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

Sponsor: Nuvalent Inc.

Sponsor score: 60
Inactive

ClinicalTrials ID:NCT05118789

Patient View

The ARROS-1 trial evaluates NVL-520, an oral tablet, in advanced ROS1-positive NSCLC and solid tumors. Phase 1 focuses on dose determination, while Phase 2 assesses efficacy across five cohorts based on prior treatments. Eligibility includes adults with confirmed ROS1 rearrangements, measurable disease, and adequate organ function. Cohort 2e includes patients aged 12 and older.

Patient Parameters

Program Overview

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.

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 and up to 1 prior chemotherapy and/or immunotherapy.
  • Cohort 2b: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or 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 chemotherapy and/or immunotherapy.
  • Cohort 2e: ROS1-positive solid tumor and progressed on any prior therapy.

Eligibility Criteria

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.

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.

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