Jideytro Tablet, Film Coated
FDA Label NDC 85001-102

JIDEYTRO is indicated for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who received a prior ROS1 kinase inhibitor [see Dosage and Administration (2.1), Clinical Studies (14.1)].

Before initiating JIDEYTRO, evaluate creatine phosphokinase (CPK) level, electrocardiogram (ECG), electrolytes, lipase and amylase [see Warnings and Precautions (5.2, 5.5, 5.6)].

The recommended dosage of JIDEYTRO is 100 mg taken orally once daily, with or without food, until disease progression or unacceptable toxicity [see Clinical Pharmacology (12.3)].

Swallow JIDEYTRO tablets whole. Do not split, chew, crush, or dissolve the tablet prior to swallowing.

Missed Dose

If a dose of JIDEYTRO is missed within 12 hours of the regularly scheduled dose, administer the missed dose as soon as possible. If a dose is missed by 12 hours or more, take the next dose at its scheduled time.

Vomiting

If vomiting occurs at any time after taking JIDEYTRO, take the next dose at its scheduled time.

The recommended dosage reductions of JIDEYTRO for the management of adverse reactions are provided in Table 1.

The recommended dosage modifications of JIDEYTRO for the management of adverse reactions are provided in Table 2.

Tablets: 25 mg: pink, oblong, film-coated, debossed with "25" on one side and "ZDS" on the other side.

Tablets: 100 mg: yellow, oblong, film-coated, debossed with "100" on one side and "ZDS" on the other side.

None.

JIDEYTRO can cause central nervous system adverse reactions.

In the pooled safety population [see Adverse Reactions (6.1)], a broad spectrum of central nervous system (CNS) adverse reactions, including dizziness, ataxia, cognitive and psychiatric disorders, occurred in 25% of patients who received JIDEYTRO; of these, 2.5% were Grade 3 or 4. One patient (0.2%) with brain metastases experienced a Grade 3 seizure.

Dizziness, including vertigo, presyncope and positional dizziness occurred in 12% of patients who received JIDEYTRO; of these 0.2% were Grade 3. The median time to onset of dizziness was 22 days (range: 1 day to 9 months). Dosage interruption of JIDEYTRO for dizziness was required in 0.4% of patients, and 0.7% of patients required dose reduction.

Ataxia, including gait disturbance and balance disorder, occurred in 2% of patients who received JIDEYTRO and were all Grade 1 or 2. The median time to onset of ataxia was 64 days (range: 6 days to 2.5 years).

Cognitive impairment occurred in 9% of patients who received JIDEYTRO, of these 1.6% were Grade 3 or 4. Cognitive impairment included memory impairment (3.1%), cognitive disorder (1.6%), hallucination (1.1%), delirium (1.1%), aphasia (0.9%), amnesia (0.7%), confusional state (0.7%), anterograde amnesia (0.2%), disturbance in attention (0.4%), slow speech (0.2%). The median time to onset of cognitive impairment was 43 days (range: 4 days to 1.9 years). Dose interruption of JIDEYTRO for cognitive impairment was required in 1.3% of patients.

Psychiatric disorders occurred in 6% of patients who received JIDEYTRO, of these 0.7% were Grade 3 or 4. Psychiatric disorders included anxiety (3.1%), depression (1.3%), agitation (0.7%), affect lability (0.4%), irritability (0.4%), abnormal behavior (0.2%), depressed mood (0.2%), personality change (0.2%), psychotic disorder (0.2%), and suicidal ideation (0.2%). The median time to onset of psychiatric disorders was 57 days (range: 1 day to 10 months). Dosage interruption of JIDEYTRO for psychiatric disorders was required in 0.9% of patients. Advise patients and caregivers of the risk of CNS adverse reactions with JIDEYTRO. Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination such as operating machinery or driving a motor vehicle if they are experiencing CNS reactions. Monitor patients for CNS adverse reactions and suicidal thoughts and behaviors during treatment with JIDEYTRO. Withhold and then resume at the same or reduced dose upon improvement or permanently discontinue JIDEYTRO based on severity [see Dosage and Administration (2.3)].

