INLURIYO is indicated: as monotherapy, for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 (ESR1 )-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy [see Dosage and Administration ( 2.1 )] . in combination with abema...
Select patients for treatment of ER-positive, HER2-negative advanced or metastatic breast cancer with INLURIYO based on the presence of ESR1 mutation(s) in a plasma specimen using an FDA-authorized test [see Indications and Usage ( 1 ) and Clinical Studies ( 14 )] . Information on FDA-authorized tests for the detection of ESR1 mutations in breast cancer is available at: https://www.fda.gov/CompanionDiagnostics. Th...
How Supplied INLURIYO 200 mg tablets are white, film coated, capsule-shaped tablets with “LILLY” on one side and “1717” and an elongated 4-point starburst on the other side. INLURIYO 200 mg tablets are supplied in either a 28-count or 56-count bottle configuration. 28-count: NDC 0002-1717-28 56-count: NDC 0002-1717-56 Storage and Handling Store at 20°C to 25°C (68°F to 77°F). Excursions between 15°C to 30°C (59°F ...
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www.INLURIYO.comINLURIYO is indicated:
Select patients for treatment of ER-positive, HER2-negative advanced or metastatic breast cancer with INLURIYO based on the presence of ESR1 mutation(s) in a plasma specimen using an FDA-authorized test [see Indications and Usage (1) and Clinical Studies (14)].
Information on FDA-authorized tests for the detection of ESR1 mutations in breast cancer is available at: www.fda.gov/CompanionDiagnostics.
The recommended dosage of INLURIYO, as monotherapy or in combination with abemaciclib, is 400 mg orally once daily until disease progression or unacceptable toxicity.
Take on an empty stomach at least 2 hours before food or 1 hour after food [see Clinical Pharmacology (12.3)]. Take INLURIYO tablets at approximately the same time daily. Swallow the tablets whole. Do not split, crush, or chew the tablets.
If patient misses a dose by 6 or more hours or vomits, instruct the patient to take the next dose the following day at its scheduled time.
Refer to the Prescribing Information for the recommended dosage of abemaciclib when used in combination with INLURIYO.
The recommended INLURIYO dosage modifications for adverse reactions are provided in Tables 1 and 2.
The recommended dose reduction is to 200 mg once daily.
Permanently discontinue INLURIYO in patients who are unable to tolerate 200 mg once daily.
Refer to the Prescribing Information for dosage modification guidelines and other relevant safety information for abemaciclib when used in combination with INLURIYO.
| Grade | INLURIYO Dosage Modifications |
| Persistent or recurrent Grade 2 that does not resolve with maximal supportive measures within 7 days to baseline or Grade 1 | Withhold until toxicity resolves to baseline or ≤Grade 1. Resume INLURIYO at the same dose. |
| Grade 3 or 4 (except non-hepatic asymptomatic laboratory changes) | Withhold until toxicity resolves to baseline or ≤Grade 1. Resume INLURIYO at next lower dose. |
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| Monitor ALT/AST during imlunestrant therapy as clinically indicated. | |
| Liver Transaminase | INLURIYO Dosage Modifications |
| Persistent or Recurrent: AST/ALT >3.0-5.0×ULN | Withhold until toxicity resolves to baseline or to >ULN-3.0×ULN. Resume INLURIYO at the same dose. |
| If AST/ALT at baseline is within the normal range: AST/ALT >5.0-20×ULN Or If AST/ALT at baseline is above ULN: AST/ALT ≥3 × baseline (if AST/ALT≥1.5 x ULN at baseline) Or AST/ALT >8 × ULN (whichever is the lower threshold) | Withhold until toxicity resolves to baseline or to >ULN-3.0×ULN. Resume INLURIYO at next lower dose or discontinue if receiving 200 mg daily. |
| AST/ALT >20.0×ULN Or ALT or AST ≥ 3 × ULN concurrent with TBL ≥ 2 × ULN (if ALT or AST < 1.5 × ULN at baseline), in the absence of cholestasis Or ALT or AST ≥ 2 × baseline concurrent with TBL ≥ 2 × ULN (if ALT or AST ≥ 1.5 × ULN at baseline), in the absence of cholestasis | Permanently discontinue INLURIYO. |
The recommended dosage of INLURIYO for patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment is 200 mg once daily. Monitor for increased adverse reactions [see Clinical Pharmacology (12.3)].
Refer to the Prescribing Information for dosage modification for severe hepatic impairment for abemaciclib when used in combination with INLURIYO.
Strong CYP3A Inhibitors
Avoid concomitant use with strong CYP3A inhibitors. If concomitant use cannot be avoided, decrease the INLURIYO dosage to 200 mg once daily [see Drug Interactions (7.1)].
Refer to the Prescribing Information for dosage modification for strong CYP3A Inhibitors for abemaciclib when used in combination with INLURIYO.
Strong CYP3A Inducers
Avoid concomitant use with strong CYP3A inducers. If concomitant use cannot be avoided, increase the INLURIYO dosage to 600 mg once daily [see Drug Interactions (7.1)].
INLURIYO tablets contain 200 mg imlunestrant and are white, film coated-capsule-shaped tablets, with “LILLY” on one side and “1717” and elongated 4-point starburst on the other side.
None.
Based on findings in animals and its mechanism of action, INLURIYO can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, oral administration of imlunestrant to pregnant rats during the period of organogenesis led to embryo-fetal mortality and structural abnormalities at maternal exposures that were below the human exposure at the recommended dose based on AUC.
