These Highlights Do Not Include All The Information Needed To Use Inluriyo Safely And Effectively. See Full Prescribing Information For Inluriyo.

How Supplied

INLURIYO 200 mg tablets are white 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

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)].

INL-0001-PPI-202509

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.

INLURIYO tablets contain imlunestrant, an estrogen receptor antagonist. The chemical name for imlunestrant tosylate is (5R)-5-(4-(2-(3-(flouromethyl)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 are tablets 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.

The safety and effectiveness of INLURIYO have not been established in pediatric patients.

Of 327 patients who received INLURIYO 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 have been observed between patients 65 years of age and older and younger adult patients.

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, 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:

• Within 12 months of completing neoadjuvant or adjuvant aromatase inhibitor therapy with no systemic treatment for recurrent disease or
• Greater than 12 months after neoadjuvant or adjuvant endocrine therapy or de novo metastatic disease and had progressed on only one line of aromatase inhibitor therapy.

Patients were randomized 1:1:1 to INLURIYO 400 mg orally once daily; or investigator's choice of endocrine therapy [fulvestrant 500 mg IM on days 1, 15, 29, and once monthly thereafter (n=111) or exemestane 25 mg orally once daily (n=6)]; or an additional investigational combination regimen. 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.

The major efficacy outcome was investigator assessed progression-free survival (PFS) according to RECIST v1.1. Other efficacy measures included overall survival (OS), blinded independent review committee (BIRC)-assessed PFS, and objective response rate (ORR).

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 CDK4/6i, 2.3% treated in the adjuvant setting and 67% treated in the advanced or metastatic setting.

The efficacy results from these patients are summarized in Table 5 and Figure 1. There was a statistically significant difference in investigator-assessed PFS in the ESR1m population for INLURIYO compared to investigator's choice of endocrine therapy (fulvestrant or exemestane). PFS assessment 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.

Figure 1: Kaplan-Meier Plot of Investigator-Assessed PFS for Patients with ESR1 m, Treated with INLURIYO or Fulvestrant/Exemestane in EMBER-3

None.

The most common (incidence ≥10%) adverse reactions, including laboratory abnormalities were: hemoglobin decreased, musculoskeletal pain, calcium decreased, neutrophils decreased, AST increased, fatigue, diarrhea, ALT increased, triglycerides increased, nausea, platelets decreased, constipation, cholesterol increased, and abdominal pain. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Strong CYP3A Inhibitors: Avoid concomitant use with INLURIYO. If concomitant use cannot be avoided, decrease the INLURIYO dosage. (2.5, 7.1)
• Strong CYP3A Inducers: Avoid concomitant use with INLURIYO. If concomitant use cannot be avoided, increase the INLURIYO dosage (2.5, 7.1).

Imlunestrant exposure-response relationships and the time course of pharmacodynamics have not been fully characterized.

Imlunestrant pharmacokinetics were observed at steady state at the approved recommended dosage and are presented as mean (%CV) unless otherwise specified. The maximum concentration (C_max) of imlunestrant is 141 ng/mL (45%) and the area under the concentration-time curve (AUC) is 2,400 ng*h/mL (46%). Imlunestrant C_max 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.

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-approved test [see Indications and Usage (1) and Clinical Studies (14.1)].

Information on FDA-approved tests for the detection of ESR1 mutations in breast cancer is available at: https://www.fda.gov/CompanionDiagnostics.

Reduce the dose of INLURIYO in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dosage modification is recommended for patients with mild hepatic impairment (Child-Pugh A) [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].

INLURIYO is indicated 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 with disease progression following at least one line of endocrine therapy.

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.

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)].

• Embryo-Fetal Toxicity: INLURIYO can cause fetal harm. Advise of the potential risk to a fetus and to use effective contraception. (5.1, 8.1, 8.3)

• Select patients for treatment based on the presence of ESR1 mutations. (2.1)
• The recommended dosage is 400 mg orally once daily, on an empty stomach. (2.2)
• Reduce the dose in patients with moderate or severe hepatic impairment (2.4, 8.6)
• Dosage modifications may be required. (2.3, 2.4, 2.5)

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.

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.

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 (14.1)]. 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 (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 and COVID-19 (each 0.9%); and increased alanine aminotransferase, 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 aspartate aminotransferase (0.6%); and increased alanine aminotransferase, anemia, fatigue, interstitial lung disease, nausea, neutropenia, and vomiting (each 0.3%).

The most common (≥10%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased, musculoskeletal pain, calcium decreased, neutrophils decreased, AST increased, fatigue, diarrhea, ALT increased, triglycerides increased, nausea, platelets decreased, constipation, cholesterol increased, and abdominal pain.

Table 3 summarizes the adverse reactions in EMBER-3.

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.

• Lactation: Advise not to breastfeed. (8.2)

Advise patients to read the FDA-approved patient labeling (Patient Information).

The recommended dosage of INLURIYO 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.

Pre/perimenopausal women and men should receive a gonadotropin-releasing hormone agonist (GnRH) according to current clinical practice standards.

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.

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.

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.

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)].