JIDEYTRO can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death. JIDEYTRO has not been studied in patients with a history of QTcF >450 msec on more than one assessment prior to initiation.

In the pooled safety population [see Adverse Reactions (6.1)], of the 435 patients who underwent at least one post baseline electrocardiogram (ECG) assessment, 2% experienced an increase in QTcF of >60 msec compared to baseline after receiving JIDEYTRO and 0.2% increase in QTcF to >500 msec. The median time from the first dose of JIDEYTRO to the onset of QTc prolongation was 15 days (range: 1 day to approximately 1 month). QTc prolongation led to dose interruption in 0.4% of patients who received JIDEYTRO.

Evaluate ECGs and electrolytes prior to administration of JIDEYTRO and monitor periodically during treatment. Adjust the frequency of monitoring based on risk factors such as known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, and concomitant medications associated with QTc interval prolongation. Withhold, then resume at the same or reduced dose, or permanently discontinue JIDEYTRO based on severity [see Dosage and Administration (2.3)].

JIDEYTRO can cause severe or life-threatening interstitial lung disease (ILD) or pneumonitis.

In the pooled safety population [see Adverse Reactions (6.1)], interstitial lung disease (ILD)/pneumonitis occurred in 1.8% of patients treated with JIDEYTRO, including Grade 3 or 4 in 0.4%. The median time to first onset of ILD/pneumonitis was 4.5 months (range: 8 days to 11 months).

ILD/pneumonitis led to dose interruption of JIDEYTRO in 0.7% of patients. ILD/pneumonitis required dose reduction in 0.2% of patients and permanent discontinuation of JIDEYTRO in 0.4% of patients.

Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Immediately withhold JIDEYTRO in patients with suspected ILD/pneumonitis, then upon recovery resume at the same or reduced dose or permanently discontinue based on severity [see Dosage and Administration (2.3)].

JIDEYTRO can increase the risk of skeletal fractures.

In the pooled safety population [see Adverse Reactions (6.1)], 5 patients (1.1%) experienced skeletal fractures, and Grade 3 ankle fractures occurred in two patients (0.4%) who received JIDEYTRO. Some fractures occurred in the setting of an accidental fall or other predisposing factors such as osteoporosis, bone metastasis, and age-related degenerative conditions. The median time to fracture was 48 days (range: 32 days to approximately 6 months). JIDEYTRO was interrupted in 0.4% of patients for fractures.

JIDEYTRO can cause myalgia with creatine phosphokinase (CPK) elevation.

In the pooled safety population [see Adverse Reactions (6.1)], myalgia occurred in 13% of patients who received JIDEYTRO. Based on laboratory values, concurrent myalgia with increased CPK occurred in 2.1% of patients. The median time to onset of myalgia for these patients with CPK elevation was 2 months (range: 8 days to 6 months). 

Advise patients to report unexplained muscle pain or tenderness. Monitor serum CPK levels prior to administration of JIDEYTRO and every 2 weeks during the first month of treatment and then every 1 to 2 months and as clinically indicated in patients reporting unexplained muscle pain or tenderness. Withhold, then resume at the same or reduced dose, or permanently discontinue JIDEYTRO based on severity [see Dosage and Administration (2.3)].

JIDEYTRO can cause pancreatic toxicity.

In the pooled safety population [see Adverse Reactions (6.1)], among the subgroup of patients who underwent pancreatic lab testing, increased amylase occurred in 22% and increased lipase occurred in 25% of patients treated with JIDEYTRO. Grade 3 increased lipase occurred in 8% of these patients. Grade 3 lipase elevation resulted in JIDEYTRO dose reduction in one patient. The median time-to-onset of Grade 3 increased lipase was 143 days (range: 28 to 249 days). In the pooled safety population [see Adverse Reactions (6.1)], Grade 3 pancreatitis occurred in one patient (0.2%) treated with JIDEYTRO.