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with INLURIYO and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with INLURIYO and for 1 week after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
ER+, HER2-, ESR1-mutated Advanced or Metastatic Breast Cancer
INLURIYO as Monotherapy
The safety of INLURIYO was evaluated in 651 patients with ER+, HER2- locally advanced or metastatic breast cancer previously treated with endocrine therapy with or without a prior CDK4/6 inhibitor in EMBER-3 [see Clinical Studies (14)]. Patients received INLURIYO 400 mg orally, once daily (n=327), or standard of care (n=324) consisting of either fulvestrant (n=292) or exemestane (n=32). Among patients who were treated with INLURIYO, the median duration of exposure was 5.6 months (range: 0.2 to 28.6 months) in EMBER-3.
Serious adverse reactions occurred in 10% of patients who received INLURIYO. Serious adverse reactions in > 1% of patients included pleural effusion (1.2%). Fatal adverse reactions occurred in 1.8% of patients who received INLURIYO, including cardiac arrest, acute myocardial infarction, right ventricular failure, hypovolemic shock, and upper gastrointestinal hemorrhage (each 0.3%).
Permanent treatment discontinuation of INLURIYO due to an adverse reaction occurred in 4.6% of patients. Adverse reactions which resulted in permanent discontinuation of INLURIYO included increased alanine aminotransferase (ALT) (0.9%), abdominal pain, fatigue, fractured sacrum, hepatotoxicity, neuropathy peripheral, and pyrexia (each 0.3%).
Dosage interruption of INLURIYO due to an adverse reaction occurred in 10% of patients. Adverse reactions which required dosage interruption in >0.5% were vomiting (1.5%); increased aspartate aminotransferase (AST), and COVID-19 (each 0.9%); and increased ALT, anemia, diarrhea, decreased neutrophil count, and pyrexia (each 0.6%).
Dose reductions of INLURIYO due to an adverse reaction occurred in 2.4% of patients. Adverse reactions which required dose reductions were increased AST (0.6%); and increased ALT, anemia, fatigue, interstitial lung disease, nausea, neutropenia, and vomiting (each 0.3%).
The most common (≥10%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin, musculoskeletal pain, decreased calcium, decreased neutrophils, increased AST, fatigue, diarrhea, increased ALT, increased triglycerides, nausea, decreased platelets, constipation, increased cholesterol, and abdominal pain.
Table 3 summarizes the adverse reactions in EMBER-3.
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| Adverse Reactiona | INLURIYO N=327 | Fulvestrant or Exemestane N=324 | ||
| All Grades % | Grades 3 or 4 % | All Grades % | Grades 3 or 4 % | |
| Musculoskeletal Disorders | ||||
| Musculoskeletal Pain | 30 | 3.7 | 29 | 1.9 |
| General Disorders and Administration Site Conditions | ||||
| Fatigueb | 23 | 0.3 | 14 | 0.6 |
| Gastrointestinal Disorders | ||||
| Diarrhea | 22 | 0.6 | 12 | 0.0 |
| Nausea | 17 | 0.3 | 13 | 0.0 |
| Constipation | 10 | 0 | 6 | 0.3 |
| Abdominal painb | 10 | 0.3 | 6 | 0.6 |
Clinically relevant adverse reactions (<10%) in patients who received INLURIYO included: vomiting (9%), headache (9%), cough (9%), decreased appetite (8%), hot flush (7%), pruritus (3.7%), dyspepsia (2.8%), and stomatitis (2.4%).
Table 4 summarizes the laboratory abnormalities in EMBER-3.
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| Lab Abnormalitya | INLURIYOb | Fulvestrant or Exemestaneb | ||
| All Grades % | Grades 3 or 4 % | All Grades % | Grades 3 or 4 % | |
| Hematology | ||||
| Hemoglobin decreased | 30 | 1.2 | 35 | 3.4 |
| Neutrophils decreased | 26 | 4 | 29 | 4.7 |
| Platelets decreased | 16 | 1.8 | 14 | 1.3 |
| Chemistry | ||||
| Calcium decreased | 26 | 0 | 19 | 0.6 |
| AST increased | 25 | 1.9 | 27 | 2.3 |
| ALT increased | 21 | 1.3 | 23 | 1.0 |
| Triglycerides increased | 21 | 0 | 22 | 1.2 |
| Cholesterol increased | 10 | 0 | 12 | 0 |
INLURIYO in Combination with Abemaciclib
The safety of INLURIYO in combination with abemaciclib was evaluated in 535 patients with ER+, HER2- locally advanced or metastatic breast cancer previously treated with endocrine therapy with or without a prior CDK4/6 inhibitor in EMBER-3 [see Clinical Studies (14)]. Patients received INLURIYO 400 mg orally once daily in combination with abemaciclib 150 mg twice daily (N=208), or INLURIYO monotherapy 400 mg, once daily (n=327). Among patients who were treated with INLURIYO in combination with abemaciclib, the median duration of exposure was 7.7 months (range 1 day to 25.3 months).
Serious adverse reactions occurred in 21% of patients who received INLURIYO in combination with abemaciclib. Serious adverse reactions in >1% of patients included pneumonia (2.4%), abdominal pain, and renal failure (each 1.4%). Fatal adverse reactions occurred in 3.8% of patients who received INLURIYO in combination with abemaciclib, including pneumonia (1.4%), myocardial infarction, interstitial lung disease, and sepsis (0.5% each).
Permanent treatment discontinuation of INLURIYO due to an adverse reaction occurred in two patients (1%). The adverse reactions which required permanent discontinuation were increased ALT and anemia (0.5% each).
Dosage interruptions of INLURIYO due to an adverse reaction occurred in 50% of patients. Adverse reactions which required dosage interruptions of INLURIYO in ≥2% of patients included diarrhea (14%), neutropenia (9%), decreased neutrophil count (6%), nausea (6%), anemia (6%), increased ALT (2.4%), and vomiting (2.4%).
