A Phase 1/2 interventional study of Zidesamtinib (NVL-520) in Locally Advanced Solid Tumor and Metastatic Solid Tumor, sponsored by Nuvalent Inc.. Recruiting at 63 sites in 14 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-09-24.
Sponsored by Nuvalent Inc. · Phase 1/2, Interventional, and Treatment
Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of zidesamtinib (NVL-520), determine the recommended phase 2 dose (RP2D), and evaluate the antitumor activity in patients with advanced ROS1-positive (ROS1+) NSCLC and other advanced ROS1-positive solid tumors.
Phase 1 will determine the RP2D and, if applicable, the maximum tolerated dose (MTD) of zidesamtinib in patients with advanced ROS1-positive solid tumors.
Phase 2 will determine the objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) of zidesamtinib at the RP2D. Secondary objectives will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and clinical benefit rate (CBR) of zidesamtinib in patients with advanced ROS1-positive NSCLC and other solid tumors.
In Phase 2, study patients will be enrolled into 5 distinct expansion cohorts:
4,040 studies on the registry are indexed under Neoplasm Metastasis; 886 are open to participants now.
This study's planned enrollment of 359 is above the median of 50 across 3,268 interventional studies indexed under Neoplasm Metastasis.
Browse Neoplasm Metastasis studies →Nuvalent Inc. is the lead sponsor of 6 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Disease Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Zidesamtinib (NVL-520) oral daily dosing
Drug: Zidesamtinib (NVL-520)
ROS1+ NSCLC naïve to TKI therapy and up to 1 prior chemotherapy and/or immunotherapy
Drug: Zidesamtinib (NVL-520)
ROS1+ NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy
Drug: Zidesamtinib (NVL-520)
ROS1+ NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy
Drug: Zidesamtinib (NVL-520)
ROS1+ NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy
Drug: Zidesamtinib (NVL-520)
ROS1+ solid tumor and progressed on any prior therapy
Drug: Zidesamtinib (NVL-520)
Oral tablet of zidesamtinib (NVL-520)
Maximum Tolerated Dose (MTD) (Phase 1)
Highest dose with dose-limiting toxicity (DLT) rate ≤ 25%
Time frame: Within 28 days of last patient dosed during dose escalation
Recommended Phase 2 Dose (RP2D)
To determine the RP2D
Time frame: Within 28 days of last patient dosed during dose escalation.
Objective Response Rate (ORR) (Phase 2)
To determine ORR as assessed by BICR
Time frame: 2-3 years after first patient dosed.
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, v5.0
Incidence and severity of treatment-emergent adverse events (TEAEs)
Time frame: Approximately 3 years.
Maximum plasma concentration (Cmax) of NVL-520
To determine the maximum plasma concentration (Cmax) of NVL-520
Time frame: Pre-dose and up to 24 hours post-dose
Plasma concentration at the end of the dosing interval (Ctau) of NVL-520
To determine the plasma concentration at the end of the dosing interval (Ctau) of NVL-520
Time frame: Pre-dose and up to 24 hours post-dose
Average plasma concentration (Cavg) of NVL-520
To determine the average plasma concentration (Cavg) of NVL-520
Time frame: Pre-dose and up to 24 hours post-dose
Time of maximum concentration (Tmax) of NVL-520
To determine the time of maximum concentration (Tmax) of NVL-520
Time frame: Pre-dose and up to 24 hours post-dose
Area under the curve at the end of the dosing interval (AUCtau) of NVL-520
To determine the area under the curve at the end of the dosing interval (AUCtau) of NVL-520
Time frame: Pre-dose and up to 24 hours post-dose
Area under the curve from time 0 to 24 (AUC0-24) of NVL-520
To determine the area under the curve from time 0 to 24 (AUC0-24) of NVL-520
Time frame: Pre-dose and up to 24 hours post-dose
Area under the curve from time 0 to infinity (AUCinf) of NVL-520
To determine the area under the curve from time 0 to infinity (AUCinf) of NVL-520
Time frame: Pre-dose and up to 24 hours post-dose
Oral clearance (CL/F) of NVL-520
To determine the oral clearance (CL/F) of NVL-520
Time frame: Pre-dose and up to 24 hours post-dose
Volume of distribution (Vz/F) of NVL-520
To determine the volume of distribution (Vz/F) of NVL-520
Time frame: Pre-dose and up to 24 hours post-dose
Half-life (t1/2) of NVL-520
To determine the half-life (t1/2) of NVL-520
Time frame: Pre-dose and up to 24 hours post-dose
Objective response rate (ORR)
Determine ORR as assessed by BICR
Time frame: 2-3 years after first patient dosed
Duration of response (DOR)
Determine DOR of NVL-520 until radiographic disease progression or death
Time frame: 2-3 years after first patient dosed
Clinical benefit rate (CBR)
Determine CBR of NVL-520
Time frame: 2-3 years after first patient dosed
Time to response
Determine time to response of NVL-520
Time frame: 2-3 years after first patient dosed
Progression-free survival (PFS)
Determine PFS of NVL-520 until radiographic disease progression or death
Time frame: Approximately 3 years
Overall survival (OS)
Determine OS
Time frame: Approximately 3 years
Rate of CNS progression
The incidence of CNS as first site of progression, alone or with concurrent extra-CNS progression
Time frame: Approximately 3 years
Intracranial objective response rate (IC-ORR)
Determine the intracranial objective response rate
Time frame: Approximately 3 years
Quality of life assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
EORTC QLQ-C30 measures cancer patients' physical, psychological, and social functions. Scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much." Higher score for the functioning scales and global health status denotes a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.
Time frame: 2-3 years after first patient dosed
Quality of life assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 module (EORTC QLQ-LC29)
EORTC-QLQ-LC29 measures the quality of life in patients with lung cancer. Symptom scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much." For symptoms scales, higher scores indicated greater symptom burden.
Time frame: 2-3 years after first patient dosed
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