Evaluate amylase and lipase prior to administration of JIDEYTRO and monitor periodically during treatment. Based on the severity of the adverse reaction, temporarily withhold, reduce the dose, or permanently discontinue JIDEYTRO [see Dosage and Administration (2.3)].

Based on literature reports in humans with congenital mutations leading to changes in tropomyosin receptor kinase (TRK) signaling, findings from animal studies and its mechanism of action, JIDEYTRO can cause fetal harm when administered to a pregnant woman.

In an animal reproduction study, oral administration of zidesamtinib to pregnant rats during the period of organogenesis resulted in embryo-fetal mortality, alterations to growth, and structural abnormalities at maternal exposures approximately equivalent to the human exposure at the recommended dose based on area under the curve (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 JIDEYTRO and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with JIDEYTRO and for 3 months after the last dose [see Use in Specific Populations (8.1, 8.3)].

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Central Nervous System Adverse Reactions [see Warnings and Precautions (5.1)]
• QTc Interval Prolongation [see Warnings and Precautions (5.2)]
• Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.3)]
• Skeletal Fractures [see Warnings and Precautions (5.4)]
• Myalgia with Creatine Phosphokinase Elevation [see Warnings and Precautions (5.5)]
• Pancreatic Toxicity [see Warnings and Precautions (5.6)]

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 pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to JIDEYTRO in 446 patients with ROS1-positive NSCLC (n=432) and other solid tumors (n=14) who received JIDEYTRO at a dose of 100 mg orally once daily until disease progression or unacceptable toxicity in ARROS-1 [see Clinical Studies (14.1)]. Among 446 patients who received JIDEYTRO, 44% were exposed for 6 months or longer and 14% were exposed for greater than one year.  In this pooled safety population, the most common (≥15%) adverse reactions included: edema (38%), peripheral neuropathy (25%), constipation (17%), fatigue (16%), dyspnea (15%). The most common Grade 3 or 4 laboratory abnormalities (≥2%), were increased lipase (8%), increased creatine phosphokinase (CPK) (4%), increased triglycerides (3.5%), decreased lymphocytes (2.7%), and decreased hemoglobin (2.3%).

Previously Treated ROS1-positive NSCLC

The safety of JIDEYTRO was evaluated in ARROS-1 [see Clinical Studies (14.1)]. Patients received JIDEYTRO 100 mg orally once daily until disease progression or unacceptable toxicity. Among the 432 patients who received JIDEYTRO, 44% were exposed to JIDEYTRO for 6 months or longer, and 15% were exposed for greater than 1 year. 

The median age of patients who received JIDEYTRO was 58 years (range: 26 to 87); 62% female; 41% White, 41% Asian, 3.7% Black or African American, 0.2% American Indian or Alaska Native, 14% other races, multiple races or race unknown, and 4.6% of patients were of Hispanic or Latino ethnicity.

Serious adverse reactions occurred in 22% of patients who received JIDEYTRO. Serious adverse reactions in ≥2% of patients included pneumonia (6%) and dyspnea (2.5%). Fatal adverse reactions occurred in 2.3% of patients who received JIDEYTRO, including pneumonia (0.5%), cerebrovascular accident (0.2%), COVID-19 (0.2%), dyspnea (0.2%), infectious pleural effusion (0.2%), influenza (0.2%), myocardial infarction (0.2%), myocarditis (0.2%), and respiratory failure (0.2%). 

Permanent discontinuation of JIDEYTRO due to an adverse reaction occurred in 2.3% of patients.  Adverse reactions resulting in permanent discontinuation of JIDEYTRO occurring in ≥2 patients were pneumonia (0.7%) and pneumonitis (0.5%).

Dosage interruptions of JIDEYTRO due to an adverse reaction occurred in 30% of patients. Adverse reactions which required dosage interruption in ≥1% of patients included pneumonia (4.6%), increased creatine phosphokinase level (3.0%), peripheral neuropathy (1.9%), peripheral edema (1.6%), COVID-19 (1.4%), and dyspnea and elevated alanine aminotransferase level (each in 1.2%).

