Taletrectinib adipate, an inhibitor of proto-oncogene tyrosine protein kinase-1 (ROS1), is an antineoplastic agent.1
Taletrectinib adipate is used for the treatment of locally advanced or metastatic ROS1 -positive non-small cell lung cancer (NSCLC) in adult patients.1, 5 The presence of ROS1 rearrangement in tumor specimens should be confirmed prior to initiation of therapy.1 An FDA-approved test to detect ROS1 rearrangement for selecting patients for treatment with taletrectinib is not currently available.1 Taletrectinib has been designated an orphan drug by FDA for the treatment of ROS1 -positive, neurotrophic receptor tyrosine kinase (NTRK) -positive, anaplastic lymphoma kinase (ALK) -positive, leukocyte tyrosine kinase (LTK) -positive, activated Cdc42-associated kinase 1 (ACK1) -positive, or discoidin domain receptor 1 (DDR1) -positive NSCLC.2
The current indication for taletrectinib in the treatment of ROS1 -positive locally advanced or metastatic NSCLC is based principally on the results of 2 multicenter, single-arm, open-label, phase 2 studies (TRUST-I and TRUST-II).1, 3, 4 In both trials, patients had histologically confirmed, locally advanced or metastatic, ROS1 -positive NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.1 Identification of ROS1 gene fusions in tumor specimens was determined in local laboratories using next-generation sequencing (NGS), polymerase chain reaction (PCR), fluorescence in situ (FISH), or immunohistochemistry (IHC).1 Efficacy was evaluated in a total of 270 patients who received taletrectinib 600 mg orally once daily.1, 3, 4
The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR) according to RECIST v1.1 as assessed by a blinded independent central review (BICR).1 For patients with measurable baseline intracranial metastases, intracranial response according to modified RECIST v1.1 was also assessed by the BICR.1 Tumor assessments using imaging were conducted every 6 weeks during the initial 24 weeks, every 9 weeks over the subsequent year, and every 12 weeks thereafter.1 The efficacy populations included 157 patients naïve to treatment with a ROS-1 TKI and 113 patients who received one prior ROS1 TKI.1 Patients were chemotherapy-naïve or previously treated with chemotherapy for locally advanced disease.1
Among the 103 patients with ROS1 TKI-naïve NSCLC treated in TRUST-I, the median age was 56 years (range 26-78 years); 55% were female, all patients were Asian, 73% never smoked, and 81% had an ECOG performance status of 1.1 At baseline, 91% had metastatic disease, 17% had CNS metastases as assessed by the BICR, 96% had adenocarcinoma histology, and 19% had received prior platinum-based chemotherapy for advanced disease.1
Among the 54 patients with ROS1 TKI-naïve NSCLC treated in TRUST-II, the median age was 57 years (range 27-82 years); 56% were female, 65% were Asian, 22% were White, 1.9% were Black or African American, and 11% were of unknown race; 1.9% were of Hispanic or Latino ethnicity, 50% never smoked, and 61% had an ECOG performance status of 1.1 At baseline, 91% of patients had metastatic disease, 35% had CNS metastases as assessed by BICR, 98% had adenocarcinoma histology, and 19% had received prior platinum-based chemotherapy for advanced disease.1
Among the 103 ROS1 TKI-naïve patients in TRUST-I and 54 patients in TRUST-II, the ORR was 90% and 85%, respectively.1 In TRUST-I, a complete response was achieved in 5% of patients and a partial response in 85%.1 In TRUST-II, 7% of patients achieved a complete response and 78% achieved a partial response.1 The median DOR was not reached in TRUST-I and was not included in TRUST-II due to the shorter median follow-up duration of 19 months.1, 6 Among ROS1 TKI-naïve patients across both trials, 15 patients had measurable CNS metastases at baseline and had not received radiation therapy to the brain within 2 months prior to study entry.1 Intracranial responses were observed in 11 patients.1
