Inluriyo Drug Information

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.

Patient Selection

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

Recommended Dosage and Administration

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. 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.

Dosage Modifications for Adverse Reactions

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.

Table 1: INLURIYO Dosage Modification - Adverse Reactions (except hepatotoxicity) Table 2: INLURIYO Dosage Modification - Hepatotoxicity

Dosage in Patients with Hepatic Impairment

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.

Dosage Modifications for Drug Interactions 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. 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.

Clinical Trial Experience

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. 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. 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. Table 4 summarizes the laboratory abnormalities in EMBER-3.

Table 4: Select Laboratory Abnormalities (≥10%) That Worsened from Baseline in Patients Who Received INLURIYO in EMBER-3 0

Effects of Other Drugs on INLURIYO Strong CYP3A Inhibitors

Avoid concomitant use of INLURIYO with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce the dosage of INLURIYO. Imlunestrant is a CYP3A substrate.

Concomitant use of a strong CYP3A inhibitor increases imlunestrant exposure, which may increase the risk of INLURIYO-associated adverse reactions. Strong CYP3A Inducers Avoid concomitant use of INLURIYO with strong CYP3A inducers. Concomitant use of a strong CYP3A inducer decreases imlunestrant exposure, which may reduce effectiveness of INLURIYO.

Effects of INLURIYO on Other Drugs 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.

Pregnancy Risk Summary Based on findings in animals and its mechanism of action, INLURIYO can cause fetal harm when administered to a pregnant woman. 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. 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.

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