Dose reductions of INLURIYO due to an adverse reaction occurred in 18% of patients. Adverse reactions which required dose reductions of INLURIYO in ≥ 1% of patients included diarrhea (6%), neutropenia (1.9%), nausea (1.9%), increased ALT (1.9%), and decreased neutrophil count (1.4%).
The most common (≥10%) adverse reactions, including laboratory abnormalities, were decreased neutrophils, diarrhea, decreased hemoglobin, decreased lymphocytes, nausea, decreased platelets, fatigue, increased triglycerides, infections, increased AST, increased creatinine, increased ALT, vomiting, musculoskeletal pain, abdominal pain, decreased appetite, increased cholesterol, rash, cough, headache, and decreased weight.
Table 5 summarizes the adverse reactions in EMBER-3.
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| Adverse Reactiona | INLURIYO plus Abemaciclib N=208 | INLURIYO N=327 | ||
| All Grades % | Grades 3 or 4 % | All Grades % | Grades 3 or 4 % | |
| Gastrointestinal Disorders | ||||
| Diarrhea | 86 | 9 | 23 | 0.3 |
| Nausea | 51 | 1.9 | 18 | 0.3 |
| Vomiting | 32 | 0.5 | 10 | 0.6 |
| Abdominal painb | 24 | 1.9 | 11 | 0.3 |
| General Disorders and Administration Site Conditions | ||||
| Fatigueb | 41 | 5 | 24 | 0.3 |
| Infections and Infestations | ||||
| Infectionsb | 36 | 7 | 25 | 3.4 |
| Musculoskeletal Disorders | ||||
| Musculoskeletal painb | 25 | 1.4 | 31 | 2.8 |
| Metabolism and Nutrition Disorders | ||||
| Decreased appetiteb | 22 | 1 | 9 | 0.3 |
| Skin and Subcutaneous Tissue Disorders | ||||
| Rashb | 14 | 1.4 | 4.9 | 0 |
| Respiratory, Thoracic and Mediastinal Disorders | ||||
| Coughb | 13 | 0 | 9 | 0 |
| Nervous System Disorders | ||||
| Headacheb | 10 | 0.5 | 9 | 0 |
| Investigations | ||||
| Weight decreased | 10 | 0 | 4.6 | 0 |
Clinically relevant adverse reactions (<10%) in patients who received INLURIYO in combination with abemaciclib included: constipation (9%), stomatitis (9%), fever (9%), urinary tract infection (8%), dizziness (8%), hot flush (6%), insomnia (6%), arrhythmia (6%), alopecia (5%), back pain (4.8%), venous thromboembolic event (4.8%) and interstitial lung disease or pneumonitis (2.9%).
Table 6 summarizes the laboratory abnormalities in EMBER-3.
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| Lab Abnormalitya | INLURIYO plus Abemaciclib b | INLURIYOb | ||
| All Grades % | Grades 3 or 4 % | All Grades % | Grades 3 or 4 % | |
| Hematology | ||||
| Neutrophils decreased | 86 | 21 | 28 | 4.3 |
| Hemoglobin decreased | 81 | 9 | 34 | 2.2 |
| Lymphocytes decreased | 58 | 9 | 29 | 2.2 |
| Platelets decreased | 48 | 2.4 | 18 | 2.8 |
| Chemistry | ||||
| Triglycerides increased | 40 | 2.3 | 22 | 0 |
| AST increased | 36 | 2.5 | 27 | 1.9 |
| Creatinine increased | 36 | 1.1 | 6 | 0.3 |
| ALT increased | 33 | 5 | 22 | 1.3 |
| Cholesterol increased | 18 | 0 | 12 | 0.4 |
Strong CYP3A Inhibitors
Avoid concomitant use of INLURIYO with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce the dosage of INLURIYO [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)].
Imlunestrant is a CYP3A substrate. Concomitant use of a strong CYP3A inhibitor increases imlunestrant exposure [see Clinical Pharmacology (12.3)], which may increase the risk of INLURIYO-associated adverse reactions.
Strong CYP3A Inducers
Avoid concomitant use of INLURIYO with strong CYP3A inducers. If concomitant use cannot be avoided, increase the dosage of INLURIYO [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)].
Imlunestrant is a CYP3A substrate. Concomitant use of a strong CYP3A inducer decreases imlunestrant exposure [see Clinical Pharmacology (12.3)], which may reduce effectiveness of INLURIYO.
P-gp or BCRP Substrates
Avoid concomitant use unless otherwise recommended in the Prescribing Information for P-gp or BCRP substrates where minimal concentration changes may lead to serious adverse reactions.
Imlunestrant inhibits both P-gp and BCRP. Imlunestrant increases exposure of P-gp and BCRP substrates, which may increase the risk of adverse reactions related to these substrates [see Clinical Pharmacology (12.3)].
Risk Summary
Refer to the Prescribing Information of abemaciclib when administered in combination with INLURIYO for pregnancy information.
Based on findings in animals and its mechanism of action, INLURIYO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available human data on INLURIYO use in pregnant women to inform the drug-associated risk. In an animal reproduction study, oral administration of imlunestrant to pregnant rats during the period of organogenesis led to embryo-fetal mortality and structural abnormalities at maternal exposures below the human exposure at the recommended dose based on AUC (see Data). Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies.