Among the 66 patients with ROS1 TKI-pretreated NSCLC in TRUST-I, the median age was 51 years (range 31-77 years); 61% were female, all patients were Asian, 74% never smoked, and 71% had an ECOG performance status of 1.1 At baseline, 97% had metastatic disease, 42% had CNS metastases as assessed by BICR, 92% had adenocarcinoma histology, 35% had received prior platinum-based chemotherapy for advanced disease, and all patients had received prior treatment with crizotinib.1
Among the 47 patients with ROS1 TKI-pretreated NSCLC in TRUST-II, the median age was 55 years (range 27-79 years); 57% were female, 47% were Asian, 34% were White, 2.1% were Black or African American, 17% were of unknown or other races, and 2.1% were of Hispanic or Latino ethnicity.1 A total of 62% of patients never smoked and 55% had an ECOG performance status of 1.1 At baseline, 98% had metastatic disease, 57% had CNS metastases as assessed by BICR, 98% had adenocarcinoma histology, 40% received prior platinum-based chemotherapy for advanced disease, 79% had been previously treated with crizotinib, and 21% had been previously treated with entrectinib.1
Among the 66 patients with ROS1 TKI-pretreated in TRUST-I and 47 in TRUST-II, the ORR was 52% and 62%, respectively.1 In TRUST-I, a complete response was not achieved by any patients and 52% achieved a partial response.1 In TRUST-II, 11% of patients achieved a complete response and 51% achieved a partial response.1 The median DOR in TRUST-I was 13.2 months and was not included in TRUST-II due to the shorter median follow-up duration of 19 months.1, 6 Among the ROS1 TKI-pretreated patients across both trials, 24 had measurable CNS metastases at baseline as assessed by the BICR and had not received radiation therapy to the brain within 2 months prior to study entry.1 Intracranial responses were observed in 15 patients.1
Of the 32 patients who had re-biopsied samples analyzed by next-generation sequencing after progression on a prior ROS1 TKI, 15 were found to have resistance mutations.1 Responses were observed in 8 of these 15 patients, all of whom had tumors with the solvent front mutation G2032R.1
The American Society of Clinical Oncology (ASCO) guidelines on management of stage IV NSCLC with driver alterations addresses treatment of patients harboring ROS1 mutations.7 According to ASCO, first-line treatment recommendations for patients with stage IV NSCLC and ROS1 mutations include repotrectinib, entrectinib, and crizotinib.7 Ceritinib or lorlatinib may be given when these therapies are not available or not tolerated.7 Repotrectinib is also recommended as a second-line therapy in patients who were previously treated with entrectinib, crizotinib, ceritinib, or lorlatinib.7 Taletrectinib is not discussed since the drug was approved after the guideline was published.2, 7
Taletrectinib is administered orally as capsules.1 The drug should be taken at approximately the same time each day without food (no food intake at least 2 hours before and 2 hours after taking taletrectinib).1
Swallow capsules whole; do not open, crush, chew, or dissolve the capsule prior to swallowing.1
If a dose of taletrectinib is missed, take the next dose at its scheduled time on the following day.1
If a dose of taletrectinib is vomited after administration, an additional dose should not be administered to replace the vomited dose.1 The next dose should be administered at the next scheduled time.1
Minimize sun exposure and use sun protection, including broad-spectrum sunscreen, during treatment and for at least 5 days after discontinuing treatment.1
Store capsules at 20-25ºC; excursions permitted between 15-30ºC.1
Dosage of taletrectinib adipate is expressed in terms of taletrectinib.1
The recommended adult dosage of taletrectinib for the treatment of ROS1 -positive locally advanced or metastatic NSCLC is 600 mg once daily.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Dosage Modification for Adverse Reactions
Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of taletrectinib may be necessary in patients experiencing certain adverse effects.1 When necessary, the dosage of taletrectinib should be reduced as described in Table 1.1 Permanently discontinue taletrectinib capsules in patients unable to tolerate 200 mg once daily.1
