A study with NVL-520, an inhibitor of ROS1 protein, in patients with advanced Non-Small Cell Lung Cancer and other solid tumors that are ROS1-positiv.

A Phase 1/2 Study of the Highly Selective ROS1 Inhibitor NVL-520 in Patients with Advanced NSCLC and Other Solid Tumors (ARROS-1)

Status

Not yet recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-002477-26-ES

Enrollment

246

Registered

2021-08-26

Start date

2021-11-26

Completion date

Unknown

Last updated

2021-12-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Non-Small Cell Lung Cancer (NSCLC)and Other Solid Tumors with ROS1+ rearrangement

Interventions

Product Name: NVL-520 Product Code: NVL-520 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: NVL-520 Current Sponsor code: NVL-520 Other descriptive name: NVL-520 Concentration unit: mg mi

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Patients must meet all of the following criteria to be eligible to enroll in the study: 1. Age > or =18 years (Cohort 2e only: Age > or =12 years and weighing>40 kg). 2. Phase 1: a. Histologically or cytologically confirmed metastatic solid tumor with documented ROS1 rearrangement b. Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed metastatic NSCLC with ROS1 rearrangement c. Cohort 2e: Histologically or cytologically confirmed metastatic solid tumor (other than NSCLC) with ROS1 rearrangement 3. Must have received Prior anticancer treatment (except for cohort 2a) 4. Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1. Phase 2: Must have measurable disease, defined as =1 radiologically measurable target lesion according to RECIST 1.1. In all study parts, patients with asymptomatic CNS-only measurable disease =10 mm as defined by RECIST 1.1 are eligible. 5. Adequate baseline organ function and bone marrow reserve Are the trial subjects under 18? yes Number of subjects for this age range: 3 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80

Exclusion criteria

Exclusion criteria: 1. Patient’s cancer has a known primary driver alteration other than ROS1. 2. Known allergy/hypersensitivity to excipients of NVL-520. 3. Major surgery within 4 weeks of study entry. 4. Ongoing or recent anticancer therapy 5. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study

Design outcomes

Primary

Measure	Time frame
Main Objective: Phase 1 Primary Objective • To determine the RP2D and/or maximum tolerated dose (MTD) of NVL-520 in patients with advanced ROS1-positive solid tumors Phase 2 Primary Objective • To evaluate the ORR of NVL-520 at the RP2D in patients with advanced ROS1-positive NSCLC and other solid tumors;Secondary Objective: Phase 1 - Secondary Objectives • To evaluate the overall safety and tolerability of NVL-520 • To characterize the PK profile of NVL-520 • To evaluate preliminary antitumor activity of NVL-520 in patients with advanced ROS1 positive solid tumors Phase 2 - Secondary Objectives • To assess additional measures of clinical efficacy in patients with ROS1-positive NSCLC and other solid tumors • To evaluate the intracranial antitumor activity of NVL-520 at the RP2D in patients with advanced ROS1-positive NSCLC and other solid tumors • To characterize the safety and tolerability of NVL-520 at the RP2D • To confirm the PK profile of NVL-520 at the RP2D;Primary end point(s): Phase 1 • Incidence of dose-limiting toxicities (DLTs) during Cycle 1 Phase 2 • ORR per RECIST 1.1 - Defined as the proportion of patients with a confirmed CR or PR according to RECIST 1.1 per Blinded Independent Central Review (BICR);Timepoint(s) of evaluation of this end point: • DOR per RECIST 1.1 • CBR per RECIST 1.1 • Incidence and severity of TEAEs and changes in clinically relevant laboratory parameters • Pharmacokinetic parameters of NVL-520 - Cmax, Cmax - dose normalized, Ctau, Cavg, Tmax, AUCtau, AUCtau - dose normalized, AUC0-24, AUC0-24 – dose normalized, AUCinf, AUCinf – dose normalized, CL/F, Vz/F, t1/2 • PFS per RECIST 1.1 • Overall survival (OS)	—

