imlunestrant 200 MG Oral Tablet [Inluriyo]

INDICATIONS AND USAGE 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. INLURIYO TM is an estrogen receptor antagonist indicated for: treatment of adults with ER-positive, HER2-negative, ESR1 -mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy ( 1 )

DOSAGE AND ADMINISTRATION 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 ) 2.1 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 [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 . 2.2 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 [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. 2.3 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) 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 Suspend until toxicity resolves to baseline or ≤Grade 1. Resume INLURIYO at the same dose level. Grade 3 or 4 (except non-hepatic asymptomatic laboratory changes) Suspend until toxicity resolves to baseline or ≤Grade 1. Resume INLURIYO at next lower dose level. Table 2: INLURIYO Dosage Modification - Hepatotoxicity Abbreviation: ALT = alanine aminotransferase, AST = aspartate aminotransferase, TBL=total bilirubin, ULN = upper limit of normal. Monitor alanine aminotransferase (ALT)/aspartate aminotransferase (AST) during imlunestrant therapy as clinically indicated. Liver Transaminase INLURIYO Dosage Modifications Persistent or Recurrent: AST/ALT >3.0-5.0×ULN Suspend until toxicity resolves to baseline or to >ULN-3.0×ULN. Resume INLURIYO at the same dose level. 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) Suspend until toxicity resolves to baseline or to >ULN-3.0×ULN. Resume INLURIYO at next lower dose level 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 Discontinue INLURIYO. 2.4 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 [see Clinical Pharmacology ( 12.3 )] . 2.5 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 [see Drug Interactions ( 7.1 )] . 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 )] .

WARNINGS AND PRECAUTIONS 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 ) 5.1 Embryo-Fetal Toxicity 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 )] .

CONTRAINDICATIONS None. None. ( 4 )

Mechanism of Action 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.