A Study of NVL-520 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)

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ClinicalTrials.gov Identifier: NCT05118789

Recruitment Status : Recruiting

First Posted : November 12, 2021

Last Update Posted : March 28, 2023

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Nuvalent Inc.

Tracking Information

First Submitted Date ^ICMJE

October 19, 2021

First Posted Date ^ICMJE

November 12, 2021

Last Update Posted Date

March 28, 2023

Actual Study Start Date ^ICMJE

January 4, 2022

Estimated Primary Completion Date

October 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Dose limiting toxicities (DLTs) (Phase 1) [ Time Frame: Within the first 28 days of the first NVL-520 dose ]
Define the dose limiting toxicities (DLTs)
Recommended Phase 2 Dose (RP2D) [ Time Frame: Within 28 days of last patient dosed during dose escalation. ]
To determine the RP2D
Objective Response Rate (ORR) (Phase 2) [ Time Frame: 2-3 years after first patient dosed. ]
To determine ORR as assessed by BICR

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

Number of participants with treatment-emergent adverse events, as assessed by CTCAE, v5.0 [ Time Frame: Approximately 3 years. ]
Incidence and severity of treatment-emergent adverse events (TEAEs)
Maximum plasma concentration (Cmax) of NVL-520 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
To determine the maximum plasma concentration (Cmax) of NVL-520
Plasma concentration at the end of the dosing interval (Ctau) of NVL-520 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
To determine the plasma concentration at the end of the dosing interval (Ctau) of NVL-520
Average plasma concentration (Cavg) of NVL-520 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
To determine the average plasma concentration (Cavg) of NVL-520
Time of maximum concentration (Tmax) of NVL-520 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
To determine the time of maximum concentration (Tmax) of NVL-520
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 ]
To determine the area under the curve at the end of the dosing interval (AUCtau) of NVL-520
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 ]
To determine the area under the curve from time 0 to 24 (AUC0-24) of NVL-520
Area under the curve from time 0 to infinity (AUCinf) of NVL-520 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
To determine the area under the curve from time 0 to infinity (AUCinf) of NVL-520
Oral clearance (CL/F) of NVL-520 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
To determine the oral clearance (CL/F) of NVL-520
Volume of distribution (Vz/F) of NVL-520 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
To determine the volume of distribution (Vz/F) of NVL-520
Half-life (t1/2) of NVL-520 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
To determine the half-life (t1/2) of NVL-520
Objective response rate (ORR) [ Time Frame: 2-3 years after first patient dosed ]
Determine ORR as assessed by BICR
Duration of response (DOR) [ Time Frame: 2-3 years after first patient dosed ]
Determine DOR of NVL-520 until radiographic disease progression or death
Clinical benefit rate (CBR) [ Time Frame: 2-3 years after first patient dosed ]
Determine CBR of NVL-520
Time to response [ Time Frame: Approximately 3 years ]
Determine time to response of NVL-520
Progression-free survival (PFS) [ Time Frame: 2-3 years after first patient dosed ]
Determine PFS of NVL-520 until radiographic disease progression or death
Overall survival (OS) [ Time Frame: Approximately 3 years ]
Determine OS

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

A Study of NVL-520 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)

Official Title ^ICMJE

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

Brief Summary

Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of 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 NVL-520 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 NVL-520 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 NVL-520 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.
Cohort 2b: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and no prior platinum-based chemotherapy with or without 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 platinum-based chemotherapy with or without immunotherapy.
Cohort 2e: ROS1-positive solid tumor and progressed on any prior therapy.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1
Phase 2

Study Design ^ICMJE

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Locally Advanced Solid Tumor
Metastatic Solid Tumor

Intervention ^ICMJE

Drug: NVL-520

Oral tablet of NVL-520

Study Arms ^ICMJE

Experimental: Phase 1 dose escalation
NVL-520 oral daily dosing

Intervention: Drug: NVL-520
Experimental: Cohort 2a
ROS1+ NSCLC naïve to TKI therapy

Intervention: Drug: NVL-520
Experimental: Cohort 2b
ROS1+ NSCLC treated with 1 prior ROS1 TKI and no prior platinum-based chemotherapy or immunotherapy

Intervention: Drug: NVL-520
Experimental: Cohort 2c
ROS1+ NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy

Intervention: Drug: NVL-520
Experimental: Cohort 2d
ROS1+ NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior platinum-based chemotherapy with or without immunotherapy

Intervention: Drug: NVL-520
Experimental: Cohort 2e
ROS1+ solid tumor and progressed on any prior therapy

Intervention: Drug: NVL-520

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

247

Original Estimated Enrollment ^ICMJE

246

Estimated Study Completion Date ^ICMJE

October 31, 2026

Estimated Primary Completion Date

October 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Age ≥18 years (Cohort 2e only: Age ≥12 years and weighing>40 kg).
Phase 1:
1. Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement.
2. Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement.
3. Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (other than NSCLC) with ROS1 rearrangement.
Prior anticancer treatment (except cohort 2a).
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.
Adequate baseline organ function and bone marrow reserve.

Exclusion Criteria:

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.
Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

12 Years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Nuvalent

857-357-7000

clinicaltrials@nuvalent.com

Listed Location Countries ^ICMJE

Australia, France, Netherlands, Spain, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT05118789

Other Study ID Numbers ^ICMJE

NVL-520-01

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Not Provided

Current Responsible Party

Nuvalent Inc.

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Nuvalent Inc.

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Viola Zhu, MD, PhD

Nuvalent Inc.

PRS Account

Nuvalent Inc.

Verification Date

March 2023

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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