Measure

Time frame

Main Objective: Phase 1 Primary Objective • To determine the RP2D and/or maximum tolerated dose (MTD) of NVL-520 in patients with advanced ROS1-positive solid tumors Phase 2 Primary Objective • To evaluate the ORR of NVL-520 at the RP2D in patients with advanced ROS1-positive NSCLC and other solid tumors;Secondary Objective: Phase 1 - Secondary Objectives • To evaluate the overall safety and tolerability of NVL-520 • To characterize the PK profile of NVL-520 • To evaluate preliminary antitumor activity of NVL-520 in patients with advanced ROS1 positive solid tumors Phase 2 - Secondary Objectives • To assess additional measures of clinical efficacy in patients with ROS1-positive NSCLC and other solid tumors • To evaluate the intracranial antitumor activity of NVL-520 at the RP2D in patients with advanced ROS1-positive NSCLC and other solid tumors • To characterize the safety and tolerability of NVL-520 at the RP2D • To confirm the PK profile of NVL-520 at the RP2D;Primary end point(s): Phase 1 • Incidence of dose-limiting toxicities (DLTs) during Cycle 1 Phase 2 • ORR per RECIST 1.1 - Defined as the proportion of patients with a confirmed CR or PR according to RECIST 1.1 per Blinded Independent Central Review (BICR);Timepoint(s) of evaluation of this end point: • DOR per RECIST 1.1 • CBR per RECIST 1.1 • Incidence and severity of TEAEs and changes in clinically relevant laboratory parameters • Pharmacokinetic parameters of NVL-520 - Cmax, Cmax - dose normalized, Ctau, Cavg, Tmax, AUCtau, AUCtau - dose normalized, AUC0-24, AUC0-24 – dose normalized, AUCinf, AUCinf – dose normalized, CL/F, Vz/F, t1/2 • PFS per RECIST 1.1 • Overall survival (OS)

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Secondary

Measure	Time frame
Secondary end point(s): Phase 1 • Incidence and severity of treatment-emergent adverse events (TEAEs) and changes in clinically relevant laboratory parameters • Pharmacokinetic parameters of NVL-520 - Maximum plasma concentration (Cmax); Cmax – dose normalized, plasma concentration at the end of the dosing interval (Ctau); average plasma concentration (Cavg); time of maximum concentration (Tmax); area under the curve at the end of the dosing interval (AUCtau); AUCtau – dose normalized, area under the curve from time 0 to 24 (AUC0-24); AUC0-24 – dose normalized, area under the curve from time 0 to infinity (AUCinf); AUCinf – dose normalized; oral clearance (CL/F); volume of distribution (Vz/F); and half-life (t1/2) • Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Phase 2 • DOR per RECIST 1.1 • CBR per RECIST 1.1 • Incidence and severity of TEAEs and changes in clinically relevant laboratory parameters • Pharmacokinetic parameters of NVL-520 - Cmax, Cmax - dose normalized, Ctau, Cavg, Tmax, AUCtau, AUCtau - dose normalized, AUC0-24, AUC0-24 – dose normalized, AUCinf, AUCinf –dose normalized, CL/F, Vz/F, t1/2 • PFS per RECIST 1.1 • Overall survival (OS);Timepoint(s) of evaluation of this end point: Table 1: Schedule of Assessments Phase 1 and Phase 2 (All Cohorts) Assessments/Procedures Table 2: Schedule of Pharmacokinetic Sampling Timepoints (Phase 1 and Phase 2)	—

Measure

Time frame

Secondary end point(s): Phase 1 • Incidence and severity of treatment-emergent adverse events (TEAEs) and changes in clinically relevant laboratory parameters • Pharmacokinetic parameters of NVL-520 - Maximum plasma concentration (Cmax); Cmax – dose normalized, plasma concentration at the end of the dosing interval (Ctau); average plasma concentration (Cavg); time of maximum concentration (Tmax); area under the curve at the end of the dosing interval (AUCtau); AUCtau – dose normalized, area under the curve from time 0 to 24 (AUC0-24); AUC0-24 – dose normalized, area under the curve from time 0 to infinity (AUCinf); AUCinf – dose normalized; oral clearance (CL/F); volume of distribution (Vz/F); and half-life (t1/2) • Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Phase 2 • DOR per RECIST 1.1 • CBR per RECIST 1.1 • Incidence and severity of TEAEs and changes in clinically relevant laboratory parameters • Pharmacokinetic parameters of NVL-520 - Cmax, Cmax - dose normalized, Ctau, Cavg, Tmax, AUCtau, AUCtau - dose normalized, AUC0-24, AUC0-24 – dose normalized, AUCinf, AUCinf –dose normalized, CL/F, Vz/F, t1/2 • PFS per RECIST 1.1 • Overall survival (OS);Timepoint(s) of evaluation of this end point: Table 1: Schedule of Assessments Phase 1 and Phase 2 (All Cohorts) Assessments/Procedures Table 2: Schedule of Pharmacokinetic Sampling Timepoints (Phase 1 and Phase 2)

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Countries

France, Netherlands, Spain, United States

Contacts

Public ContactGosia Riley

Nuvalent, Inc.

Griley@nuvalent.com1857357-7000

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026