Dose reductions of JIDEYTRO due to an adverse reaction occurred in 10% of patients. Adverse reactions which required dosage reduction in ≥1% of patients included peripheral edema (1.9%) and peripheral neuropathy (1.2%).

Table 3 summarizes the adverse reactions that occurred in the ARROS-1 trial.

Clinically relevant adverse reactions in <10% of patients receiving JIDEYTRO were cognitive disorders, psychiatric disorders, stomatitis, ataxia, ILD/pneumonitis, QTc prolongation, pancreatitis, and ankle fracture.

Table 4 summarizes the laboratory abnormalities in ARROS-1.

Strong and Moderate CYP3A Inhibitors

Avoid concomitant use of JIDEYTRO with a strong or moderate CYP3A inhibitor.

Zidesamtinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inhibitor increases zidesamtinib exposure [see Clinical Pharmacology (12.3)], which may increase the risk of JIDEYTRO adverse reactions.

Strong and Moderate CYP3A Inducers

Avoid concomitant use of JIDEYTRO with strong or moderate CYP3A inducers.

Concomitant use of JIDEYTRO with a strong or moderate CYP3A inducer may decrease zidesamtinib exposure [see Clinical Pharmacology (12.3)], which may decrease the effectiveness of JIDEYTRO.

Risk Summary

Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], JIDEYTRO can cause fetal harm when administered to a pregnant woman. There are no available data on JIDEYTRO use in pregnant women to inform a drug-associated risk. Oral administration of zidesamtinib to pregnant rats during the period of organogenesis resulted in embryo-fetal mortality, alterations to growth, and structural abnormalities at maternal exposures approximately equivalent to the human exposure at the recommended dose based on AUC (see Data). Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Human Data

Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis.

Animal Data

In an embryo-fetal development study, pregnant rats received oral doses of 3, 8, or 30 mg/kg/day of zidesamtinib during the period of organogenesis (gestation day 6 to 17). Zidesamtinib caused decreased fetal body weight, visceral malformations (absent kidneys and ureter), and an increase in the incidence of skeletal variations, including misshapen sternebra and cervical arch and incomplete ossification of the sternebra and thoracic centrum at 3 mg/kg/day (approximately 1.4 times the human exposure at the recommended dose based on AUC). Zidesamtinib resulted in complete litter resorption (post-implantation loss) at doses ≥8 mg/kg/day (approximately ≥3.5 times the human exposure at the recommended dose based on AUC).

Risk Summary

There are no data on the presence of JIDEYTRO in human milk or their effects on either a breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with JIDEYTRO and for 1 week after the last dose.

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

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating JIDEYTRO [see Use in Specific Populations (8.1)].

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with JIDEYTRO and for 6 months after the last dose.

Males

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with JIDEYTRO and for 3 months after the last dose [see Nonclinical Toxicology (13.1)].

Infertility

Based on findings from animal studies, JIDEYTRO may impair fertility in males and females. The effects on male fertility were reversible. The reversibility of the effect on fertility in females is unknown [see Nonclinical Toxicology (13.1)].

The safety and effectiveness of JIDEYTRO in pediatric patients has not been established.

Juvenile Animal Data

Daily oral administration of zidesamtinib to juvenile rats from postnatal day 7 to 28 (approximately equal to a human pediatric age of a neonate to child) resulted in ocular toxicity, including hemorrhage, corneal ulcers, rupture, and vision loss at 8 mg/kg/day (approximately 2.4 times the human exposure based on AUC at the recommended dose).

Of the 446 patients who received JIDEYTRO, 21.5% were 65 to 74 years old, and 8% were 75 years of age or older. There were no clinically meaningful differences in safety and efficacy between patients younger than 65 years of age and patients 65 years of age or older.

The effect of severe renal impairment (eGFR <30 mL/min) or dialysis on zidesamtinib pharmacokinetics is unknown.

