A Study of Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age12+
SponsorNuvalent Inc.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years (Cohort 2e only: Age ≥12 years).
Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement.
Phase 2: Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement.
Phase 2: Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (other than NSCLC) with ROS1 rearrangement.
Disqualifiers
Patient's cancer has a known oncogenic driver alteration other than ROS1.
Known allergy/hypersensitivity to excipients of NVL-520.
Major surgery within 4 weeks of first dose of study drug.
Ongoing anticancer therapy.
Trial design
Design model
Sequential
Treatments tested in this trial
Zidesamtinib (NVL-520)
DrugOral tablet of zidesamtinib (NVL-520)
Treatment groups
359 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Phase 1 dose escalationExperimental treatment 1 intervention
Group B: Cohort 2aExperimental treatment 1 intervention
Group C: Cohort 2bExperimental treatment 1 intervention
Group D: Cohort 2cExperimental treatment 1 intervention
Group E: Cohort 2dExperimental treatment 1 intervention
Group F: Cohort 2eExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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 escalation2
Recommended Phase 2 Dose (RP2D)
To determine the RP2D
Time frame
Within 28 days of last patient dosed during dose escalation.3
Objective Response Rate (ORR) (Phase 2)
To determine ORR as assessed by BICR
Time frame
2-3 years after first patient dosed.Secondary outcomes
1
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.2
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-dose3
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-dose4
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-doseSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov