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

NCT05118789
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
359
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Lead sponsor
Nuvalent Inc.
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Start date
2022-01-04
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Number of sites
63
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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.
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Short title
A Study of Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)
clinicaltrials.gov
Official title
A Phase 1/2 Study of the Highly Selective ROS1 Inhibitor Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors (ARROS-1)
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2028-12-31
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First posted
2021-11-12
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Registry last updated
2025-10-24
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Primary completion date
2027-12-31
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Start date
2022-01-04
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Participants
359
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Participant count basis
Estimated
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Planned participants
359
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Protocol amendments
5
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Number of sites
63
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Nuvalent Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05118789
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ClinicalTrials.gov ID
NCT05118789
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Maximum Tolerated Dose (MTD) (Phase 1)

    Timeframe: Within 28 days of last patient dosed during dose escalation

    Highest dose with dose-limiting toxicity (DLT) rate ≤ 25%

  2. Recommended Phase 2 Dose (RP2D)

    Timeframe: Within 28 days of last patient dosed during dose escalation.

    To determine the RP2D

  3. Objective Response Rate (ORR) (Phase 2)

    Timeframe: 2-3 years after first patient dosed.

    To determine ORR as assessed by BICR

  1. Number of participants with treatment-emergent adverse events, as assessed by CTCAE, v5.0

    Timeframe: Approximately 3 years.

    Incidence and severity of treatment-emergent adverse events (TEAEs)

  2. Maximum plasma concentration (Cmax) of NVL-520

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the maximum plasma concentration (Cmax) of NVL-520

  3. Plasma concentration at the end of the dosing interval (Ctau) of NVL-520

    Timeframe: 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

  4. Average plasma concentration (Cavg) of NVL-520

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the average plasma concentration (Cavg) of NVL-520

  5. Time of maximum concentration (Tmax) of NVL-520

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the time of maximum concentration (Tmax) of NVL-520

  6. Area under the curve at the end of the dosing interval (AUCtau) of NVL-520

    Timeframe: 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

  7. Area under the curve from time 0 to 24 (AUC0-24) of NVL-520

    Timeframe: 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

  8. Area under the curve from time 0 to infinity (AUCinf) of NVL-520

    Timeframe: 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

  9. Oral clearance (CL/F) of NVL-520

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the oral clearance (CL/F) of NVL-520

  10. Volume of distribution (Vz/F) of NVL-520

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the volume of distribution (Vz/F) of NVL-520

  11. Half-life (t1/2) of NVL-520

    Timeframe: Pre-dose and up to 24 hours post-dose

    To determine the half-life (t1/2) of NVL-520

  12. Objective response rate (ORR)

    Timeframe: 2-3 years after first patient dosed

    Determine ORR as assessed by BICR

  13. Duration of response (DOR)

    Timeframe: 2-3 years after first patient dosed

    Determine DOR of NVL-520 until radiographic disease progression or death

  14. Clinical benefit rate (CBR)

    Timeframe: 2-3 years after first patient dosed

    Determine CBR of NVL-520

  15. Time to response

    Timeframe: 2-3 years after first patient dosed

    Determine time to response of NVL-520

  16. Progression-free survival (PFS)

    Timeframe: Approximately 3 years

    Determine PFS of NVL-520 until radiographic disease progression or death

  17. Overall survival (OS)

    Timeframe: Approximately 3 years

    Determine OS

  18. Rate of CNS progression

    Timeframe: Approximately 3 years

    The incidence of CNS as first site of progression, alone or with concurrent extra-CNS progression

  19. Intracranial objective response rate (IC-ORR)

    Timeframe: Approximately 3 years

    Determine the intracranial objective response rate

  20. Quality of life assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

    Timeframe: 2-3 years after first patient dosed

    EORTC QLQ-C30 measures cancer patients' physical, psychological, and social functions. Scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much." Higher score for the functioning scales and global health status denotes a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.

  21. 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)

    Timeframe: 2-3 years after first patient dosed

    EORTC-QLQ-LC29 measures the quality of life in patients with lung cancer. Symptom scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much." For symptoms scales, higher scores indicated greater symptom burden.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Children, Adults, Older adults
Minimum age
12 Years
Healthy volunteers
No

  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.

  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.
Sources for eligibility
clinicaltrials.gov

  • UCI Medical CenterOrange, United StatesRecruiting
  • Stanford MedicinePalo Alto, United StatesRecruiting
  • UC Davis Comprehensive Cancer CenterSacramento, United StatesRecruiting
  • University of Colorado Cancer CenterDenver, United StatesRecruiting
  • Georgetown University Medical CenterWashington D.C., United StatesRecruiting
  • University of MiamiCoral Gables, United StatesRecruiting
  • University of ChicagoChicago, United StatesRecruiting
  • Mass General HospitalBoston, United StatesRecruiting
  • Dana-Farber Cancer InstituteBoston, United StatesRecruiting
  • Henry Ford Cancer InstituteDetroit, United StatesRecruiting
  • Washington University School of MedicineSt Louis, United StatesRecruiting
  • NYU Langone HealthNew York, United StatesRecruiting
  • Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting
  • Atrium Health Levine Cancer InstituteCharlotte, United StatesRecruiting
  • Ohio State UniversityColumbus, United StatesRecruiting
  • Fox Chase Cancer CenterPhiladelphia, United StatesRecruiting
  • Sarah Cannon Research InstituteNashville, United StatesRecruiting
  • MD Anderson Cancer CenterHouston, United StatesActive, not recruiting
  • NEXT Oncology - Virginia Cancer SpecialistsFairfax, United StatesRecruiting
  • University of Washington / Fred Hutchinson Cancer CenterSeattle, United StatesRecruiting
  • Chris O'Brien LifehouseCamperdown, AustraliaRecruiting
  • Peter MacCallum Cancer CentreMelbourne, AustraliaRecruiting
  • University Hospital LeuvenLeuven, BelgiumRecruiting
  • Cross Cancer InstituteEdmonton, CanadaRecruiting
  • Princess Margaret Cancer ResearchToronto, CanadaRecruiting

And 38 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)