No dosage modification is recommended for patients with eGFR 30 to 90 mL/min [see Clinical Pharmacology (12.3)].

The effect of severe hepatic impairment (total bilirubin >3 times ULN with any AST) on the zidesamtinib pharmacokinetics is unknown.

No dosage modification is recommended for patients with mild (total bilirubin >1 to 1.5 times ULN or AST > ULN) or moderate (total bilirubin >1.5 to 3 times ULN with any AST) hepatic impairment [see Clinical Pharmacology (12.3)].

Zidesamtinib is a kinase inhibitor. The molecular formula for zidesamtinib is C₂₂H₂₂FN₇O and the molecular weight is 419.46 Daltons. The chemical name is (R)-3-Ethyl-16-fluoro-10-methyl-19-methyl-20-oxa-3,4,9,10,11,23-hexaazapentacyclo[19.3.1.0^2,6.0^8,12.0^13,18]pentacosa-1(24),2(6),4,8,11,13,15,17,21(25),22-decaen-22-ylamine. The chemical structure of zidesamtinib is as follows:

Zidesamtinib Chemical Structure (Zidesamtinib Chemical Structure)

Zidesamtinib is a white to tan powder with a pKa of 4.89. The aqueous solubility of zidesamtinib at 37°C is pH dependent, decreasing from 25 mg/mL at pH 2.5 to less than 0.1 mg/mL at pH 7.9. The log of the distribution coefficient (octanol/water) at pH 7.4 is 3.01.

JIDEYTRO (zidesamtinib) tablets for oral use are supplied as 25 mg and 100 mg dosage strengths. JIDEYTRO tablets, 25 mg are film-coated, oblong, pink tablets, debossed with "25" on one side and "ZDS" on the other side of the tablet. JIDEYTRO tablets, 100 mg are film-coated, oblong, yellow tablets, debossed with "100" on one side and "ZDS" on the other side of the tablet. Inactive ingredients in the tablet core are hydroxypropyl cellulose, magnesium stearate, mannitol, microcrystalline cellulose and sodium starch glycolate. 

The 25 mg tablet pink film coating contains the inactive ingredients hypromellose, red iron oxide, titanium dioxide, triacetin, and yellow iron oxide. The 100 mg tablet yellow film coating contains the inactive ingredients hypromellose, titanium dioxide, triacetin, and yellow iron oxide.

Zidesamtinib is an inhibitor of tyrosine kinase ROS1, including ROS1 resistance mutations. In a biochemical assay, zidesamtinib inhibited ROS1 (IC₅₀ = 0.7 nM) and also showed inhibitory effects on ALK (IC₅₀ = 3 nM) and tropomyosin receptor kinases (TRKs), TRKB (IC₅₀ = 54 nM), TRKC (IC₅₀ = 193 nM) and TRKA (IC₅₀ = 258 nM).

In vitro, zidesamtinib inhibited the viability of cultured cells expressing ROS1 fusion genes and resistance mutations (G2032R, S1986F, F2004C/V, L2026M, D2033N, and G2101A). In mice subcutaneously implanted with tumors harboring ROS1 fusions, including the G2032R mutation, administration of zidesamtinib resulted in tumor growth inhibition. Zidesamtinib had antitumor activity in an intracranial NSCLC xenograft model harboring a ROS1 fusion.

Exposure-Response Relationships

An increased incidence of dysgeusia was observed with higher metabolite M9 exposure.

Cardiac Electrophysiology

The largest mean increase in QTc interval was 13 ms (upper confidence interval = 19 ms) after administration of JIDEYTRO 100 mg once daily (the maximum recommended dosage) in patients with advanced ROS1-positive NSCLC and other advanced ROS1-positive solid tumors [see Warnings and Precautions (5.2)].