Dosage Reduction | Recommended Dosage |
|---|---|
First dose reduction | 400 mg once daily |
Second dose reduction | 200 mg once daily |
The recommended dosage modifications of taletrectinib for the management of adverse reactions are provided in Table 2.1
Adverse Reaction | Dosage Modification Based on Severity |
|---|---|
Hepatotoxicity (Elevation of ALT or AST) | Grade 3 (>5-20 times ULN): Withhold until recovery to Grade ≤1 or baseline. If resolved within 6 weeks, resume at a reduced dose level. If unresolved after 6 weeks, permanently discontinue. Recurrence of Grade 3: If resolved within 6 weeks, resume at a reduced dose level. If unresolved after 6 weeks, permanently discontinue. Grade 4 (>20 times ULN): Withhold until recovery to Grade ≤1 or baseline. If resolved within 6 weeks, resume at a reduced dose level. If unresolved after 6 weeks, permanently discontinue. Recurrence of Grade 4: Permanently discontinue. ALT or AST ≥3 times ULN with concurrent total bilirubin ≥2 times ULN (in the absence of cholestasis or hemolysis): Permanently discontinue. |
ILD/pneumonitis | Grade 1: Withhold if ILD/pneumonitis occurs or is suspected until recovery to Grade 0 or baseline. If resolved within 6 weeks, resume at the same dose level. If unresolved after 6 weeks, permanently discontinue. Grade 2: Withhold if ILD/pneumonitis occurs or is suspected until recovery to Grade 0 or baseline. If resolved within 6 weeks, resume at a reduced dose level. If unresolved after 6 weeks, permanently discontinue. Recurrence of Grade 1 or Grade 2: Permanently discontinue. Grade 3 or 4: Permanently discontinue. |
QTc Interval Prolongation | Grade 2 (QTc interval 481-500 millisecond): Withhold until recovery to Grade ≤1 or baseline. Correct electrolytes and/or change concomitant medications. Resume at same dose. Grade 3 (QTc interval ≥501 millisecond or QTc interval increase of >60 millisecond from baseline): Withhold until recovery to Grade ≤1 or baseline. Correct electrolytes and/or change concomitant medications. Resume at a reduced dose. Grade 4 (Torsade de pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrhythmia): Permanently discontinue. |
Hyperuricemia | Grade 3 or 4: Withhold until improvement of signs or symptoms. Resume at same or reduced dose level or permanently discontinue. |
Creatine Phosphokinase Elevation | CPK elevation >5 times ULN: Withhold until recovery to baseline or ≤2.5 times ULN, then resume at same dose. CPK elevation >10 times ULN or second occurrence of CPK elevation of >5 times ULN: Withhold until recovery to baseline or ≤2.5 times ULN, then resume at a reduced dose. |
Other Adverse Reactions | Grade 3: Withhold until recovery to Grade ≤1 or baseline. If resolved within 6 weeks, resume at a reduced dose level. If unresolved after 6 weeks, permanently discontinue. Recurrence: Resume treatment at a reduced dose or permanently discontinue. Grade 4: Withhold until recovery to Grade ≤1 or baseline. Resume at reduced dose or permanently discontinue as clinically indicated. Recurrence: Permanently discontinue. |
No dosage adjustment of taletrectinib is required for patients with mild (total bilirubin >1-1.5 times ULN or AST greater than ULN) hepatic impairment.5
The recommended dosage of taletrectinib has not been established in patients with moderate (total bilirubin >1.5-3 times ULN with any AST) or severe (total bilirubin >3 times ULN with any AST) hepatic impairment.5
No dosage adjustment of taletrectinib is required for patients with mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-89 mL/minute).5
The effects of severe renal impairment, end-stage renal disease, or dialysis on pharmacokinetics of taletrectinib have not been established.5
Dosage adjustments based on age are not required.1
