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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05118789




Registration number
NCT05118789
Ethics application status
Date submitted
19/10/2021
Date registered
12/11/2021
Date last updated
8/03/2024

Titles & IDs
Public title
A Study of NVL-520 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)
Scientific title
A Phase 1/2 Study of the Highly Selective ROS1 Inhibitor NVL-520 in Patients With Advanced NSCLC and Other Solid Tumors (ARROS-1)
Secondary ID [1] 0 0
NVL-520-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Solid Tumor 0 0
Metastatic Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NVL-520

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

Experimental: Cohort 2a - ROS1+ NSCLC naïve to TKI therapy and up to 1 prior chemotherapy and/or immunotherapy

Experimental: Cohort 2b - ROS1+ NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy

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

Experimental: Cohort 2d - ROS1+ NSCLC treated with =2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy

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


Treatment: Drugs: NVL-520
Oral tablet of NVL-520
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD) (Phase 1)
Timepoint [1] 0 0
Within 28 days of last patient dosed during dose escalation
Primary outcome [2] 0 0
Recommended Phase 2 Dose (RP2D)
Timepoint [2] 0 0
Within 28 days of last patient dosed during dose escalation.
Primary outcome [3] 0 0
Objective Response Rate (ORR) (Phase 2)
Timepoint [3] 0 0
2-3 years after first patient dosed.
Secondary outcome [1] 0 0
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, v5.0
Timepoint [1] 0 0
Approximately 3 years.
Secondary outcome [2] 0 0
Maximum plasma concentration (Cmax) of NVL-520
Timepoint [2] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [3] 0 0
Plasma concentration at the end of the dosing interval (Ctau) of NVL-520
Timepoint [3] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [4] 0 0
Average plasma concentration (Cavg) of NVL-520
Timepoint [4] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [5] 0 0
Time of maximum concentration (Tmax) of NVL-520
Timepoint [5] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [6] 0 0
Area under the curve at the end of the dosing interval (AUCtau) of NVL-520
Timepoint [6] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [7] 0 0
Area under the curve from time 0 to 24 (AUC0-24) of NVL-520
Timepoint [7] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [8] 0 0
Area under the curve from time 0 to infinity (AUCinf) of NVL-520
Timepoint [8] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [9] 0 0
Oral clearance (CL/F) of NVL-520
Timepoint [9] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [10] 0 0
Volume of distribution (Vz/F) of NVL-520
Timepoint [10] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [11] 0 0
Half-life (t1/2) of NVL-520
Timepoint [11] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [12] 0 0
Objective response rate (ORR)
Timepoint [12] 0 0
2-3 years after first patient dosed
Secondary outcome [13] 0 0
Duration of response (DOR)
Timepoint [13] 0 0
2-3 years after first patient dosed
Secondary outcome [14] 0 0
Clinical benefit rate (CBR)
Timepoint [14] 0 0
2-3 years after first patient dosed
Secondary outcome [15] 0 0
Time to response
Timepoint [15] 0 0
2-3 years after first patient dosed
Secondary outcome [16] 0 0
Progression-free survival (PFS)
Timepoint [16] 0 0
Approximately 3 years
Secondary outcome [17] 0 0
Overall survival (OS)
Timepoint [17] 0 0
Approximately 3 years
Secondary outcome [18] 0 0
Rate of CNS progression
Timepoint [18] 0 0
Approximately 3 years
Secondary outcome [19] 0 0
Intracranial objective response rate (IC-ORR)
Timepoint [19] 0 0
Approximately 3 years
Secondary outcome [20] 0 0
Quality of life assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Timepoint [20] 0 0
2-3 years after first patient dosed
Secondary outcome [21] 0 0
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)
Timepoint [21] 0 0
2-3 years after first patient dosed

Eligibility
Key inclusion criteria
1. Age =18 years (Cohort 2e only: Age =12 years and weighing>40 kg).

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.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/01/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/10/2026
Actual
Sample size
Target
359
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Belgium
State/province [15] 0 0
Leuven
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
France
State/province [18] 0 0
Lyon
Country [19] 0 0
France
State/province [19] 0 0
Nantes
Country [20] 0 0
France
State/province [20] 0 0
Toulouse
Country [21] 0 0
France
State/province [21] 0 0
Villejuif
Country [22] 0 0
Germany
State/province [22] 0 0
Cologne
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Gyeonggi-do
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Seoul
Country [25] 0 0
Netherlands
State/province [25] 0 0
Amsterdam
Country [26] 0 0
Netherlands
State/province [26] 0 0
Groningen
Country [27] 0 0
Singapore
State/province [27] 0 0
Singapore
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Coruna
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Taiwan
State/province [31] 0 0
Taichung
Country [32] 0 0
Taiwan
State/province [32] 0 0
Tainan
Country [33] 0 0
Taiwan
State/province [33] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Nuvalent Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05118789
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Vivek Upadhyay, MD, MBI
Address 0 0
Nuvalent Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Nuvalent
Address 0 0
Country 0 0
Phone 0 0
857-357-7000
Fax 0 0
Email 0 0
clinicaltrials@nuvalent.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05118789