Data
Animal Data
In an embryo-fetal development study, imlunestrant was administered orally to pregnant rats during the period of organogenesis from gestation day 6 to 17 at doses of 0.3, 3, and 30 mg/kg/day. Imlunestrant caused embryo-fetal mortality (increased resorption, reduced number of live fetuses) at ≥0.3 mg/kg/day, approximately 0.1 times the human AUC at the recommended dose. Early delivery, fetal malformations (including small jaw, protruding tongue, malrotated, and hyperextended hindlimb) and fetal variations (edema localized subcutis) were observed at ≥3 mg/kg/day, approximately 1 time the human AUC at the recommended dose.
Refer to the Prescribing Information of abemaciclib when administered in combination with INLURIYO for lactation information. When used in combination, advise patients to not breastfeed during treatment and for the longest post-treatment duration recommended in the Prescribing Information of the individual products.
Risk Summary
There are no data on the presence of imlunestrant or its metabolites in human milk, its effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise lactating women to not breastfeed during treatment with INLURIYO and for 1 week after the last dose.
Refer to the Prescribing Information of abemaciclib when administered in combination with INLURIYO for contraception and infertility information. When used in combination, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of the individual products.
INLURIYO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy Testing
Verify the pregnancy status in females of reproductive potential prior to initiating INLURIYO.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with INLURIYO and for 1 week after the last dose.
Males
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with INLURIYO and for 1 week after the last dose.
Infertility
Based on findings in animals, INLURIYO may impair fertility in females and males of reproductive potential. Findings in animals were reversible [see Nonclinical Toxicology (13.1)].
The safety and effectiveness of INLURIYO have not been established in pediatric patients.
Of 327 patients who received INLURIYO monotherapy in the EMBER-3 study, 118 patients were ≥ 65 years of age and 37 patients were ≥ 75 years of age. No overall differences in safety or effectiveness of INLURIYO monotherapy have been observed between patients 65 years of age and older and younger adult patients.
Of the 208 patients who received INLURIYO in combination with abemaciclib in the EMBER-3 study, 90 patients were ≥65 years of age and 27 patients were ≥75 years of age. There was a higher rate of nausea in patients aged 65 years or older (59%) compared with younger patients (44%). The EMBER-3 study did not include sufficient numbers of patients 65 years of age and older with ESR1 mutations treated with INLURIYO in combination with abemaciclib to determine whether they respond differently than younger patients.
INLURIYO tablets contain imlunestrant, an estrogen receptor antagonist. The chemical name for imlunestrant tosylate is (5R)-5-(4-(2-(3-(fluoromethyl)azetidin-1-yl)ethoxy)phenyl)-8-(trifluoromethyl)-5H-(1)benzopyrano(4,3-c)quinolin-2-ol, tosylate salt (1:1). Imlunestrant tosylate is a white to practically white to yellow powder with the empirical formula C29H24F4N2O3.C7H8O3S and a molecular weight 696.71 g/mol. The aqueous solubility of imlunestrant tosylate is slightly soluble at low pH, insoluble at neutral pH, and sparingly soluble at high pH. The chemical structure of imlunestrant tosylate is shown below:
INLURIYO tablets are for oral administration. Each INLURIYO tablet is available as capsule-shaped, film-coated tablet that contains 200 mg imlunestrant (equivalent to 265.66 mg imlunestrant tosylate). The tablet contains the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and microcrystalline cellulose. The tablets are coated using a common white coating, which consists of polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
Imlunestrant is an estrogen receptor (ER) antagonist that binds to ERα. In vitro, imlunestrant induced degradation of ERα, leading to inhibition of ER-dependent gene transcription and cellular proliferation in ER+ breast cancer cells. Imlunestrant demonstrated in vitro and in vivo anti-tumor activity in ER+ breast cancer xenograft models, including models with ESR1 mutations.
Imlunestrant exposure-response relationships and the time course of pharmacodynamics have not been fully characterized.
Cardiac Electrophysiology
At 2 times the mean maximum concentration observed with the approved recommended dose, a mean increase in the QTc interval >20 msec was not observed.
Imlunestrant pharmacokinetics were observed at steady state at the approved recommended dosage and are presented as mean (%CV) unless otherwise specified. The maximum concentration (Cmax) of imlunestrant is 141 ng/mL (45%) and the area under the concentration-time curve (AUC) is 2,400 ng*h/mL (46%). Imlunestrant Cmax and AUC increase in a dose proportional manner over a dosage range of 200 mg to 1,200 mg (0.5 to 3 times the approved recommended dosage) once daily. Steady-state is reached in approximately 6 days and the accumulation is 2.3-fold based on AUC.
Absorption
Imlunestrant absolute oral bioavailability after a single oral 400 mg dose is 10% (32%). Imlunestrant median (min, max) time to maximum plasma concentration (Tmax) is 4 (2, 8) hours.
Effect of Food
Imlunestrant AUC increased 2-fold and Cmax increased 3.6-fold following administration with a low-fat meal (approximately 475 calories with 13% fat, 16% protein, and 71% carbohydrates). The effect of high-fat meal (approximately 800-1,000 calories with 500-600 calories from fat) on imlunestrant exposures is unknown.
Distribution
The apparent (oral) volume of distribution is 8,120 L (69%). Imlunestrant protein binding is >99% and is not concentration dependent.
Elimination
Imlunestrant elimination half-life is 30 hours with an estimated apparent clearance of 166 L/h (51%).
Metabolism
Imlunestrant is metabolized by sulfation, CYP3A4, and direct glucuronidation (UGT1A1, 1A3, 1A8, 1A9, 1A10).
Excretion
After a single dose of radiolabeled imlunestrant 400 mg to healthy subjects, 97% of the dose was recovered in feces (62% unchanged) and 0.3% in urine.