Zidesamtinib pharmacokinetics were observed at steady-state in patients with advanced ROS1-positive NSCLC and other solid tumors at the approved recommended dosage and are presented as mean (coefficient of variation [CV]%) unless otherwise specified. Zidesamtinib maximum plasma concentration (C_max) is 934 ng/mL (44%) and total systemic exposure (AUC) is 8,310 ng.h/mL (37%). Zidesamtinib C_max and AUC increase in a dose proportional manner over the dose range of 25 mg to 100 mg orally once daily (0.25 to 1 times the maximum recommended dosage). Zidesamtinib accumulation is approximately 1.5-fold and steady-state is reached in approximately 4 days.

Absorption

Zidesamtinib median (min, max) time to maximum plasma concentration (T_max) is 1 hour (0.3, 6 hours). Zidesamtinib absolute bioavailability is 83%.

Effect of Food

No clinically significant differences in zidesamtinib exposure were observed in healthy participants following administration of a high fat meal (approximately 1,000 calories with 60% fat).

Distribution

Zidesamtinib apparent (oral) volume of distribution (V_ss) is 326 L (18%).

Zidesamtinib plasma protein binding is 79% and is not concentration-dependent in vitro. Zidesamtinib blood-to-plasma ratio was 0.9 in vitro.

Elimination

Zidesamtinib elimination half-life is 18 (51%) hours with an apparent (oral) clearance of 12 (37%) L/h.

Metabolism

Zidesamtinib is primarily metabolized by CYP3A with minor contributions from CYP1A2 and CYP2C8. An active metabolite, a des-ethyl metabolite (M9), with activity one-third that of the parent, was identified in plasma and its AUC represents 48% of the parent AUC.

Excretion

Following oral administration of a single 100 mg radiolabeled dose to healthy participants, approximately 47% of the dose was recovered in the urine (< 1% unchanged) and 33% in the feces (< 2% as unchanged).

Specific Populations

No clinically meaningful differences in the pharmacokinetics of zidesamtinib were observed based on age (26 to 87 years), sex, race (White 44%, Asian 38%, or Black 4%), body weight (36 to 162 kg), eGFR 30 to 90 mL/min [estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)], or mild (total bilirubin >1 to 1.5 times ULN or AST > ULN) to moderate (total bilirubin >1.5 to 3 times ULN with any AST) hepatic impairment. The effect of severe (total bilirubin >3 x ULN with any AST) hepatic impairment, severe renal impairment (eGFR < 30 mL/min), or dialysis on zidesamtinib pharmacokinetics is unknown.

Drug Interaction Studies

Clinical Studies

Strong CYP3A Inhibitors: Zidesamtinib AUC increased 2.6-fold and C_max increased 1.8-fold following concomitant use of itraconazole (strong CYP3A inhibitor) 200 mg twice daily followed by 200 mg once daily for 6 days.

CYP3A Substrates: No clinically significant differences on midazolam (a sensitive CYP3A substrate) pharmacokinetics were observed when used concomitantly with JIDEYTRO.  

Acid-Reducing Agents: No clinically significant difference in steady-state zidesamtinib pharmacokinetics were observed when used concomitantly with lansoprazole (proton pump inhibitor).

In Vitro Studies

CYP450 Enzymes: Zidesamtinib and M9 do not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or CYP2D6.

UDP-glucuronosyltransferase (UGT): Zidesamtinib does not inhibit UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7 or UGT2B15.

Transporter Systems: Zidesamtinib inhibits P-glycoprotein (P-gp), BCRP, and MATE1. Zidesamtinib does not inhibit OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2 or MATE2K.

M9 does not inhibit P-gp, BCRP, MATE1, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2 or MATE2K.

Carcinogenesis

Carcinogenicity studies with zidesamtinib were not conducted.

Mutagenesis

Zidesamtinib was genotoxic in the in vivo rat micronucleus assays. Zidesamtinib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay or clastogenic in an in vitro assay in human lymphoblastoid TK6 cells.

Zidesamtinib did not induce DNA strand breaks in the comet assay in liver.