Hepatotoxicity, including drug-induced liver injury and fatal adverse reactions can occur in patients treated with taletrectinib.1 In patients receiving taletrectinib in clinical trials, increased AST occurred in 88% of patients, including 10% of patients with Grade 3 or 4.1 Increased ALT occurred in 85% of patients, including 13% with Grade 3 or 4.1 The median time to first onset of AST or ALT elevation was 15 days (range, 3 days to 20.8 months).1 Increased AST or ALT each led to dose interruptions in 7% of patients.1 Dose reductions due to increased AST and ALT occurred in 5% and 9% of patients, respectively.1 Permanent discontinuation of taletrectinib due to elevated AST or ALT each occurred in 0.3% of patients.1 Other liver-related events leading to permanent discontinuation included hepatotoxicity (0.6%) and elevated bilirubin (0.3%).1
Concurrent elevations of AST or ALT ≥3 times the upper limit of normal (ULN) and total bilirubin ≥2 times the ULN, with normal alkaline phosphatase, were observed in 2 patients (0.6%) receiving taletrectinib.1 Fatal liver events occurred in 2 patients (0.6%).1
Monitor liver function tests (AST, ALT, and bilirubin) prior to initiating taletrectinib, every 2 weeks during the first 2 months of treatment, and then monthly thereafter as clinically indicated with more frequent testing in patients who develop transaminase elevations.1 Withhold, then resume at reduced dose upon improvement, or permanently discontinue treatment based on severity.1
Interstitial Lung Disease (ILD)/Pneumonitis
Life-threatening, or fatal ILD or pneumonitis can occur in patients treated with taletrectinib.1 In patients receiving taletrectinib in clinical trials, ILD/pneumonitis occurred in 2.3% of patients, including Grade 3 or 4 in 1.1% of patients.1 The median time to first onset of ILD/pneumonitis was 3.8 months (range, 12 days to 11.8 months).1
ILD/pneumonitis led to dose interruptions in 1.1% of patients.1 Dose reduction and permanent discontinuation due to ILD/pneumonitis each occurred in 0.6% of patients.1 A single fatal case occurred in a patient who received taletrectinib 400 mg once daily.1
Monitor patients for new or worsening pulmonary symptoms suggestive of ILD/pneumonitis.1 Immediately withhold taletrectinib in patients with suspected ILD/pneumonitis.1 Withhold, then reduce the dose or permanently discontinue taletrectinib if Grade ≥2 ILD/pneumonitis occurs.1
Prolongation of the corrected QT (QTc) interval can occur in patients treated with taletrectinib, which can increase the risk of ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death.1 The prolongation occurs in a plasma concentration-dependent manner.1 Among 351 patients receiving taletrectinib who underwent ≥1 post baseline ECG assessments, 13% had a QTcF increase >60 millisecond from baseline, and 2.6% had QTcF increase to >500 millisecond after receiving taletrectinib.1 Overall, 3.4% of patients experienced Grade ≥3 QTc prolongation.1 The median time from the first dose to the onset of ECG QT prolongation was 22 days (range, 1 day to 38.7 months).1 QTc prolongation led to dose interruption and dose reduction, each in 2.8% of patients receiving taletrectinib.1
Monitor ECGs and electrolytes prior to initiating taletrectinib, and then periodically thereafter as clinically indicated during treatment.1 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.1 Significant QTc interval prolongation may occur when taletrectinib is administered with food, strong or moderate CYP3A inhibitors, or drugs known to prolong the QTc interval.1 Administer taletrectinib on an empty stomach.1 Avoid coadministration with strong or moderate CYP3A inhibitors and/or QTc-prolonging agents.1 Withhold, then resume at the same or reduced dose, or permanently discontinue treatment based on severity.1
Hyperuricemia can occur in patients treated with taletrectinib.1 In patients receiving taletrectinib in clinical trials, hyperuricemia occurred in 14% of patients, with 16% of these patients requiring urate-lowering medication despite no prior history of gout or hyperuricemia.1 Hyperuricemia Grade ≥3 occurred in 1 patient.1 The median time to first onset of hyperuricemia was 2.1 months (range, 7 days to 35.8 months).1 Hyperuricemia resulted in dose interruption in 0.3% of patients.1