Specific Populations
No clinically significant differences in the pharmacokinetics of imlunestrant based on age (28 to 95 years), race (64% White, 23% Asian, and 5% Black or African American), ethnicity (74% non-Hispanic/Latino, 17% Hispanic/Latino), body weight (36 to 145 kg), mild to moderate (eGFR 30 to 89 mL/min, estimated by CKD-EPI equation) renal impairment, or UGT1A1 genetic polymorphisms (e.g., UGT1A1*1/*28 or UGT1A1*28/*28). The effect of severe (eGFR 15 to 29 mL/min) renal impairment and renal impairment requiring dialysis on imlunestrant pharmacokinetics is unknown.
Patients with Hepatic Impairment
Imlunestrant AUC increased 2.2-fold in subjects with moderate hepatic impairment (Child-Pugh B) and 3.1-fold in subjects with severe hepatic impairment (Child-Pugh C). No clinically significant differences in the pharmacokinetics of imlunestrant were observed in subjects with mild hepatic impairment (Child-Pugh A).
Drug Interaction Studies
Clinical Studies
Strong CYP3A Inhibitors: Imlunestrant AUC increased 2.1-fold and Cmax increased 1.9-fold following concomitant use of itraconazole (strong CYP3A inhibitor) for multiple days.
Strong CYP3A Inducers: Imlunestrant AUC decreased by 42% and Cmax decreased by 29% following concomitant use of carbamazepine (strong CYP3A inducer) for multiple days.
P-gp Substrates: Digoxin (P-gp substrate) AUC increased 1.4-fold and Cmax increased 1.6-fold following concomitant use of imlunestrant.
BCRP Substrates: Rosuvastatin (BCRP substrate) AUC increased 1.5-fold and Cmax increased 1.6-fold following concomitant use with imlunestrant.
Other Drugs: No clinically significant differences in the pharmacokinetics of imlunestrant were observed when used concomitantly with omeprazole (gastric acid-reducing agent) or quinidine (P-gp inhibitor).
No clinically significant differences in the pharmacokinetics of midazolam (CYP3A substrate), repaglinide (CYP2C8 substrate), omeprazole (CYP2C19 substrate), or dextromethorphan (CYP2D6 substrate) were observed when used concomitantly with imlunestrant.
In Vitro Studies
CYP Enzymes: Imlunestrant is an inhibitor of CYP2B6 and CYP2C9 but is not an inhibitor of CYP1A2. Imlunestrant is not an inducer of CYP1A2, CYP2B6, or CYP2C9.
Transporter Systems: Imlunestrant is not a substrate of BCRP, OCT1, OATP1B1, or OATP1B3.
Carcinogenesis
Carcinogenicity studies have not been conducted with imlunestrant.
Mutagenesis
Imlunestrant was not mutagenic in the bacterial reverse mutation (Ames) assay. Imlunestrant was clastogenic in an in vitro human lymphocyte micronucleus assay. Imlunestrant was not genotoxic in an in vivo rat bone marrow micronucleus test and did not induce DNA breaks in the liver and duodenum comet assays.
Impairment of Fertility
Fertility studies with imlunestrant in animals have not been conducted. In repeat-dose toxicity studies up to 6 months in rats and 3 months in cynomolgus monkeys, oral administration of imlunestrant resulted in follicular cysts in the ovary and atrophy in the vagina, cervix, and uterus at doses ≥ 10 mg/kg/day in rats (≥ 4 times the human AUC at the recommended dose) and ≥ 15 mg/kg/day in cynomolgus monkeys (≥1 times the human AUC at the recommended dose). Decreased sperm and cellular debris in the epididymis and spermatid retention in the testis were observed in male rats at ≥10 mg/kg/day. The effects of imlunestrant on male and female reproductive organs were reversible in rats following a 3-month recovery period. Reversibility was not assessed in cynomolgus monkeys.
In a 6-month repeat-dose toxicity study, oral administration of imlunestrant to rats resulted in epithelial hyperplasia in the urinary bladder, granulosa cell hyperplasia in the ovary, and hyperplasia in the mammary gland at doses ≥ 10 mg/kg/day (≥ 4 times the human AUC at the recommended dose). These effects, except urinary bladder effects, were reversible after a 3-month recovery period.
ER+, HER2-, ESR1-mutated Locally Advanced or Metastatic Breast Cancer
The efficacy of INLURIYO was evaluated in EMBER-3 (NCT04975308), a randomized, open-label, active-controlled, multicenter trial that enrolled 874 adult patients with ER+, HER2- locally advanced or metastatic breast cancer of which 323 patients had ESR1 mutations (ESR1m), who were previously treated with an aromatase inhibitor either alone or in combination with a CDK4/6 inhibitor. Patients were excluded if they were eligible to receive a PARP inhibitor. Patients were required to have progressed:
Patients were randomized 1:1:1 to
Randomization was stratified by previous treatment with CDK4/6 inhibitor (yes vs no), presence of visceral metastasis (yes vs no), and region (East Asia vs North America/Western Europe vs Others). ESR1m status was determined by blood circulating tumor deoxyribonucleic acid (ctDNA) analysis using the Guardant360 CDx assay and was limited to specific ESR1 mutations in the ligand binding domain. Patients were treated until disease progression or unacceptable toxicity.
INLURIYO as Monotherapy
The major efficacy outcomes for INLURIYO monotherapy were investigator-assessed progression-free survival (PFS) according to RECIST v1.1 in the overall population and in the population of patients whose tumors had an ESR1m. Other efficacy measures included overall survival (OS), blinded independent review committee (BIRC)-assessed PFS, and objective response rate (ORR). A statistically significant difference in PFS in the overall population was not observed; however, there was a statistically significant difference in PFS in the ESR1m population for INLURIYO monotherapy compared to investigator's choice of endocrine therapy (fulvestrant or exemestane) indicating the PFS benefit of INLURIYO monotherapy was limited to the ESR1m population.
