JIDEYTRO study design
ARROS-1: The only ROS1 trial that allowed 1-4 prior TKIs, including all currently approved agents1-6
ARROS-1 was a global, single-arm, open-label, multi-cohort Phase 1/2 clinical trial.1,7
Pivotal efficacy population1,2*:
ROS1 TKI-pretreated NSCLC†; N=117. Patients received a range of 1-4 prior ROS1 TKIs.
Primary endpoint1,7:
ORR by BICR
Key inclusion criteria1,7:
- Age ≥18 years
- Locally advanced or metastatic ROS1+ NSCLC
- Evaluable (Phase 1) or measurable (Phase 2) disease per RECIST v1.1
- Prior anticancer treatment‡
- Adequate organ function and bone marrow reserve
- ECOG PS of ≤1
Key secondary endpoints1,7,8:
DOR, icORR, icDOR, safety
Key exclusion criteria7:
- Major surgery within 4 weeks of first study dose
- Ongoing systemic therapy or direct medical intervention for another therapeutic clinical study
- Ongoing anticancer therapy
- *Treated by May 31, 2024; intended to ensure opportunity for ≥6 months DOR follow-up.2
- †Efficacy was evaluated in a subset of 117 patients with previously treated locally advanced or metastatic ROS1+ NSCLC who received JIDEYTRO at a dose of 100 mg once daily.1
- ‡The efficacy-evaluable population included patients who received at least 1 prior ROS1 TKI with or without prior platinum-based chemotherapy or immunotherapy.1
JIDEYTRO was studied in a broad range of TKI-pretreated patients with ROS1+ NSCLC1
Key patient characteristics
50% 1 prior TKI¹
50% 2 prior TKIs¹
2 median lines
of prior anticancer therapy2 (range, 1-11)
49%
CNS metastases
36%
ROS1 resistance mutations¹
Baseline characteristics of patients with prior ROS1 TKI therapy (N=117)1,2
Baseline characteristics*
Age, years, median (range)
57 (31–83)
Female
66 (56%)
Race
White
55 (47%)
Asian
42 (36%)
Black or African American
5 (4%)
Unknown or other races
15 (13%)
ECOG PS 1
72 (62%)
CNS metastases by BICR
57 (49%)
ROS1 resistance mutations
42 (36%)
Prior lines of anticancer therapy, median (range)
2 (1–11)
Prior platinum-based chemotherapy
61 (52%)
Prior TKI treatment history (range, 1–4)*
1 prior TKI
59 (50%)
Crizotinib
28 (47%)
Entrectinib
27 (46%)
Repotrectinib or taletrectinib
4 (7%)
≥2 prior TKIs
58 (50%)
Lorlatinib, repotrectinib, and/or taletrectinib
54 (93%)
- *All data are presented as n (%) except where indicated; age and prior lines of anticancer therapy are presented as median (range).1,2
See durable efficacy* in the pivotal study population.
- *Durable efficacy is based on the overall response rate and the 12-month duration of response rate in the All TKI-pretreated population.1
Discover the safety profile
Learn about the safety and adverse reactions of JIDEYTRO.
Ordering JIDEYTRO for your patients
See ordering details to get your patients started on JIDEYTRO.
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BICR=blinded independent central review; CNS=central nervous system; DOR=duration of response; ECOG PS=Eastern Cooperative Oncology Group performance status; icDOR=intracranial duration of response; icORR=intracranial overall response rate; NSCLC=non-small cell lung cancer; ORR=overall response rate; RECIST v1.1=Response Evaluation Criteria in Solid Tumors v1.1; ROS1+=ROS proto-oncogene 1-positive; TKI=tyrosine kinase inhibitor.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS:
Warnings and Precautions reflect the pooled safety population (N=446) who received JIDEYTRO at a dose of
Central Nervous System (CNS) Adverse Reactions (AR):
- Dizziness, ataxia, cognitive and psychiatric disorders occurred in 25% of patients; 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; of these, 0.2% were Grade 3. Dosage interruption for dizziness was required in 0.4% and dose reduction in 0.7% of patients.
- Ataxia, including gait disturbance and balance disorder, occurred in 2% of patients; all were Grade 1 or 2.
- Cognitive impairment occurred in 9% of patients; 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%), and slow speech (0.2%). Dose interruption for cognitive impairment was required in 1.3% of patients.