INLURIYO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

NDC 0002-1717-56

Rx only

Inluriyo^TM

(imlunestrant) tablets

200 mg

56 tablets

Lilly

How Supplied

INLURIYO 200 mg tablets are white 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

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)].

INL-0001-PPI-202509

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.

INLURIYO tablets contain imlunestrant, an estrogen receptor antagonist. The chemical name for imlunestrant tosylate is (5R)-5-(4-(2-(3-(flouromethyl)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 are tablets 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.

The safety and effectiveness of INLURIYO have not been established in pediatric patients.

Of 327 patients who received INLURIYO 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 have been observed between patients 65 years of age and older and younger adult patients.

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, 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:

• Within 12 months of completing neoadjuvant or adjuvant aromatase inhibitor therapy with no systemic treatment for recurrent disease or
• Greater than 12 months after neoadjuvant or adjuvant endocrine therapy or de novo metastatic disease and had progressed on only one line of aromatase inhibitor therapy.

Patients were randomized 1:1:1 to INLURIYO 400 mg orally once daily; or investigator's choice of endocrine therapy [fulvestrant 500 mg IM on days 1, 15, 29, and once monthly thereafter (n=111) or exemestane 25 mg orally once daily (n=6)]; or an additional investigational combination regimen. 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.

The major efficacy outcome was investigator assessed progression-free survival (PFS) according to RECIST v1.1. Other efficacy measures included overall survival (OS), blinded independent review committee (BIRC)-assessed PFS, and objective response rate (ORR).

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 CDK4/6i, 2.3% treated in the adjuvant setting and 67% treated in the advanced or metastatic setting.

The efficacy results from these patients are summarized in Table 5 and Figure 1. There was a statistically significant difference in investigator-assessed PFS in the ESR1m population for INLURIYO compared to investigator's choice of endocrine therapy (fulvestrant or exemestane). PFS assessment 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.

Figure 1: Kaplan-Meier Plot of Investigator-Assessed PFS for Patients with ESR1 m, Treated with INLURIYO or Fulvestrant/Exemestane in EMBER-3

None.

The most common (incidence ≥10%) adverse reactions, including laboratory abnormalities were: hemoglobin decreased, musculoskeletal pain, calcium decreased, neutrophils decreased, AST increased, fatigue, diarrhea, ALT increased, triglycerides increased, nausea, platelets decreased, constipation, cholesterol increased, and abdominal pain. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Strong CYP3A Inhibitors: Avoid concomitant use with INLURIYO. If concomitant use cannot be avoided, decrease the INLURIYO dosage. (2.5, 7.1)
• Strong CYP3A Inducers: Avoid concomitant use with INLURIYO. If concomitant use cannot be avoided, increase the INLURIYO dosage (2.5, 7.1).

Imlunestrant exposure-response relationships and the time course of pharmacodynamics have not been fully characterized.

Imlunestrant pharmacokinetics were observed at steady state at the approved recommended dosage and are presented as mean (%CV) unless otherwise specified. The maximum concentration (C_max) of imlunestrant is 141 ng/mL (45%) and the area under the concentration-time curve (AUC) is 2,400 ng*h/mL (46%). Imlunestrant C_max 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.

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-approved test [see Indications and Usage (1) and Clinical Studies (14.1)].

Information on FDA-approved tests for the detection of ESR1 mutations in breast cancer is available at: https://www.fda.gov/CompanionDiagnostics.

Reduce the dose of INLURIYO in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dosage modification is recommended for patients with mild hepatic impairment (Child-Pugh A) [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].

INLURIYO is indicated 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 with disease progression following at least one line of endocrine therapy.

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.

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)].

• Embryo-Fetal Toxicity: INLURIYO can cause fetal harm. Advise of the potential risk to a fetus and to use effective contraception. (5.1, 8.1, 8.3)

• Select patients for treatment based on the presence of ESR1 mutations. (2.1)
• The recommended dosage is 400 mg orally once daily, on an empty stomach. (2.2)
• Reduce the dose in patients with moderate or severe hepatic impairment (2.4, 8.6)
• Dosage modifications may be required. (2.3, 2.4, 2.5)

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.

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.

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 (14.1)]. 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 (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 and COVID-19 (each 0.9%); and increased alanine aminotransferase, 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 aspartate aminotransferase (0.6%); and increased alanine aminotransferase, anemia, fatigue, interstitial lung disease, nausea, neutropenia, and vomiting (each 0.3%).

The most common (≥10%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased, musculoskeletal pain, calcium decreased, neutrophils decreased, AST increased, fatigue, diarrhea, ALT increased, triglycerides increased, nausea, platelets decreased, constipation, cholesterol increased, and abdominal pain.

Table 3 summarizes the adverse reactions in EMBER-3.

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.

• Lactation: Advise not to breastfeed. (8.2)

Advise patients to read the FDA-approved patient labeling (Patient Information).

The recommended dosage of INLURIYO 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.

Pre/perimenopausal women and men should receive a gonadotropin-releasing hormone agonist (GnRH) according to current clinical practice standards.

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.

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.

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.

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)].

INLURIYO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

NDC 0002-1717-56

Rx only

Inluriyo^TM

(imlunestrant) tablets

200 mg

56 tablets

Lilly