Among the patients on the INLURIYO arm or investigator's choice of endocrine therapy who were positive for ESR1m (N=256), the median age was 61 years (range: 28-85 years); all patients were female, of which 11% were pre/perimenopausal; 61% were White, 26% Asian, 4% Black, 4% were American Indian or Alaskan Native, 4.7% missing, 0.8% multiple, 19% were Hispanic/Latino; and baseline ECOG performance status was 0 (63%) or 1 (37%). Most patients had visceral metastasis (59%) at baseline. Of the patients enrolled, 21% had received no endocrine therapy and 79% had received one line of endocrine therapy in the advanced or metastatic setting. Overall, 70% of patients were treated with a prior CDK4/6 inhibitor, 2.3% treated in the adjuvant setting and 67% treated in the advanced or metastatic setting.
Efficacy results for the ESR1m population are summarized in Table 7 and Figure 1. PFS assessment in the ESR1m population based on a BIRC was consistent with the investigator assessment. At the time of PFS analysis, overall survival data was immature with 31% of deaths in the ESR1m population.
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| INLURIYO N=138 | Fulvestrant or Exemestane N=118 | |
| Progression-free Survival (PFS)a, b | ||
| Number of PFS Events, n (%) | 109 (79) | 102 (86) |
| Median in months (95% CI) | 5.5 (3.9, 7.4) | 3.8 (3.7, 5.5) |
| Hazard Ratio (95% CI)c | 0.62 (0.46, 0.82) | |
| p-valued | 0.0008 | |
| Objective Response Rateb | ||
| Patients with Measurable Disease | 112 | 91 |
| ORR (95% CI) | 14% (8, 21) | 8% (2, 13) |
| Complete response rate | 0.9% | 0 |
| Partial response rate | 13% | 8% |
Figure 1: Kaplan-Meier Plot of Investigator-Assessed PFS for Patients with ESR1m, Treated with INLURIYO Monotherapy or Fulvestrant/Exemestane in EMBER-3
INLURIYO in Combination with Abemaciclib
The major efficacy outcome for INLURIYO in combination with abemaciclib was investigator-assessed PFS according to RECIST v1.1 in the overall population. Other efficacy measures included OS, BIRC-assessed PFS, and ORR. While the comparison of PFS between INLURIYO in combination with abemaciclib and INLURIYO monotherapy in the overall population was statistically significant, a PFS improvement was not demonstrated for INLURIYO monotherapy compared to investigator's choice of endocrine therapy in either the overall or ESR1m not detected populations, indicating that the benefit for INLURIYO monotherapy was only observed in the ESR1m population. Therefore, exploratory analyses of PFS, OS and ORR in the ESR1m population comparing INLURIYO in combination with abemaciclib and INLURIYO monotherapy were performed.
Among the patients on the INLURIYO in combination with abemaciclib arm or the INLURIYO monotherapy arm who were positive for ESR1m (n=159), the median age was 62 years (range: 31-85 years); all patients were female, of which 12% were pre/perimenopausal; 60% were White, 27% Asian, 5% Black, 0.6% were American Indian or Alaskan Native, 0.6% multiple races, 7% missing, 12% were Hispanic/Latino, 75% not Hispanic/Latino, 13% not reported/missing; and all patients had a baseline ECOG performance status of 0 (66%) or 1 (34%). Most patients had visceral metastasis (58%) at baseline. Of the patients enrolled, all received a prior line of endocrine therapy and 81% had received one line of endocrine therapy in the advanced or metastatic setting. Overall, 79% of patients were treated with a prior CDK4/6 inhibitor, 4.4% were treated in the adjuvant setting and 74% were treated in the advanced or metastatic setting. Among the patients who had received prior CDK4/6 inhibitors, the specific CDK4/6 inhibitor received was palbociclib 65%, ribociclib 28%, and abemaciclib 6%.
The exploratory analyses results in the ESR1m population are summarized in Table 8 and Figure 2. PFS assessment in the ESR1m population based on a BIRC was consistent with the investigator assessment. At the time of interim analysis, overall survival data was immature with 35% of deaths in the ESR1m population.
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| INLURIYO + Abemaciclib N=67 | INLURIYO N=92 | |
| Progression-free Survival (PFS)a,b | ||
| Number of PFS Events, n (%) | 36 (54) | 71 (77) |
| Median in months (95% CI) | 11.1 (7.4, 13.7) | 5.5 (3.8, 7.2) |
| Hazard Ratio (95% CI)c | 0.53 (0.35, 0.80) | |
| Objective Response Rate a, b | ||
| Patients with Measurable Disease | 54 | 74 |
| ORR (95% CI) | 35% (22, 48) | 15% (7, 23) |
| Complete response rate | 1.9% | 1.4% |
| Partial response rate | 33% | 14% |
Figure 2: Kaplan-Meier Plot of Investigator-Assessed PFS for Patients with ESR1m, Treated with INLURIYO in Combination with Abemaciclib or INLURIYO Monotherapy in EMBER-3
How Supplied
INLURIYO 200 mg tablets are white, film coated, capsule-shaped tablets with “LILLY” on one side and “1717” and an elongated 4-point starburst on the other side.
INLURIYO 200 mg tablets are supplied in either a 28-count or 56-count bottle configuration.
Storage and Handling
Store at 20°C to 25°C (68°F to 77°F). Excursions between 15°C to 30°C (59°F to 86°F) are permitted [see USP Controlled Room Temperature].