- Psychiatric disorders occurred in 6% of patients; 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%). Dosage interruption for psychiatric disorders was required in 0.9% of patients.
- 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.
QTc Interval Prolongation:
- 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.
- 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. QTc prolongation led to dose interruption in 0.4% of patients.
- 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.
Interstitial Lung Disease (ILD)/Pneumonitis:
- JIDEYTRO can cause severe or life-threatening ILD or pneumonitis.
- ILD/pneumonitis occurred in 1.8% of patients, including Grade 3 or 4 in 0.4%.
- ILD/pneumonitis led to dose interruption in 0.7%, dose reduction in 0.2%, and permanent discontinuation 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.
Skeletal Fractures:
- JIDEYTRO can increase the risk of skeletal fractures.
- Five patients (1.1%) experienced skeletal fractures. Grade 3 ankle fractures occurred in two patients (0.4%). Dose interruptions for fractures occurred in 0.4% of patients.
- Promptly evaluate patients with signs or symptoms of fractures.
Myalgia with Creatine Phosphokinase (CPK) Elevation:
- JIDEYTRO can cause myalgia with creatine phosphokinase (CPK) elevation.
- Myalgia occurred in 13% of patients. Based on laboratory values, concurrent myalgia with increased CPK occurred in 2.1% of patients.
- 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 JIDEYTRO at the same or reduced dose, or permanently discontinue JIDEYTRO based on severity.
Pancreatic Toxicity:
- JIDEYTRO can cause pancreatic toxicity. In the pooled safety population, among the subgroup of patients who underwent pancreatic lab testing, increased amylase and lipase levels occurred in 22%, and 25% respectively, with Grade 3 increased lipase in 8% of patients. Grade 3 lipase elevation resulted in JIDEYTRO dose reduction in one patient. In the pooled safety population, Grade 3 pancreatitis occurred in one patient (0.2%).
- 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.
Embryo-Fetal Toxicity:
- 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.
- 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.
ADVERSE REACTIONS:
- The most common adverse reactions (≥15%) were edema, peripheral neuropathy, constipation, fatigue, and dyspnea.
- The most common Grade 3 or 4 laboratory abnormalities (≥2%) were increased lipase, increased CPK, increased triglycerides, decreased lymphocytes, and decreased hemoglobin.
- 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.
DRUG INTERACTIONS:
Strong and Moderate CYP3A Inhibitors:
- Avoid concomitant use of JIDEYTRO with a strong or moderate CYP3A inhibitor as this could increase JIDEYTRO exposure, 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 as this could decrease JIDEYTRO exposure, which may decrease the effectiveness of JIDEYTRO.
INDICATION
JIDEYTRO™ (zidesamtinib) 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.
Please see Full Prescribing Information.
References:
- JIDEYTRO. Prescribing Information. Nuvalent Inc.; 2026.
- Nuvalent. Data on File.
- Drilon A, Siena S, Dziadziuszko R, et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1–2 trials. Lancet Oncol. 2020;21(2):261–270. doi:10.1016/S1470-2045(19)30690-4
- Drilon A, Camidge DR, Lin JJ, et al. Repotrectinib in ROS1 fusion–positive non–small-cell lung cancer. N Engl J Med. 2024;390(2):118–131. doi:10.1056/NEJMoa2302299
- 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. doi:10.1200/JCO.24.00731
- Pérol M, Li W, Pennell NA, et al. Taletrectinib in ROS1+ non–small cell lung cancer: TRUST. J Clin Oncol. 2025;43(16):1920–1929. doi:10.1200/JCO-25-00275
- A study of zidesamtinib (NVL-520) in patients with advanced NSCLC and other solid tumors harboring ROS1 rearrangement (ARROS-1). ClinicalTrials.gov identifier: NCT05118789. Updated October 24, 2025. Accessed July 9, 2026. https://clinicaltrials.gov/study/NCT05118789
- A Phase 1/2 study of the highly selective ROS1 inhibitor NVL-520 in patients with advanced NSCLC and other solid tumors (ARROS-1). EUCT identifier: 2024-511793-71-00. Accessed July 6, 2026. https://euclinicaltrials.eu/ctis-public/view/2024-511793-71-00