 1 of Period 1. In Period 2, participants received an oral dose of 200 mg itraconazole administered once daily (QD) for 11 consecutive days (Days -4 to 7) with a single oral dose of 160 mg selpercatinib co-administered on Day 1 of Period 2. There was a washout period of at least 7 days between the dose of selpercatinib in Period 1 and the first dose of itraconazole in Period 2. |
| Part 2 - 160 mg Selpercatinib + 600 mg Rifampin | EXPERIMENTAL | Participants received a single oral dose of 160 mg selpercatinib on Day 1 of Period 1. In Period 2, participants received an oral dose of 600 mg rifampin administered QD for 16 consecutive days (Days 1 to 16) with a single oral dose of 160 mg selpercatinib co-administered on Day 1 and Day 10 of Period 2. There was a washout period of at least 7 days between the dose of selpercatinib in Period 1 and the first dose of rifampin and selpercatinib in Period 2. |
| Name | Type | Description |
|---|---|---|
| Selpercatinib | DRUG | Administered orally. |
| Placebo | DRUG | Administered orally. |
| Carboplatin | DRUG | Administered IV |
| Cisplatin | DRUG | Administered IV |
| Pemetrexed | DRUG | Administered IV |
| Pembrolizumab | DRUG | Administered IV |
| Cabozantinib | DRUG | Administered orally |
| Vandetanib | DRUG | Administered orally |
| Rosuvastatin | DRUG | Administered orally. |
| Dabigatran | DRUG | Administered orally. |
| Ranitidine | DRUG | Administered orally. |
| Omeprazole | DRUG | Administered orally. |
| Moxifloxacin | DRUG | Administered orally |
| Repaglinide | DRUG | Administered orally. |
| [14C]-Selpercatinib | DRUG | Administered as an oral solution |
| Midazolam | DRUG | Administered orally. |
| Itraconazole | DRUG | Administered orally. |
| Rifampin | DRUG | Administered orally. |
Inclusion Criteria: * Must have histologically confirmed Stage IB, II, or IIIA NSCLC. * Must have an activating RET gene fusion in tumor based on polymerase chain reaction (PCR), next generation sequencing (NGS), or another molecular test per sponsor's approval. * Must have received definitive loco...