Disposal
Dispose unused medication via a take-back option if available. Otherwise, follow FDA instructions for disposing medication in the household trash, www.fda.gov/drugdisposal. Do NOT flush down the toilet.
Advise patients to read the FDA-approved patient labeling (Patient Information).
Dyslipidemia
Advise patients that hypercholesterolemia and hypertriglyceridemia may occur while taking INLURIYO. Inform patients that lipid profile monitoring will be performed prior to starting and periodically while taking INLURIYO [see Adverse Reactions (6.1)].
Embryo-Fetal Toxicity
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].
Advise females of reproductive potential to use effective contraception during treatment with INLURIYO and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with INLURIYO and for 1 week after the last dose [see Use in Specific Populations (8.3)].
Refer to the Prescribing Information of abemaciclib when administered in combination with INLURIYO for pregnancy and contraception information. When used in combination, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of the individual products.
Lactation
Advise women not to breastfeed during treatment with INLURIYO and for 1 week after the last dose [see Use in Specific Populations (8.2)].
Refer to the Prescribing Information of abemaciclib when administered in combination with INLURIYO for lactation information. When used in combination, advise patients to not breastfeed during treatment and for the longest post-treatment duration recommended in the Prescribing Information of the individual products.
Infertility
Advise males and females of reproductive potential that INLURIYO may impair fertility [see Use in Specific Populations (8.3)].
Dosing Instructions
Instruct patients to take INLURIYO at approximately the same time each day and to swallow the tablet(s) whole. Tablets should not be chewed, crushed, or split prior to swallowing [see Dosage and Administration (2.2)].
Advise patients to take INLURIYO without food, either 2 hours before food or 1 hour after food [see Dosage and Administration (2.2)].
Instruct patient that if a dose of INLURIYO is missed by more than 6 hours or vomiting occurs, skip the dose and take the next dose the following day at its regularly scheduled time [see Dosage and Administration (2.2)].
Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA
Copyright © 2025, 2026, Eli Lilly and Company. All rights reserved.
Pat.: www.lilly.com/patents
INL-0003-USPI-20260918
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| PATIENT INFORMATION INLURIYO® (en-loo-ree-yoh) imlunestrant tablets | ||
| What is INLURIYO? INLURIYO is a prescription medicine that is used alone or in combination with the medicine abemaciclib to treat adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 (ESR1)-mutated advanced breast cancer or breast cancer that has spread to other parts of the body (metastatic), and whose disease has progressed after at least 1 line of endocrine therapy. Your healthcare provider will perform a test to make sure that INLURIYO is right for you. When INLURIYO is used in combination with abemaciclib, read the Patient Information for abemaciclib. It is not known if INLURIYO is safe and effective in children. | ||
Before taking INLURIYO, tell your healthcare provider about all of your medical conditions including if you:
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Females who are able to become pregnant:
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Males with female partners who are able to become pregnant:
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| Tell your healthcare provider about all of the medicines you take, including prescription and over-the counter medicines, vitamins, and herbal supplements. INLURIYO and other medicines may affect each other causing side effects. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine. | ||
How should I take INLURIYO?
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| What are the possible side effects of INLURIYO? The most common side effects of INLURIYO when taken alone include: | ||
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| The most common side effects of INLURIYO when taken with abemaciclib include: | ||
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| Your healthcare provider may change your dose, temporarily stop, or completely stop treatment with INLURIYO if you develop certain side effects. INLURIYO may affect fertility in males and in females who are able to become pregnant. Talk to your healthcare provider if this is a concern for you. These are not all of the possible side effects of INLURIYO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. | ||
How should I store INLURIYO?
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| Keep INLURIYO and all medicines out of the reach of children. | ||
| General information about the safe and effective use of INLURIYO. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use INLURIYO for a condition for which it was not prescribed. Do not give INLURIYO to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for more information about INLURIYO. | ||
| What are the ingredients in INLURIYO? Active ingredient: imlunestrant Inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and microcrystalline cellulose. The tablet coating contains polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. INLURIYO is a trademark of Eli Lilly and Company. All rights reserved. Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA Copyright © 2025, 2026, Eli Lilly and Company. All rights reserved. For more information, go to www.INLURIYO.com or call 1-800-545-5979
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INL-0003-PPI-20260918
NDC 0002-1717-56
Rx only
InluriyoTM
(imlunestrant) tablets
200 mg
56 tablets
Lilly
| Resource | Code type | Value | Equivalent identifiers | Source image |
|---|---|---|---|---|
| Barcode | DataBar Limited | (01)00300021717568 | GTIN-14: 00300021717568 GTIN-12: 300021717568 UPC-A: 300021717568 EAN-13: 0300021717568 GTIN storage (14 digits): 00300021717568 | inluriyo-200mg-label-56ct-2397.jpg |
| Product concept | Relation | Version | Effective |
|---|---|---|---|
| 362d7abb-94e6-4c60-9a58-266894157713 | Product name | 1 | 20231023 |
| 816b97af-edc5-4060-aff1-b814bdbcad50 | Product name | 1 | 20190415 |
| 419aab54-5d5a-4146-9453-026d4a9991be | Product name | 2 | 20170525 |
| 89dac932-b90a-4410-9ab1-84c53e57de25 | Product name | 1 | 20150316 |
| d723478e-ad4a-ec23-6bd7-cfe33e1e3840 | Product name | 1 | 20140508 |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 0002-1717-28 | EA - Each | 0002-1717 | ac6b3ee9-2937-461f-a2f7-39ec4e74e599 | 1 | 2025-10-14 |
| 0002-1717-56 | EA - Each | 0002-1717 | f875f7b0-d5ca-4b4b-ab64-eb578468b990 | 1 | 2025-10-14 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 0002-1717 | 0002-1717-28, 0002-1717-56, 0002-1717-61 |
Every source-derived ingredient row is available through these pages.