Monitor serum uric acid levels prior to initiating taletrectinib and periodically during treatment.1 Initiate treatment with urate-lowering medications as clinically indicated.1 Withhold, then resume at the same or reduced dose, or permanently discontinue treatment based on severity.1
Myalgia with Creatine Phosphokinase Elevation
Myalgia with or without CPK elevation can occur in patients treated with taletrectinib.1 In patients receiving taletrectinib in clinical trials, myalgia occurred in 10% of patients.1 The median time to first onset of myalgia was 11 days (range, 2 days to 10 months).1 Concurrent myalgia with increased CPK occurred in 0.9% of patients within 7 days of treatment.1 Taletrectinib was interrupted in 1 patient (0.3%) with myalgia, who also presented with concurrent CPK elevation.1
Advise patients to report any unexplained muscle pain, tenderness, or weakness.1 Monitor serum CPK levels every 2 weeks during the first month of treatment and then as clinically indicated in patients reporting unexplained muscle pain, tenderness, or weakness.1 Withhold, then resume at the same or reduced dose upon improvement.1
An increased risk of fractures can occur in patients treated with taletrectinib.1 ROS-1 inhibitors as a class have been associated with skeletal fractures.1 In patients receiving taletrectinib in clinical trials, 3.4% of patients experienced fractures, including Grade 3 in 1.4% of patients.1 Fractures involved the ribs (1.4%), spine (0.9%), femur (0.6%), humerus (0.3%), and acetabulum (0.3%).1 The median time to first onset of fracture was 10.7 months (range, 26 days to 29.1 months).1 Fractures led to dose interruption in 0.3% of patients.1
Promptly evaluate patients with signs or symptoms (e.g., pain, changes in mobility, deformity) of fractures.1 There are no data on the effects of taletrectinib on healing of known fractures and risk of future fractures.1
Fetal/Neonatal Morbidity and Mortality
Taletrectinib use during pregnancy can cause fetal harm based on data in humans with congenital mutations leading to changes in tropomyosin receptor tyrosine kinase (TRK) signaling, findings from animal reproduction studies, and the mechanism of action of taletrectinib.1
Oral administration of taletrectinib to pregnant rats and rabbits during the period of organogenesis resulted in structural abnormalities in rats, and both structural abnormalities and embryo-fetal mortality in rabbits.1 Findings in both species occurred at doses resulting in exposures below or equal to the human exposure based on AUC at the recommended dose.1
Advise pregnant women and females of reproductive potential of the potential hazard to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with taletrectinib and for 3 weeks after the last dose.1 Advise males with female partners of reproductive potential to use effective contraception during treatment with taletrectinib and for 3 weeks after the last dose.1
Taletrectinib use during pregnancy can cause fetal harm based on data in humans with congenital mutations leading to changes in TRK signaling, findings from animal reproduction studies, and the mechanism of action of taletrectinib.1 Limited data from case reports with taletrectinib used in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes.1
Oral administration of taletrectinib to pregnant rats and rabbits during organogenesis resulted in embryo-fetal mortalities and structural abnormalities at exposures that were below or equal to the human exposure at the recommended dose.1 Apprise pregnant women of the potential risk to a fetus.1
It is unknown whether taletrectinib is distributed into human milk or if the drug has any effect on milk production or on the breastfed infant.1
Because of the potential for serious adverse reactions in nursing children, advise lactating women not to breastfeed during treatment with taletrectinib and for 3 weeks after the last dose.1
