TriangleNCT05118789 · CITED IN SOURCE DOCUMENTS
A Study of Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE1, PHASE2
- Status at capture
- RECRUITING
- Registry last update
- 2025-10-24
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility Criteria
- Inclusion Criteria: 1. Age ≥18 years (Cohort 2e only: Age ≥12 years). 2. Disease Criteria: 1. Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement. 2. Phase 2: Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement. 3. Phase 2: Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (other than NSCLC) with ROS1 rearrangement. 3. Prior anticancer treatment (except cohort 2a). 4. Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1. Phase 2: Must have measurable disease according to RECIST 1.1. 5. Adequate baseline organ function and bone marrow reserve. Exclusion Criteria: 1. Patient's cancer has a known oncogenic driver alteration other than ROS1. 2. Known allergy/hypersensitivity to excipients of NVL-520. 3. Major surgery within 4 weeks of first dose of study drug. 4. Ongoing anticancer therapy. 5. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.
- healthy Volunteers
- false
- minimum Age
- 12 Years
- sex
- ALL
- std Ages
- CHILD
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Zidesamtinib (NVL-520) oral daily dosing
- intervention Names
- Drug: Zidesamtinib (NVL-520)
- label
- Phase 1 dose escalation
- type
- EXPERIMENTAL
- description
- ROS1+ NSCLC naïve to TKI therapy and up to 1 prior chemotherapy and/or immunotherapy
- intervention Names
- Drug: Zidesamtinib (NVL-520)
- label
- Cohort 2a
- type
- EXPERIMENTAL
- description
- ROS1+ NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy
- intervention Names
- Drug: Zidesamtinib (NVL-520)
- label
- Cohort 2b
- type
- EXPERIMENTAL
- description
- ROS1+ NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy
- intervention Names
- Drug: Zidesamtinib (NVL-520)
- label
- Cohort 2c
- type
- EXPERIMENTAL
- description
- ROS1+ NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy
- intervention Names
- Drug: Zidesamtinib (NVL-520)
- label
- Cohort 2d
- type
- EXPERIMENTAL
- description
- ROS1+ solid tumor and progressed on any prior therapy
- intervention Names
- Drug: Zidesamtinib (NVL-520)
- label
- Cohort 2e
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Cohort 2a
- Cohort 2b
- Cohort 2c
- Cohort 2d
- Cohort 2e
- Phase 1 dose escalation
- description
- Oral tablet of zidesamtinib (NVL-520)
- name
- Zidesamtinib (NVL-520)
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- SEQUENTIAL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 359
- type
- ESTIMATED
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Highest dose with dose-limiting toxicity (DLT) rate ≤ 25%
- measure
- Maximum Tolerated Dose (MTD) (Phase 1)
- time Frame
- Within 28 days of last patient dosed during dose escalation
- description
- To determine the RP2D
- measure
- Recommended Phase 2 Dose (RP2D)
- time Frame
- Within 28 days of last patient dosed during dose escalation.
- description
- To determine ORR as assessed by BICR
- measure
- Objective Response Rate (ORR) (Phase 2)
- time Frame
- 2-3 years after first patient dosed.
- secondary Outcomes
- description
- Incidence and severity of treatment-emergent adverse events (TEAEs)
- measure
- Number of participants with treatment-emergent adverse events, as assessed by CTCAE, v5.0
- time Frame
- Approximately 3 years.
- description
- To determine the maximum plasma concentration (Cmax) of NVL-520
- measure
- Maximum plasma concentration (Cmax) of NVL-520
- time Frame
- Pre-dose and up to 24 hours post-dose
- description
- To determine the plasma concentration at the end of the dosing interval (Ctau) of NVL-520
- measure
- Plasma concentration at the end of the dosing interval (Ctau) of NVL-520
- time Frame
- Pre-dose and up to 24 hours post-dose
- description
- To determine the average plasma concentration (Cavg) of NVL-520
- measure
- Average plasma concentration (Cavg) of NVL-520
- time Frame
- Pre-dose and up to 24 hours post-dose
- description
- To determine the time of maximum concentration (Tmax) of NVL-520
- measure
- Time of maximum concentration (Tmax) of NVL-520
- time Frame
- Pre-dose and up to 24 hours post-dose
- description
- To determine the area under the curve at the end of the dosing interval (AUCtau) of NVL-520
- measure
- 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
- description
- To determine the area under the curve from time 0 to 24 (AUC0-24) of NVL-520
- measure
- 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
- description
- To determine the area under the curve from time 0 to infinity (AUCinf) of NVL-520
- measure
- Area under the curve from time 0 to infinity (AUCinf) of NVL-520
- time Frame
- Pre-dose and up to 24 hours post-dose
- description
- To determine the oral clearance (CL/F) of NVL-520
- measure
- Oral clearance (CL/F) of NVL-520
- time Frame
- Pre-dose and up to 24 hours post-dose
- description
- To determine the volume of distribution (Vz/F) of NVL-520
- measure
- Volume of distribution (Vz/F) of NVL-520
- time Frame
- Pre-dose and up to 24 hours post-dose
- description
- To determine the half-life (t1/2) of NVL-520
- measure
- Half-life (t1/2) of NVL-520
- time Frame
- Pre-dose and up to 24 hours post-dose
- description
- Determine ORR as assessed by BICR
- measure
- Objective response rate (ORR)
- time Frame
- 2-3 years after first patient dosed
Full study description
- brief Summary
- 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.
- detailed Description
- In Phase 2, study patients will be enrolled into 5 distinct expansion cohorts: * Cohort 2a: ROS1-positive NSCLC naïve to Tyrosine Kinase Inhibitor (TKI) therapy and up to 1 prior chemotherapy and/or immunotherapy. * Cohort 2b: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy. * Cohort 2c: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy. * Cohort 2d: ROS1-positive NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy. * Cohort 2e: ROS1-positive solid tumor and progressed on any prior therapy.
Source references
Source notices and limitations
Discovery and provenance
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- 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.
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- ation for Jideytro will be posted on <a href="https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm">Drugs@FDA</a></p><p>Efficacy was evaluated in ARROS-1 (NCT05118789), a multicenter, single-arm, open-label, multi-cohort trial in patients with previously treated locally advanced or metastatic ROS1-positive NSCLC. The efficac
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- FDA approves zidesamtinib for ROS1-positive non-small cell lung cancer
Preserved source evidence · Not medical advice