| Name | UNII | Kind |
|---|---|---|
| imlunestrant | 9CXQ3PF69U | ACTIB |
| Croscarmellose Sodium | M28OL1HH48 | IACT |
| Hydroxypropyl Cellulose, Unspecified | 9XZ8H6N6OH | IACT |
| Magnesium Stearate | 70097M6I30 | IACT |
| Microcrystalline Cellulose | OP1R32D61U | IACT |
| Polyethylene Glycol 3350 | G2M7P15E5P | IACT |
| Polyvinyl Alcohol, Unspecified | 532B59J990 | IACT |
| Talc | 7SEV7J4R1U | IACT |
| Titanium Dioxide | 15FIX9V2JP | IACT |
| Version | Effective date | Source | Hydrated |
|---|---|---|---|
| 7 | 2026-06-04 | daily-update | 2026-06-11 05:11:58 |
| 6 | 2025-11-20 | full-release | 2026-05-31 22:07:03 |
| 4 | 2025-09-25 | monthly-update | 2026-06-03 17:41:46 |
All distinct exact application/product contexts derived from this label’s complete NDC list are paginated below.
| Application-product | Trade name | Ingredient | Strength | Dosage form / route | TE codes | RLD / RS | Approval date |
|---|---|---|---|---|---|---|---|
| N218881-001 | INLURIYO | IMLUNESTRANT TOSYLATE | EQ 200MG BASE | TABLET / ORAL | RLD, RS | 2025-09-25 |
| Application-product | Patent | Expiration | Use code | Coverage / status | Submission date |
|---|---|---|---|---|---|
| N218881-001 | 10654866 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 |
| N218881-001 | 11117902 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 |
| Application-product | Exclusivity code | Expiration |
|---|---|---|
| N218881-001 | NCE | 2030-09-25 |
Observed FDA ZIP history: Each table is queried independently by exact application/product key from successfully parsed Orange Book snapshots. Capture times identify archived source observations; absence or a change between snapshots is not inferred. FDA publication files that were not recoverable as structured ZIP data are not represented as states.
| Captured | Edition | Application-product | Trade name | Strength | Dosage form / route | Product TE source text | RLD / RS | Approval date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | N218881-001 | INLURIYO | EQ 200MG BASE | TABLET / ORAL | RLD, RS | 2025-09-25 | 84e616aacf4f… | |
| 2026-08-18 06:07:40 | 2026-07 | N218881-001 | INLURIYO | EQ 200MG BASE | TABLET / ORAL | RLD, RS | 2025-09-25 | caaa826d4ba7… | |
| 2026-02-19 14:30 UTC | 2026-02 | N218881-001 | INLURIYO | EQ 200MG BASE | TABLET / ORAL | RLD, RS | 2025-09-25 | 011fe1cb6892… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N218881-001 | INLURIYO | EQ 200MG BASE | TABLET / ORAL | RLD, RS | 2025-09-25 | 31067a03dcf5… | |
| 2026-07-26 02:55 UTC · 3 captures of this ZIP | 2026-06 | N218881-001 | INLURIYO | EQ 200MG BASE | TABLET / ORAL | RLD, RS | 2025-09-25 | a50c72e98297… |
| Captured | Edition | Application-product | Patent | Expiration | Use code | Coverage / status | Submission date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | N218881-001 | 10654866 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N218881-001 | 11117902 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 | 84e616aacf4f… |
| 2026-08-18 06:07:40 | 2026-07 | N218881-001 | 10654866 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N218881-001 | 11117902 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 | caaa826d4ba7… |
| 2026-02-19 14:30 UTC | 2026-02 | N218881-001 | 10654866 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N218881-001 | 11117902 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 | 011fe1cb6892… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N218881-001 | 10654866 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N218881-001 | 11117902 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 | 31067a03dcf5… |
| 2026-07-26 02:55 UTC · 3 captures of this ZIP | 2026-06 | N218881-001 | 10654866 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 | a50c72e98297… |
| 2026-07-26 02:55 UTC · 3 captures of this ZIP | 2026-06 | N218881-001 | 11117902 | 2039-07-11 | U-4278 | Drug substance, Drug product | 2025-10-16 | a50c72e98297… |
| Captured | Edition | Application-product | Exclusivity code | Expiration | Source SHA-256 |
|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | N218881-001 | NCE | 2030-09-25 | 84e616aacf4f… |
| 2026-08-18 06:07:40 | 2026-07 | N218881-001 | NCE | 2030-09-25 | caaa826d4ba7… |
| 2026-02-19 14:30 UTC | 2026-02 | N218881-001 | NCE | 2030-09-25 | 011fe1cb6892… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N218881-001 | NCE | 2030-09-25 | 31067a03dcf5… |
| 2026-07-26 02:55 UTC · 3 captures of this ZIP | 2026-06 | N218881-001 | NCE | 2030-09-25 | a50c72e98297… |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| Inluriyo | IMLUNESTRANT | Eli Lilly and Company | 5bc172e4-e8a2-441a-be52-279a7f890196 | 2026-06-04 | Warnings, Adverse reactions | 0002-1717-56 0002-1717-28 0002-1717-61 0002-1717 00002171728 00002171761 00002171756 5bc172e4-e8a2-441a-be52-279a7f890196 |
Adverse event summaries are temporarily unavailable. Other product information remains available.