Females and Males of Reproductive Potential
Based on findings from animal studies, use of taletrectinib may impair fertility in both males and females.1 The effects on animal fertility were reversible.1
Verify the pregnancy status of females of reproductive potential prior to starting taletrectinib.1 Advise female patients of reproductive potential to use effective contraception during treatment and for 3 weeks following the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks following the last dose.1
The safety and effectiveness of taletrectinib have not been established in pediatric patients.1
In clinical trials, 25% of patients receiving taletrectinib were 65 years of age or older, while 4% were 75 years of age or older.1 There were no clinically meaningful differences in safety and efficacy between these patients and younger adults1
No clinically important differences in the pharmacokinetics of taletrectinib have been observed based on mild hepatic impairment (total bilirubin >1-1.5 times the upper limit of normal [ULN] or AST greater than ULN).1 The effect of moderate (total bilirubin >1.5-3 times ULN with any AST) or severe (total bilirubin >3 times ULN with any AST) hepatic impairment on taletrectinib pharmacokinetics is unknown.1
No clinically important differences in the pharmacokinetics of taletrectinib have been observed based on mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] 30 to <89 mL/minute).1 The effect of severe renal impairment (eGFR <30 mL/minute) or dialysis on taletrectinib pharmacokinetics is unknown.1
Most common adverse reactions (≥20%) reported with taletrectinib in clinical studies were diarrhea, nausea, vomiting, dizziness, rash, constipation, and fatigue.1
Most common Grade 3 or 4 laboratory abnormalities (≥5%) reported with taletrectinib in clinical studies were increased ALT, increased AST, decreased neutrophils, and increased creatine phosphokinase.1
In vitro, taletrectinib induces cytochrome P-450 (CYP) 1A2 and CYP3A4, and inhibits CYP2C8, CYP2D6, and CYP3A.1
Taletrectinib inhibits P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, multidrug and toxin extrusion (MATE) 1 and MATE2-K.1 Taletrectinib is a substrate of P-gp.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Strong and Moderate CYP3A Inhibitors
Taletrectinib AUC and peak plasma concentration increased by 3.3- and 1.8-fold, respectively, following concomitant use with itraconazole, a strong CYP3A and P-gp inhibitor.1
Taletrectinib AUC and peak plasma concentration is predicted to increase by up to 2.6- and 1.5-fold, respectively, following concomitant use with moderate CYP3A inhibitors (fluconazole, erythromycin, or verapamil).1
Concomitant use of taletrectinib with a strong or moderate CYP3A inhibitor increases taletrectinib exposure, which may increase the risk of taletrectinib adverse reactions.1
Avoid concomitant use with strong or moderate CYP3A inhibitors.1
Strong and Moderate CYP3A Inducers
Taletrectinib AUC and peak plasma concentration are predicted to decrease by 66% and 40%, respectively, following concomitant use with efavirenz, a moderate CYP3A inducer.1
Taletrectinib peak plasma concentrations and AUC decreased by 42% and 86%, respectively, following concomitant use with rifampin, a strong CYP3A and P-gp inducer.1
Concomitant use of taletrectinib with a strong or moderate CYP3A inducer decreases taletrectinib exposure, which may reduce the effectiveness of taletrectinib.1
Avoid concomitant use with strong or moderate CYP3A inducers.1
Substrates of P-glycoprotein Transport
Concomitant use of taletrectinib with digoxin (P-gp substrate) did not result in any clinically significant difference in the exposure of digoxin.1
Drugs that Prolong the QT Interval
Concomitant use of taletrectinib with other drugs known to prolong the QT interval should be avoided due to the increased risk of QTc interval prolongation.1
If concomitant use cannot be avoided, adjust the frequency of monitoring as recommended.1 Withhold treatment with taletrectinib if the QTc interval is >500 milliseconds or the change from baseline is >60 milliseconds.1