Impairment of Fertility

Dedicated fertility studies were not conducted with zidesamtinib. In a 13-week repeat dose toxicity study with oral administration of zidesamtinib in rats, adverse effects in reproductive organs included hemorrhage and inflammation of the ovaries with dilation and inflammation of the oviduct in females at doses ≥3 mg/kg/day (≥1.7 times the human exposure at the recommended dose based on AUC) and spermatid retention and tubular degeneration in the testis in males at doses ≥6 mg/kg/day (approximately equivalent to the human exposure at the recommended dose based on AUC). Findings in males were reversible, whereas the reversibility in females was not assessed.

The efficacy of JIDEYTRO was evaluated in 117 patients with previously treated locally advanced or metastatic ROS1-positive NSCLC who received JIDEYTRO at a dose of 100 mg orally once daily in ARROS-1, a multicenter, single-arm, open-label, multi-cohort clinical trial (NCT05118789). Eligible patients were required to have ROS1-positive locally advanced or metastatic NSCLC, ECOG performance status ≤1, and measurable disease per RECIST v1.1. Patients with asymptomatic, stable intracranial metastases were eligible. Identification of ROS1 gene fusions was determined in local laboratories using next-generation sequencing (NGS), polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH) tests.

The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR) according to RECIST v1.1 as assessed by blinded independent central review (BICR). Intracranial response according to modified RECIST v1.1 was assessed by BICR. Tumor assessments with imaging were performed every 8 weeks for the first 18 months and every 12 weeks thereafter. The efficacy population included 117 patients who received at least 1 prior ROS1 TKI with or without prior platinum-based chemotherapy or immunotherapy.

Among the 117 patients with ROS1 TKI-pretreated NSCLC, the median age was 57 years (range 31 to 83); 56% were female; 47% were White; 36% were Asian; 4% were Black or African American and 13% were unknown or other races; 68% never smoked; and 62% had ECOG performance status of 1 at baseline. At baseline, 100% had metastatic disease; 49% had CNS metastases by BICR; 97% had adenocarcinoma; 52% patients had received prior platinum-based chemotherapy for advanced disease; 50% received 1 prior ROS1 TKI (including crizotinib [47%], entrectinib [46%] and repotrectinib and/or taletrectinib [7%]), and 50% received 2 or more prior ROS1 TKIs (including lorlatinib, repotrectinib and/or taletrectinib [93%]).

Efficacy results are summarized in Table 5.

In patients who received one prior ROS1 TKI (N=59), the overall response rate was 49% (95% CI: 36, 63). In patients who received two or more prior ROS1 TKIs (N=58), including lorlatinib, repotrectinib and/or taletrectinib, the overall response rate was 38% (95% CI: 26, 52).

Fifty patients had measurable CNS metastases at baseline as assessed by BICR and had not received radiation therapy to the brain within 2 months prior to study entry; responses were observed in 48% (95% CI: 34, 63) of patients including 22% of patients with a complete response.

Responses were observed in 21 of the 42 (50%) patients who had ROS1 resistance mutations. Of the 26 patients with the solvent front G2032R resistance mutation, responses were observed in 14 patients (54%). Responses were also observed in patients with other mutations (ROS1G2032K, ROS1D2033N, ROS1F2004C/V, ROS1G1957A).

How Supplied

JIDEYTRO (zidesamtinib) is supplied as follows:

Storage and Handling

Store JIDEYTRO at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].

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

Central Nervous System Adverse Reactions

Advise patients of the risk of central nervous system (CNS) adverse reactions during treatment with JIDEYTRO and to inform their healthcare provider if they experience new or worsening CNS symptoms. Advise patients to avoid engaging in hazardous tasks that require mental alertness and motor coordination such as operating machinery or driving a motor vehicle if they are experiencing CNS reactions [see Warnings and Precautions (5.1)].

QTc Prolongation

Advise patients of the risks of QTc interval prolongation during treatment with JIDEYTRO. Advise patients to contact their healthcare provider immediately to report signs or symptoms of arrhythmias [see Warnings and Precautions (5.2)].