Drugs Affecting Gastric Acidity
When the proton-pump inhibitor (PPI) omeprazole was administered concomitantly with taletrectinib, peak plasma concentration and AUC of taletrectinib were decreased by 65% and 40%, respectively.1
Concomitant use of a PPI decreases taletrectinib exposure, which may reduce the effectiveness of taletrectinib.1
Avoid concomitant use with PPIs and histamine (H)2 receptor antagonists.1 Administer locally acting antacids at least 2 hours before or 2 hours after taking taletrectinib.1
Avoid food or drink containing grapefruit during treatment with taletrectinib.1
Taletrectinib is an inhibitor of tyrosine kinase ROS-1 , including ROS-1 resistance mutations.1 Taletrectinib also showed inhibitory effects on tropomyosin receptor kinases (TRKs) TRKA, TRKB, and TRKC.1 ROS-1- fusion proteins can produce hyperactivation of downstream signaling pathways, leading to unconstrained cell proliferation and tumorigenic potential.1 Taletrectinib exhibited anti-tumor activity in cancer cells expressing ROS-1 fusions and mutations.1 It also inhibited cell proliferation in mice expressing the G2032R mutation.1 Additionally, taletrectinib demonstrated anticancer activity in an intracranial non-small cell lung cancer (NSCLC) xenograft model with a ROS-1 fusion.1
Taletrectinib exposure-response relationships for efficacy and the time course of pharmacodynamic response have not been fully characterized.1 Higher taletrectinib exposure is associated with an increased risk of Grade ≥3 elevations in AST and ALT levels.1
Taletrectinib time to maximum plasma concentration is 2-6 hours, and steady state concentration is reached within 7 days.1 AUC and peak plasma concentrations increased by 1.5-fold when taletrectinib was administered with a high-fat meal (1000 calories, 50% fat).1 In vitro, taletrectinib protein binding is concentration dependent and decreases with increasing drug concentrations.1 Taletrectinib effective half-life is approximately 66 hours.1 Taletrectinib is metabolized through both cytochrome (CYP) 450-mediated and non-CYP450 pathways, including sulfation and acetylation.1 CYP3A is the predominant CYP450 enzyme involved in the metabolism of taletrectinib, with CYP2C8 and CYP2C9 contributing to a lesser extent.1 Following a single oral dose of taletrectinib 200 mg, 75% of the dose was recovered in feces (15% as unchanged) and 11% in urine (2.9% as unchanged).1 Taletrectinib AUC was approximately 30% higher in Asian patients compared to White patients.1 No clinically significant differences in AUC were observed between White and Black patients.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Taletrectinib is available only from designated specialty pharmacies.8 Contact the manufacturer or consult the taletrectinib website ([Web]) for more information.8
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 200 mg (of taletrectinib) | Ibtrozi® | Nuvation Bio |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions October 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Nuvation Bio Inc. IBTROZI® (taletrectinib) ORAL prescribing information. 2025 Jun. [Web]
2. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2025 Jul 17.
3. Li W, Xiong A, Yang N, et al. Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study. J Clin Oncol. 2024;42(22):2660-2670.
4. Nagasaka M, Ohe Y, Zhou C, et al. TRUST-II: a global phase II study of taletrectinib in ROS1-positive non-small-cell lung cancer and other solid tumors. Future Oncol. 2023;19(2):123-135.
5. US Food and Drug Administration. Center for Drug Evaluations and Research Application Number: 219713Orig1s000 Multi-Discipline Review. From the FDA website. Accessed 2025 Jul 17.
6. Efficacy. From Ibtrozi website. Accessed 2025 Aug 21. [Web]
7. Reuss JE, Kuruvilla S, Ismaila N, et al. Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2025.1. J Clin Oncol. 2025;43(24):e31-e44. doi:10.1200/JCO-25-01061
8. Support and access. From Ibtrozi website. Accessed 2025 Aug 21. [Web]