Interstitial Lung Disease/Pneumonitis

Advise patients of the risks of ILD/pneumonitis during treatment with JIDEYTRO. Advise patients to inform their healthcare provider if they experience new or worsening pulmonary symptoms indicative of ILD/pneumonitis [see Warnings and Precautions (5.3)].

Skeletal Fractures

Advise patients that bone fractures have occurred in patients taking JIDEYTRO and to report signs or symptoms of fracture to their healthcare provider [see Warnings and Precautions (5.4)].

Myalgia with Creatine Phosphokinase Elevation

Advise patients that JIDEYTRO can cause creatine phosphokinase (CPK) elevations. Advise patients to inform their healthcare provider if they experience muscle pain [see Warnings and Precautions (5.5)].

Pancreatic Toxicity

Advise patients that JIDEYTRO can cause pancreatic toxicity and to contact their healthcare provider if they experience abdominal pain or other symptoms suggestive of pancreatitis [see Warnings and Precautions (5.6)].

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 (5.7), Use in Specific Populations (8.1, 8.3)]. 
• Advise females of reproductive potential to use effective contraception during treatment with JIDEYTRO and for 6 months after the last dose [see Use in Specific Populations (8.1, 8.3)].
• Advise male patients with female partners of reproductive potential to use effective contraception during treatment with JIDEYTRO and for 3 months after the last dose [see Use in Specific Populations (8.3)].

Lactation

Advise females not to breastfeed during treatment with JIDEYTRO and for 1 week after the last dose [see Use in Specific Populations (8.2)].

Infertility

Advise males and females of reproductive potential that JIDEYTRO may impair fertility [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)].

Drug Interactions

Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions (7)].

Distributed by: Nuvalent Inc., Cambridge MA  02142 USA

JIDEYTRO™ is a trademark of Nuvalent Inc.

07/2026

Jideytro 25 mg Carton (Jideytro 25mg Ct)

Principle Display Panel

NDC 85001-101-01          RX ONLY

Jideytro™(zidesamtinib) tablets

25 mg

Swallow tablets whole
Do not break, crush or chew tablets

30 Film-coated
tablets

Jideytro 25 mg Container Label (Jideytro 25mg Lb)

Manufactured for and Distriburted by:
Nuvalent, Inc.
Cambridge, MA 02142 USA
Jideytro™ is a trademark of
Nuvalent, Inc.               Product of China

NDC 85001-101-01       RX ONLY

Jideytro™
(zidesamtinib) tablets

25 mg

                                   Swallow
                                   tablets whole
                                   Do not break, crush
                                   or chew tablets

Each tablet contains 25 mg zidesamtinib

Recommended Dosage:
See Prescribing Information

Storage: Store at 20°C to
25°C (68°F to 77°F);
excursions permitted
between 15°C to 30°C
(59°F to 86°F)
[see USP Controlled
Room Temperature]

Keep out of reach
of children

Jideytro 100 mg Carton (Jideytro 100mg Ct)

Principle Display Panel

NDC 85001-102-01             RX ONLY

Jideytro™
(zidesamtinib) tablets

100 mg

Swallow tablets whole
Do not break, crush or chew tablets

30 Film-coated
tablets

Jideytro 100 mg Container Label (Jideytro 100mg Lb)

Manufactured for and Distriburted by:
Nuvalent, Inc.
Cambridge, MA 02142 USA
Jideytro™ is a trademark of
Nuvalent, Inc.                  Product of China

NDC 85001-102-01          RX ONLY

Jideytro™
(zidesamtinib) tablets

100 mg

Swallow
tablets whole
Do not break, crush
or chew tablets

Each tablet contains
100 mg zidesamtinib

Recommended Dosage:
See Prescribing Information

Storage: Store at 20°C to
25°C (68°F to 77°F);
excursions permitted
between 15°C to 30°C
(59°F to 86°F)
[see USP Controlled
Room Temperature]

Keep out of reach
of children